Duloxetine in the treatment of generalized anxiety disorder

Duloxetine, a medication with effects on both serotonin and noradrenaline transporter molecules, has recently been approved for the treatment of generalized anxiety disorder. The evidence for its efficacy lies in a limited number of double blind, placebo controlled comparisons. Statistically significant improvements in the Hamilton Anxiety Rating Scale from baseline were demonstrated in all studies at doses of 60 to 120 mg per day. The significance of such changes in terms of clinical improvements compared to placebo is less certain, particularly when the effect size of the change is calculated. In comparative trials with venlafaxine, duloxetine was as effective in providing relief of anxiety symptoms. In addition to improvements in clinical symptoms duloxetine has also been associated with restitution of role function as measured by disability scales. Duloxetine use is associated with nausea, dizziness, dry mouth, constipation, insomnia, somnolence, hyperhidrosis, decreased libido and vomiting. These treatment emergent side effects were generally of mild to moderate severity and were tolerated over time. Using a tapered withdrawal schedule over two weeks in the clinical trials, duloxetine was associated with only a mild withdrawal syndrome in up to about 30% of patients compared to about 17% in placebo treated patients. Duloxetine in doses of up to 200 mg twice daily did not prolong the QTc interval in healthy volunteers. Like other agents with dual neurotransmitter actions duloxetine reduces the symptoms of generalized anxiety disorder in short term treatments. Further evidence for its efficacy and safety in long term treatment is required

Continuation treatment of major depressive disorder: is there a case for duloxetine?

Duloxetine is a serotonin–noradrenaline reuptake inhibitor with established efficacy for the short-term treatment of major depressive disorder. Efficacy in continuation treatment (greater than six months of continuous treatment) has been established from both open and placebo-controlled relapse prevention and comparative studies. Seven published studies were available for review and showed that in both younger and older populations (aged more than 65 years) the acute efficacy of duloxetine was maintained for up to one year. Response to treatment was based on accepted criteria for remission of depression and in continuation studies remission rates were greater than 70%. Comparative studies showed that duloxetine was superior to placebo and comparable to paroxetine and escitalopram in relapse prevention. Importantly a study of duloxetine in patients prone to relapse of major depressive disorder showed that the medication was more effective than placebo in this difficult to treat population. Side effects of duloxetine during continuation treatment were predictable on the basis of the known pharmacology of the drug. In particular there were no significant life-threatening events which emerged with continued use of the medication. On the other hand vigilance is required since the data base on which to judge very rare events is limited by the relatively low exposure to the drug. Duloxetine has established both efficacy and safety for continuation treatment but its place as a first-line treatment of relapse prevention requires further experience. In particular further comparative studies against established agents would be useful in deciding the place of duloxetine in therapy

A comparative study of sertraline dosages, plasma concentrations, efficacy and adverse reactions in Chinese versus Caucasian patients

This prospective 6-week study examined the differences in dosage and steady state plasma concentrations of sertraline in Chinese versus Caucasian depressed patients. Two groups of Chinese patients from different geographical sites and a group of Caucasian patients were evaluated with clinical measures during an initial dose of 50 mg/day, with subsequent doses adjusted clinically. The results of 17 Australian Chinese (ACHI), 13 Malaysian Chinese (MCHI) and 15 Australian Caucasians (AC) were analysed. Despite controlling for weight, the AC subjects received a significantly higher dose than both the ACHI (P=0.002) and the MCHI groups (P=0.012). However, the mean sertraline concentration to dose ratios at weeks 1 and 6 were not significantly different between the three groups. Sertraline was effective and well tolerated in both ethnic groups with few adverse events. Although there was a lack of difference between groups in the pharmacokinetic results, Chinese depressed patients appeared to require lower dosages with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy. Further studies of the dosages, kinetics and adverse effects of selective serotonin reuptake inhibitors linked with genotyping are necessary

Exploring patient experiences and perspectives of a heart failure telerehabilitation program: a mixed methods approach

To describe patient experiences and perspectives of a group-based heart failure (HF) telerehabilitation program delivered to the homes via online video-conferencing.Limited information currently exists on patient experiences of telerehabilitation for HF. Patient feedback and end-user perspectives provide important information regarding the acceptability of this new delivery model which may have a substantial impact on future uptake.We used mixed-methods design with purposive sampling of patients with HF. We used self-report surveys and semi-structured interviews to measure patient experiences and perspectives following a 12-week telerehabilitation program. The telerehabilitation program encompassed group-based exercise and education, and were delivered in real-time via videoconferencing. Interviews were transcribed and coded, with thematic analysis undertaken.Seventeen participants with HF (mean age [SD] of 69 [12] years and 88% males) were recruited. Participants reported high visual clarity and ease of use for the monitoring equipment. Major themes included motivating and inhibiting influences related to telerehabilitation and improvement suggestions. Participants liked the health benefits, access to care and social support. Participants highlighted a need for improved audio clarity and connectivity as well computer training for those with limited computer experience. The majority of participants preferred a combined face-to-face and online delivery model.Participants in this study reported high visual clarity and ease-of-use, but provided suggestions for further improvements in group-based video telerehabilitation for HF

Timed up and go test: a reliable and valid test in patients with chronic heart failure

Background The timed up and go test (TUGT) is a short-duration functional test frequently used in rehabilitation settings as a measure of balance and mobility. Reliability and validity for patients with chronic heart failure (CHF) has yet to be determined. This prospective cohort study aimed to determine test-retest reliability of the TUGT in patients with CHF, relationships between the TUGT and other variables, including functional tests, and predictors of the TUGT. Methods and Results This was a secondary analysis of data collected in a multicenter randomized controlled trial of exercise training in recently hospitalized patients with heart failure (EJECTION-HF). The TUGT was conducted twice at baseline to determine reliability. Assessments were compared with 6-minute walk distance (6MWD), 10-m walk test time, and other clinical variables. Intraclass correlation coefficient (ICC) was used to determine test-retest reliability and correlations for relationships with other variables. A multiple regression was used to identify predictors of the TUGT. In 278 participants (mean age 62 years), the TUGT demonstrated excellent within-day test-retest reliability (ICC 0.93). A shorter (better) TUGT time was associated with longer 6MWD (r = −0.81; P < .001) and shorter 10-m walk test time (r = 0.80; P < .001). Best predictors of the TUGT were 6MWD and age, which accounted for 66% of the variance. Conclusions The TUGT appears to be a reliable and valid functional measurement in patients with CHF

Reviews

The following publications have been reviewed by the authors; Programmes of Study for Design & Technology - Reviewed by Jim PattersonManaging Design & Technology in the National Curriculum - Reviewed by David DickinsonFocus on Technology - Reviewed by Ian McLintockAccommodating Technology in Schools - Reviewed byJ.R. MathiasDesigning and Making - Reviewed by Paul SpencerTreasury of Historic Pattern and Design - Reviewed by Geoff SmithDesign & Technology in Process - Reviewed by Jonty CrockettTechnology Through Home Economics - Reviewed by Rhona HumphriesThe Soft Toy Workshop - Reviewed by Margaret Jeavons02 PAGES (Quarterly) - Reviewed by AIf MerricksAdventures in Technology - Reviewed by John EvansDesigning Starts here - Reviewed by Trevor TaylorTechnology Shaping Our World - Reviewed by Alan TruemanIntroducing Design: Technology Across the Curriculum - Reviewed by Norman CassonThe Tapestry Makers - Reviewed by Goeff SmithWoodcut with Rigby Graham - Reviewed by John Lancaste

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

The Macroecology of Sustainability

Global consumption rates of vital resources suggest that we have surpassed the capacity of the Earth to sustain current levels, much less future trajectories of growth in human population and economy

Wellbeing, mental health knowledge and caregiving experiences of siblings of people with psychosis, compared to their peers and parents: An exploratory study

Purpose The wellbeing and caregiving experiences of family carers supporting people with psychosis has garnered increasing interest. Evidence indicates that the burden of caregiving can adversely impact on parents’ wellbeing, few studies have investigated whether this is also the case for siblings, who often take on caregiving responsibilities. This exploratory study investigated the wellbeing, mental health knowledge, and appraisals of caregiving in siblings of individuals with psychosis. Method Using a cross-sectional design, 90 siblings completed three validated questionnaires: Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), Mental Health Knowledge Schedule (MAKS), and Experience of Caregiving Inventory (ECI). Data obtained were compared to general population norms and parent-carers’ scores. Multi-variable regression analyses were conducted to examine relationships between questionnaire scores and demographic characteristics including age, sex, birth order, marital status, accommodation and educational level. Results Siblings, especially sisters, had significantly poorer mental wellbeing, compared to normative scores. Conversely, they had better mental health knowledge. Siblings and parent-carers had comparable high levels of negative appraisals of caregiving experiences, but siblings reported more satisfaction with personal experiences and relationships. Education level was a significant predictor for better mental health knowledge; there were no other relationships between siblings’ demographic factors and outcomes. Conclusion Study findings suggest that siblings have overlapping as well as distinct needs, compared to parent-carers. Further research is required to better understand siblings’ experiences so as to inform development of targeted interventions that enhance wellbeing and caregiving capacity