708 research outputs found
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
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Psychological interventions for post-traumatic stress disorder (PTSD) in people with severe mental illness
BACKGROUND: Increasing evidence indicates that individuals who develop severe mental illness (SMI) are also vulnerable to developing post-traumatic stress disorder (PTSD), due to increased risk of exposure to traumatic events and social adversity. The effectiveness of trauma-focused psychological interventions (TFPIs) for PTSD in the general population is well-established. TFPIs involve identifying and changing unhelpful beliefs about traumatic experiences, processing of traumatic memories, and developing new ways of responding to cues associated with trauma. Little is known about the potential feasibility, acceptability and effectiveness of TFPIs for individuals who have a SMI and PTSD. OBJECTIVES: To evaluate the effectiveness of psychological interventions for PTSD symptoms or other symptoms of psychological distress arising from trauma in people with SMI. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Study-Based Register (up until March 10, 2016), screened reference lists of relevant reports and reviews, and contacted trial authors for unpublished and/or specific outcome data. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) which investigated TFPIs for people with SMI and PTSD, and reported useable data. DATA COLLECTION AND ANALYSIS: Three review authors (DS, MF, IN) independently screened the titles and abstracts of all references identified, and read short-listed full text papers. We assessed risk of bias in each case. We calculated the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes, and the mean difference (MD) and 95% CI for continuous data, on an intention-to-treat basis. We assessed quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and created 'Summary of findings' tables. MAIN RESULTS: Four trials involving a total of 300 adults with SMI and PTSD are included. These trials evaluated three active intervention therapies: trauma-focused cognitive behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing (EMDR), and brief psychoeducation for PTSD, all delivered via individual sessions. Our main outcomes of interest were PTSD symptoms, quality of life/well-being, symptoms of co-morbid psychosis, anxiety symptoms, depressive symptoms, adverse events and health economic outcomes. 1. TF-CBT versus usual care/waiting list Three trials provided data for this comparison, however, continuous outcome data available were more often found to be skewed than unskewed, leading to the necessity of conducting analyses separately for the two types of continuous data. Using the unskewed data only, results showed no significant differences between TF-CBT and usual care in reducing clinician-rated PTSD symptoms at short term (1 RCT, n =13, MD 13.15, 95% CI -4.09 to 30.39,low-quality evidence). Limited unskewed data showed equivocal results between groups in terms of general quality of life (1 RCT, n = 39, MD -0.60, 95% CI -4.47 to 3.27, low-quality evidence), symptoms of psychosis (1 RCT, n = 9, MD -6.93, 95% CI -34.17 to 20.31, low-quality evidence), and anxiety (1 RCT, n = 9, MD 12.57, 95% CI -5.54 to 30.68, very low-quality evidence), at medium term. The only available data on depression symptoms were skewed and were equivocal across groups at medium term (2 RCTs, n = 48, MD 3.26, 95% CI -3.66 to 10.18, very low-quality evidence). TF-CBT was not associated with more adverse events (1 RCT, n = 100, RR 0.44, 95% CI 0.09 to 2.31, low-quality evidence) at medium term. No data were available for health economic outcomes. Very limited data for PTSD and other symptoms were available over the long term. 2. EMDR versus waiting listOne trial provided data for this comparison. Favourable effects were found for EMDR in terms of PTSD symptom severity at medium term but data were skewed (1 RCT, n = 83, MD -12.31, 95% CI -22.72 to -1.90, very low-quality evidence). EMDR was not associated with more adverse events (1 RCT, n = 102, RR 0.21, 95% CI 0.02 to 1.85, low-quality evidence). No data were available for quality of life, symptoms of co-morbid psychosis, depression, anxiety and health economics.3. TF-CBT versus EMDROne trial compared TF-CBT with EMDR. PTSD symptom severity, based on skewed data (1 RCT, n = 88, MD -1.69, 95% CI -12.63 to 9.23, very low-quality evidence) was similar between treatment groups. No data were available for the other main outcomes.4. TF-CBT versus psychoeducationOne trial compared TF-CBT with psychoeducation. Results were equivocal for PTSD symptom severity (1 RCT, n = 52, MD 0.23, 95% CI -14.66 to 15.12, low-quality evidence) and general quality of life (1 RCT, n = 49, MD 0.11, 95% CI -0.74 to 0.95, low-quality evidence) by medium term. No data were available for the other outcomes of interest. AUTHORS' CONCLUSIONS: Very few trials have investigated TFPIs for individuals with SMI and PTSD. Results from trials of TF-CBT are limited and inconclusive regarding its effectiveness on PTSD, or on psychotic symptoms or other symptoms of psychological distress. Only one trial evaluated EMDR and provided limited preliminary evidence favouring EMDR compared to waiting list. Comparing TF-CBT head-to-head with EMDR and brief psychoeducation respectively, showed no clear effect for either therapy. Both TF-CBT and EMDR do not appear to cause more (or less) adverse effects, compared to waiting list or usual care; these findings however, are mostly based on low to very low-quality evidence. Further larger scale trials are now needed to provide high-quality evidence to confirm or refute these preliminary findings, and to establish which intervention modalities and techniques are associated with improved outcomes, especially in the long term
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
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