Measuring the impact of the Capital Card®, a novel form of contingency management, on substance misuse treatment outcomes:A retrospective evaluation

Background The Capital Card, developed by WDP, is a digital innovation which acts as a form of contingency management, and aims to significantly improve service user outcomes. WDP is a substance misuse treatment provider commissioned by local authorities across the UK to support service users and their families affected by addiction. The Capital Card, much like commercial loyalty cards, uses a simple earn-spend points system which incentivises and rewards service users for engaging with services e.g. by attending key work sessions, Blood Borne Virus appointments or group-work sessions. The Spend activities available to service users are designed to improve overall wellbeing and build social and recovery capital, and include activities such as educational classes, fitness classes, driving lessons, and cinema tickets. Methods and findings We compared successful completion rates of 1,545 service users accessing one of WDP’s London based community services over a two-year period; before and after the Capital Card was introduced. Client demographics (age, sex and primary substance) were controlled for during the analysis. Once client demographics were controlled for, analysis showed that clients with a Capital Card were 1.5 times more likely to successfully complete treatment than those who had not had the Capital Card (OR = 1.507, 95% CI = 1.194 to 1.902). Conclusions The results of this initial evaluation are of particular interest to commissioners and policy makers as it indicates that the Capital Card can be used effectively as a form of contingency management to enhance recovery outcomes for service users engaging in community-based substance misuse services

Antidepressant use and risk of adverse outcomes in people aged 20–64 years: cohort study using a primary care database

Background: Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20–64 years diagnosed with depression. Methods: We conducted a cohort study in 238,963 patients aged 20–64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables. Results: During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21–1.39) and other antidepressants (1.28, 1.11–1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25–1.88) and other antidepressants (1.61, 1.22–2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22–1.59) and other antidepressants (1.26, 1.08–1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up. Conclusions: Selective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made

Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression. Design Cohort study. Setting Patients registered with UK general practices contributing data to the QResearch database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables. Main outcome measures Suicide and attempted suicide or self harm during follow-up. Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment. Conclusion Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these period

Antidepressant use and risk of adverse outcomes in older people: population based cohort study

Objectives To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose

Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database

Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years’ follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years’ follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years’ follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥40 mg/day). Conclusions This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine

Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans.

Protein disulfide isomerase (PDI) is a multifunctional protein required for many aspects of protein folding and transit through the endoplasmic reticulum. A conserved family of three PDIs have been functionally analysed using genetic mutants of the model organism Caenorhabditis elegans. PDI-1 and PDI-3 are individually nonessential, whereas PDI-2 is required for normal post-embryonic development. In combination, all three genes are synergistically essential for embryonic development in this nematode. Mutations in pdi-2 result in severe body morphology defects, uncoordinated movement, adult sterility, abnormal molting and aberrant collagen deposition. Many of these phenotypes are consistent with a role in collagen biogenesis and extracellular matrix formation. PDI-2 is required for the normal function of prolyl 4-hydroxylase, a key collagen-modifying enzyme. Site-directed mutagenesis indicates that the independent catalytic activity of PDI-2 may also perform an essential developmental function. PDI-2 therefore performs two critical roles during morphogenesis. The role of PDI-2 in collagen biogenesis can be partially restored following complementation of the mutant with human PDI

Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in <i>Caenorhabditis elegans</i>

The nematode cuticle is a protective collagenous extracellular matrix that is modified, cross-linked, and processed by a number of key enzymes. This Ecdysozoan-specific structure is synthesized repeatedly and allows growth and development in a linked degradative and biosynthetic process known as molting. A targeted RNA interference screen using a cuticle collagen marker has been employed to identify components of the cuticle biosynthetic pathway. We have characterized an essential peroxidase, MoLT-7 (MLT-7), that is responsible for proper cuticle molting and re-synthesis. MLT-7 is an active, inhibitable peroxidase that is expressed in the cuticle-synthesizing hypodermis coincident with each larval molt. mlt-7 mutants show a range of body morphology defects, most notably molt, dumpy, and early larval stage arrest phenotypes that can all be complemented with a wild type copy of mlt-7. The cuticles of these mutants lacks di-tyrosine cross-links, becomes permeable to dye and accessible to tyrosine iodination, and have aberrant collagen protein expression patterns. Overexpression of MLT-7 causes mutant phenotypes further supporting its proposed enzymatic role. In combination with BLI-3, an H2O2-generating NADPH dual oxidase, MLT-7 is essential for post-embryonic development. Disruption of mlt-7, and particularly bli-3, via RNA interference also causes dramatic changes to the in vivo cross-linking patterns of the cuticle collagens DPY-13 and COL-12. This points toward a functionally cooperative relationship for these two hypodermally expressed proteins that is essential for collagen cross-linking and proper extracellular matrix formation

Aspects of alcohol use disorder affecting social cognition as assessed using the Mini Social and Emotional Assessment (mini-SEA)

Background Alcohol Use Disorder (AUD) is associated with problems with processing complex social scenarios. Little is known about the relationship between distinct AUD-related factors (e.g., years of problematic drinking), aspects of cognitive function and dysfunction in individuals diagnosed with AUD, and the relative impact these may have on social cognition. Aims To explore differences in social cognition between a group of participants diagnosed with AUD and controls, using a clinical measure, the Mini Social and Emotional Assessment (mini-SEA). The mini-SEA was used to evaluate social and emotional understanding through a facial emotional recognition task and by utilising a series of social scenes some of which contain a faux pas (social error). Methods Eighty-five participants (individuals with AUD and controls) completed demographic questions and a general cognitive and social cognitive test battery over three consecutive days. Results Between group analyses revealed that the participants with AUD performed less well on the faux pas test, and differences were also revealed in the emotional facial recognition task. Years of problematic alcohol consumption was the strongest predictor of poor ToM reasoning. Conclusion These results suggest a strong link between AUD chronicity and social cognition, though the direction of this relationship needs further elucidation. This may be of clinical relevance to abstinence and relapse management, as basic social cognition skills and ability to maintain interpersonal relationships are likely to be crucial to recovery