Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

BACKGROUND: Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. METHODS: From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. RESULTS: Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. CONCLUSIONS: While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders.

Prevalence and incidence rates of cardiovascular, autoimmune, and other diseases in patients with psoriatic or psoriatic arthritis: a retrospective study using Clinical Practice Research Datalink.

BACKGROUND: Previous studies have demonstrated that patients with psoriasis have higher rates of comorbidities compared to the general population. Despite the clinical and economic burden of psoriatic disease, there have been few large-scale observational studies focused on this condition. OBJECTIVE: To assess rates of cardiovascular, autoimmune, infectious and other conditions in patients with psoriasis or psoriatic arthritis (PSA). METHODS: The data for this retrospective study were obtained from the Clinical Practice Research Datalink (CRPD). Cohorts of patients with psoriasis (n = 27,672; mild, n = 22,174, severe, n = 5498) and PSA (n = 1952) were generated based on the diagnosis made by general practitioner or specialist recorded in CPRD between 2006 and 2010. Frequencies of comorbidities at baseline and incidence rate ratios (IRR) of medical conditions occurring during follow-up were calculated and compared between groups. Cox proportional hazard models were employed to compare hazard ratios (HR) of comorbidities across the same subpopulations previously described. RESULTS: Significant differences in the unadjusted risk of cardiovascular disease, hyperlipidaemia, diabetes, skin cancer and autoimmune diseases were observed between patients with differing severity of psoriasis or between PSA and psoriasis patients. The adjusted HR analyses confirmed patients with severe psoriasis had significantly higher rates of several conditions including diabetes (1.23; 95% CI: 1.01-1.51) and rheumatoid arthritis (2.88; 95% CI: 2.25-3.67) compared to patients with mild psoriasis. Patients with PSA had significantly higher adjusted rates of hypertension (1.30; 95% CI: 1.01-1.68), rheumatoid arthritis (6.93; 95% CI: 5.45-8.80) and ankylosing spondylitis (6.98; 95% CI: 2.37-20.58) compared to those with severe psoriasis. CONCLUSION: Patients with mild psoriasis are less affected by comorbid conditions than those with severe psoriasis, and patients with psoriasis are less affected by comorbidities than those with PSA. Given the differences observed across severities of psoriasis and between psoriasis and PSA, each patient subgroup should be taken into consideration in clinical practice and future research.

Comparison of metabolic and prolactin variables from a six-month randomised trial of olanzapine and quetiapine in schizophrenia.

Schizophrenia patients have a potential increased risk of metabolic dysregulation during antipsychotic treatments. Our objective was to compare changes in prolactin and metabolic variables (glucose, lipids and weight) as a post-hoc analysis from a six-month, randomised, controlled study of olanzapine (OLZ, n = 171; 10-20 mg/day) or quetiapine (QUE, n = 175; 300-700 mg/day). No statistically significant treatment group differences for baseline to endpoint mean changes in body mass index (P = 0.209) or weight (P = 0.250) were observed. There was a greater incidence of clinically significant weight gain (defined as > or =7% increase from baseline) in OLZ (19.2%) compared to QUE (13.2%)-treated patients (P = 0.181). No statistically significant treatment group differences for lipids and glucose variables, either as mean change from baseline to endpoint or treatment-emergent (TE) categorical changes were found (P > or = 0.05). Incidence rates for TE diabetes were similar between treatment groups 2.5% (n = 4) in the OLZ-treatment group and 1.3% (n = 2) in the QUE-treatment group (P = 0.685). Hyperprolactinaemia was present at baseline in many patients (OLZ 32.9%; QUE 31.4%), but after 2 weeks of treatment prolactin values had reverted to normal for nearly all patients (OLZ 100%; QUE 99.4%). There were no significant treatment differences in any variable between cohorts.

Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies.

BACKGROUND: Changes in weight and metabolic parameters have been commonly reported in patients with schizophrenia. Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non-diabetic subjects. We undertook a systematic review of the efficacy and safety of metformin in reducing weight gain and metabolic abnormalities in non-diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic medication to establish if these data could potentially drive guideline development. METHODS: Medical databases were searched using terms including 'antipsychotic', 'atypical antipsychotic agent', 'antipsychotic agents', 'antipsychotic-drug' and 'metformin' and 'weight'. Studies reporting weight and/or metabolic outcomes in non-diabetic subjects with schizophrenia and bipolar disorder were included regardless of methodological type and subject age. RESULTS: Nine randomised double-blind studies and two open cohort studies evaluating metformin and changes in weight in trials up to 16 weeks were identified. In all, 495 participants received antipsychotics (mostly olanzapine), and three studies were in subjects aged < 18 years. The adult studies predominantly utilised non-Caucasian subjects with chronic schizophrenia. Weight and lifestyle intervention programmes were provided to all cohorts in eight studies, which confounded interpretation of the data. In ten studies, the addition of metformin to antipsychotic treatment was associated with either significantly attenuated weight gain or weight loss compared with control groups. Nine studies measured various glucose parameters. In four studies, subjects prescribed metformin had significantly improved glucose parameters relative to controls. The two studies of metformin in patients with first-episode schizophrenia demonstrated the largest improvement in weight and glucose parameters. CONCLUSIONS: Metformin may have some value in reducing or preventing weight gain and changes in metabolic parameters during treatment with antipsychotic medication particularly in first-episode psychosis; however, it has been predominantly studied short-term and in non-Caucasian populations. A number of new trials are due to report data 2009-2013 to aid definitive interpretation of the role of metformin. Further longer-term studies are warranted before definitive guidelines can be established.

A well-being programme in severe mental illness. Baseline findings in a UK cohort.

INTRODUCTION: Patients with severe mental illness (SMI) have higher rates of cardiovascular disease (CVD) morbidity and mortality than the general population. In the UK, data were limited regarding the known prevalence of physical health screening of SMI patients. AIMS: A total of 966 patients with SMI from seven geographically varied regions in the UK agreed to participate in a 2-year nurse-led intervention (Well-being Support Programme), designed to improve their overall physical health by providing basic physical health checks, health promotion advice, weight management and physical activity groups in secondary care. RESULTS: At baseline, only 31% of participants had undergone a recent physical health check. There were high rates of obesity (BMI > 30 in 49%), glucose abnormalities (12.4%), hypertension/prehypertension (50%), hyperlipidaemia (71%), poor diet (32%), low exercise levels (37.4%) and smoking (50%). CONCLUSIONS: Patients with SMI where healthcare professionals have concerns regarding their physical health, have potentially modifiable risk factors for CVD, which remain undiagnosed. Programmes designed to address the physical health problems in SMI need to be implemented and evaluated in this already marginalised group of people.

Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK.

OBJECTIVE: Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic. METHOD: Ninety-three patients with SMI aged 43.7 +/- 1.2 years referred themselves to this clinic. The patients were seen in weekly group sessions that involved weight measurement, discussion and education. RESULTS: Mean baseline weight was 89.5 +/- 1.8 kg [body mass index (BMI) 32.3 +/- 0.5 kg/m(2)]. Twenty-three per cent dropped out within the first 8 weeks. There was progressive statistically significant reduction in mean weight and BMI throughout the duration of monitoring with no suggestion of a plateau. The mean final weight loss was 6.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.53, P < 0.0001). CONCLUSION: Long-term weight management of obese and overweight patients with severe forms of mental illness was possible through the provision of simple lifestyle advice within the group setting.

Biomechanical analysis of Graf's dynamic spine stabilisation system ex vivo.

The most frequent causes of chronic lumbar spine instability are of degenerative or traumatic origin. Numerous anterior and posterior stabilisation devices were developed for anatomical reconstruction of the spinal alignment and fusion of the spine to restore stability. Fusion of the spine results in increased load of adjacent segments with an increased risk of secondary degeneration which might result in instability or stenosis. To avoid the disadvantages of static devices, Graf developed a method of dynamic surgical treatment of spinal column instabilities, which is based on the principle of flexible stabilisation. This study is analysing the kinematics of discoligamentary intact motion segments compared with the experimentally destabilised human lumbar spine and the influence of Graf's stabilisation. According to our results, rotational instabilities cannot be satisfactorily stabilised by Graf's ligamentoplasty. With the present ex vivo study, it could be shown that it is possible to restore stability after discoligamentary lesion and after facetectomy using Graf's dynamic lordosis ligamentoplasty.

[The stabilizing function of the glenohumeral joint capsule. Current aspects of the biomechanics of instability]. / Uber die stabilisierende Funktion der Kapsel des Glenohumeralgelenkes. Neue Aspekte zur Biomechanik der Instabilität.

The purpose of the study was to determine the influence of rotation torques on superior-inferior and anterior-posterior translation in various degrees of abduction in the glenohumeral joint. 16 cadaveric shoulders were tested using a specifically designed four-degrees-of-freedom mounting apparatus and a 6-degrees-of-freedom tracking system which allowed of dynamic and static measurements by means of ultrasound (Zebris) Internal/external rotation torques and translation forces in the inferior-superior and anterior-posterior plane were applied in 0 degrees, 45 degrees, 75 degrees and 85 degrees of abduction. Shoulders were tested intact, vented, after severing of the acromion and coracoid (7 shoulders) and after subsequent division of the anterior capsule at the glenoid margin including a T-shaped incision (8 shoulders). Venting of the capsule resulted in a significant increase in ap-translation only in abduction of less than 45 degrees. Rotation torques and an abduction of more than 45 degrees effected a centering of the humeral head against translation-forces in the anterior-posterior and superior-inferior direction. The weakening of the anterior capsule by a T-shaped incision, in which circular fibers were also severed, significantly increased the anterior translation in comparison to that obtained after an incision along the glenoid margin.(ABSTRACT TRUNCATED AT 250 WORDS)