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Background: Mesothelioma is an aggressive thoracic tumour with a poor prognosis. The only treatment that extends survival is chemotherapy. However, in the UK, up to 50% of patients who are suitable for chemotherapy choose not to receive it, opting for active symptom control instead. The aim of this prospective, single-centre observational study was to describe the characteristics of patients who chose active symptom control over chemotherapy and explore their reasons for doing so., Methods: Two hundred consecutive patients with mesothelioma from one UK centre were included. Eligibility for chemotherapy and choice of first-line treatment were recorded prospectively. Patient characteristics and outcomes were compared using descriptive statistics, regression analysis and survival analysis. Reasons for choosing active symptom control over chemotherapy were extracted, retrospectively., Results: People who chose active symptom control were older, more likely to be female and had worse performance statuses than patients who received front-line chemotherapy. Concern over side effects, the modest survival benefit and previous adverse experiences with chemotherapy were reported as reasons for the decision. Median survival was 13.9 months in the chemotherapy group compared with 6.7 months in the active symptom control group., Conclusions: This is the first study to describe the characteristics of patients with mesothelioma who chose active symptom control over chemotherapy, in the front-line setting. Important differences were seen between this group and patients who received chemotherapy, although confounding is likely to have affected some outcomes. Future research could use qualitative methods to explore patients' reasons for choosing active symptom control, and to further elucidate the decision-making process.

Background: Older people often have multimorbidity requiring a complex regime of medications, which may change following hospital discharge, thus presenting new challenges. The experiences of older people, who manage their own medications, in particular following hospital discharge, have rarely been studied., Aim: This study investigates the experiences of older people with multimorbidity taking multiple medications after hospital discharge and how they cope with medication-taking., Method: A qualitative-descriptive approach with ten interviews was chosen. The data were coded openly into two groups according to Saldaña (2013)., Results: It is important for older people, in spite of their multimorbidity, to maintain their independence and maintain responsibility for taking their medications. Routines are developed from taking medications over many years and the new medications are easily integrated. Unclear information by the medical staff and the inability of the older people to obtain the medications after discharge may lead to mistakes or interruptions in the drug therapy at home. The key person for this group is the general practitioner, even concerning the drug therapy initiated in hospital., Conclusion: It is advisable to adapt discharge education to the needs of older people, especially with regard to their drug therapy, to its integration into their daily routine, and to any possible shortcomings in their medication management.

Aims: To explore attitudes towards medicines, polypharmacy and adherence in patients with chronic kidney disease (CKD)., Background: Polypharmacy is common in CKD and associated with medication non-adherence., Methods: As part of a mixed methodology project, a purposive sample of ten participants were recruited and interviewed to explore attitudes to medicines and reasons for adherent and non-adherent behaviour., Results: Several reasons for non-adherence were reported. Interviewees described a variety of attitudes towards medicines. Complex medicine regimes were a frequently cited contributing factor in poor adherence. Concerns about or experience of side effects had a negative impact on adherence. Prioritisation of medicines was evident and the importance of communication with health professionals was a consistent theme., Conclusions: Non-adherence with prescribed medicines in CKD is a complex phenomenon, which has implications for clinical outcomes and cost. Adherent behaviour may change over time. Further research in this field is needed. No single intervention is likely to enhance adherence for all and clinicians should consider a variety of options to improve adherence with prescribed medicines., (© 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Background: Different patient groups are known to use herbal remedies and conventional drugs concomitantly (co-use). This poses a potential risk of herb-drug interaction through altering the drug's pharmacokinetics or pharmacodynamics. Little is known about co-use among patients in general practice. The primary aim of this study was to compare patients in general practice that co-use herbal remedies and conventional drugs with those who do not. The secondary aim was to register the herb-drug combinations with potential clinical relevant interactions among the co-users., Method: A questionnaire based cross-sectional study conducted in the autumn 2011 in a general practice office with four general practitioners (GPs) and one intern in Western Norway. Adults >18 years who came for an office visit were invited. The questionnaire asked about demographics, herbal use, conventional drug use and communication about herbal use. Multivariable logistic regression was used to compare co-users to the other patients., Results: Of the 381 patients who completed the questionnaire, the prevalence of herbal use was 44%, with bilberry (41%), green tea (31%), garlic (27%), Aloe vera (26%) and echinacea (18%) as the most frequently used. Among those using conventional drugs regularly, 108 (45%) co-used herbs. Close to 40% of patients on anticoagulants co-used herbs, with garlic and bilberry as the most frequent herbs. Compared to all other patients, co-users had significantly (p < 0.05) increased odds to be female (adjOR 2.0), age above 70 years (adjOR 3.3), use herbs to treat an illness (adjOR 4.2), use two or more herbs (polyherbacy, adjOR 12.1) and having experienced adverse effects of herbal use (adjOR 37.5). Co-use was also associated with use of analgesics or dermatological drugs (adjOR 5.1 and 7.9 respectively). Three out of four patients did not discuss herbal use with any health care professional., Conclusion: A sizable proportion of the GP patients co-used herbs with conventional drugs, also combinations with reported interaction potential or additive effects like anticoagulants and garlic. The low disclosure of herbal use to their GP, polyherbacy and the risk of interactions in vulnerable groups like elderly and chronically ill patients, warrant increased awareness among GPs.

Objective: Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression., Subjects and Methods: Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean±SD=39±12) years. Patients were prescribed paroxetine (n=11) or sertraline (n=13) for 4weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4weeks., Results: Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group., Conclusion: Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment response, potentially by restoring brain bioenergetics at the cellular level., Method: Fifty-two women with major depressive disorder were enrolled in an 8-week double-blind placebo-controlled clinical trial and randomly assigned to receive escitalopram in addition to either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score., Results: In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8. There were no differences between treatment groups in the proportion of patients who discontinued treatment prematurely (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all reported adverse events (creatine: 36 events; placebo: 45 events)., Conclusions: The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder.

We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No difference in the achievement of ≥50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress processes might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression. Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study.

Background: Observations that antagonists of the N-methyl-d-aspartate (NMDA) receptor of glutamatergic neurons can mimic symptoms of schizophrenia have raised the hope that NMDA agonists can improve symptoms. On the basis of encouraging results of trials in which NMDA agonists were added to antipsychotics, we conducted an adequately powered randomized controlled trial adding d-serine, an NMDA modulator, to antipsychotics., Method: This study was a 195-patient, multicenter, double-blind, randomized, placebo-controlled, 16-week trial of d-serine 2 g/d as an add-on treatment to antipsychotics. Subjects had DSM-IV schizophrenia or schizoaffective disorder and were inpatients or outpatients stabilized on antipsychotics, with persistent negative symptoms. The primary outcome measures were changes in negative symptoms and cognition as measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery, respectively. The study was performed between 2003 and 2007., Results: Mean total Positive and Negative Syndrome Scale scores at baseline were 75.5. Subjects receiving d-serine and placebo improved in scores on the SANS and MATRICS, but no significant differences were observed between groups: improvement on SANS was 11.4% for d-serine vs 14.8% for placebo, F1,147=1.18, P=.32; and improvement on MATRICS was 6.8% for d-serine vs 6.1% for placebo, F1,125=0.96, P=.39, respectively. d-Serine was well tolerated., Discussion: This study did not find a significant difference between drug and placebo. However, the results are limited by a relatively large placebo response and somewhat lower-achieved doses than in prior studies. Future studies will administer higher doses and will attempt to affect the NMDA receptor using other mechanisms, such as agonists of the presynaptic metabotropic glutamate 2/3 receptor or glycine reuptake inhibitors., Trial Registration: ClinicalTrials.gov identifier: NCT00138775., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Objective: This 22-week, open-label study, conducted between November 2006 and September 2008 in a community setting, was designed to determine if weight gain during olanzapine treatment can be prevented or mitigated with adjunctive treatment algorithms that include amantadine, metformin, and zonisamide., Method: Outpatients with schizophrenia or schizoaffective disorder (DSM-IV-TR criteria) were randomly assigned to olanzapine alone (n = 50), olanzapine plus algorithm A (olanzapine + A [amantadine 200 mg/d with possible switches to metformin 1,000-1,500 mg/d and then to zonisamide 100-400 mg/d; n = 76]), or olanzapine plus algorithm B (olanzapine + B [metformin 1,000-1,500 mg/d with possible switches to amantadine 200 mg/d and then to zonisamide 100-400 mg/d; n = 73]). Brief weight management education was provided at baseline. The primary outcome measure was comparison of mean weight gain between olanzapine and pooled olanzapine + A and olanzapine + B results., Results: Least squares mean ± SE weight gain was 2.76 ± 0.75 kg for olanzapine, 2.40 ± 0.65 kg for olanzapine + A, and 0.65 ± 0.63 kg for olanzapine + B. Mean weight gain during olanzapine treatment did not differ significantly from pooled results for olanzapine + A and olanzapine + B (P = .065). Participants treated with olanzapine + B experienced significantly less mean weight gain than olanzapine-treated participants (P = .036)., Conclusions: Pooled treatment algorithm results were not significantly different from olanzapine monotherapy in mitigating weight gain. However, participants who received treatment with metformin with possible progression to amantadine and then zonisamide had significantly less mean weight gain than participants treated with olanzapine alone. Progression of some participants through the algorithm indicated that a single therapy solution may not be adequate for every patient. Patients treated with olanzapine should receive regular weight monitoring., Trial Registration: clinicaltrials.gov Identifier: NCT00401973., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Arts-based programs have improved HIV-related knowledge, attitudes, and behavior in general and at-risk populations. With HIV transformed into a chronic condition, this study compares patients at consecutive stages of receiving antiretroviral treatment, coinciding with exposure to a radio-and-theater-based educational program (unexposed [N = 120], just exposed [N = 77], Exposed a month ago [N = 60]). Exposure was associated with significantly higher HIV-related knowledge (15-20%, all p < .01), lower levels of stigma (2-7% lower, all p < .10), and over four times the adjusted odds of asking doctors questions about HIV (p = .07). Higher dose of exposure was associated with lower felt stigma (28% reduction per message recalled), greater odds of consistent condom use (adjusted odds ratio [AOR]: 1.12, p = .01), doctor-patient communication (AOR: 1.20, p = .003), peer advice-giving (AOR: 1.18, p = .03) and HIV-related advocacy (AOR: 2.35, p = .07). Similar partnerships between arts-based nongovernmental organizations and government hospitals may improve patient outcomes in HIV treatment settings.

Background and Objectives: Buprenorphine and methadone are widely used for the treatment of opioid dependence, but their diversion and/or misuse are frequent. In principle, buprenorphine/naloxone combination therapy should be associated with a lower frequency of drug abuse/misuse than methadone. This study assessed the efficacy of the substitution of buprenorphine treatment with the buprenorphine/naloxone combination in opioid-dependent patients., Material and Methods: 3812 drug-addicted outpatients selected from 10 Italian Public Services for Addiction (Ser.T.) centres in Naples (Italy) were enrolled: 3105 (81.5%) were treated with methadone and 707 (18.5%) with buprenorphine. The buprenorphine treatment was switched to buprenorphine/naloxone (4:1), and the patients were followed for about 1 year. The number of subjects still on treatment after 1 year, their status according to social, educational and toxicologic (assessed by a urine toxicology test) parameters were assessed., Results: 1 year after the therapy switch, the number of patients still on treatment was similarly reduced with methadone (2883; -7.5%) and buprenorphine/naloxone (632; -10.6%; p=0.369). However, in patients treated with buprenorphine/naloxone, a significant improvement was reported in social life status (63% versus 39% of the buprenorphine/naloxone and methadone treated subjects, respectively, were married/cohabiting p<0.001), in the educational level (43% of buprenorphine/naloxone treated versus 32% of the methadone treated subjects obtained at least a high school certificate, p<0.001) and in the toxicological conditions (53% of buprenorphine/naloxone treated subject versus 30% of methadone treated individuals had opioid- and cocaine- negative urine tests, p<0.001)., Discussion: These preliminary data suggest that buprenorphine/naloxone treatment of opioid dependence reduces the percentage of treated subjects similarly to methadone, and is associated with an improvement in social life, educational and toxicological conditions, compared with methadone treatment. However, we cannot exclude a selection bias, i.e. patients who were more likely to stabilize their opiate dependence switched to buprenorphine/naloxone.

In short-term efficacy studies, coprescription of a benzodiazepine improves first-month adherence and response to antidepressant treatment. We used Veterans Health Administration data to examine the impact of coprescribed benzodiazepines on initial antidepressant adherence in routine clinical practice and the risks of long-term benzodiazepine use, abuse, and dependence. Our study population was 43,915 Veterans Health Administration patients diagnosed with depression and started on an antidepressant between October 2006 and September 2007. Using logistic regression, adjusting for demographic and clinical covariates, we predicted the likelihood that patients received antidepressant treatment for an adequate duration (90 days), with our primary independent variable of interest being receipt of a benzodiazepine on the same day as the start of the antidepressant. We also assessed the frequency and characteristics of patients whose benzodiazepine use persisted for 1 year or who were diagnosed with anxiolytic abuse or dependence after receiving combined treatment. The adjusted probability of receiving antidepressant treatment of adequate duration was 42.4% for patients who received a benzodiazepine with their initial antidepressant compared with 39.3% for patients initially treated with an antidepressant alone (P < 0.001). Among patients who received combined treatment, 14.1% subsequently used benzodiazepines for at least 1 year, and 0.7% were diagnosed with anxiolytic abuse or dependence. Anxiolytic abuse or dependence, but not long-term benzodiazepine use, was associated with other substance use disorders. These findings should be considered by clinicians when assessing the individual risks and benefits of combining a benzodiazepine with antidepressant treatment.

Background: In this chart review, we attempted to evaluate the benefits of adding aripiprazole in veterans with military-related PTSD and comorbid depression, who had been minimally or partially responsive to their existing medications., Methods: A retrospective chart review of patients who received an open-label, flexible-dose, 12- week course of adjunctive aripiprazole was conducted in 27 military veterans meeting DSM-IV criteria for PTSD and comorbid major depression. Concomitant psychiatric medications continued unchanged, except for other antipsychotics which were discontinued prior to initiating aripiprazole. The primary outcome variable was a change from baseline in the PTSD checklist-military version (PCL-M) and the Beck Depression Inventory (BDI-II)., Results: PTSD severity (Total PCL scores) decreased from 56.11 at baseline to 46.85 at 12-weeks (p < 0.0001 from Wilcoxon signed rank test) and the depression severity decreased from 30.44 at baseline to 20.67 at 12-weeks (p < 0.0001 from Wilcoxon signed rank test). Thirty seven percent (10/27) were considered responders, as defined by a decrease in total PCL scores of at least 20 percent and 19% (5/27) were considered as responders as defined by a decrease in total BDI score of at least 50%., Conclusions: The addition of aripiprazole contributed to a reduction in both PTSD and depression symptomatology in a population that has traditionally demonstrated poor pharmacological response. Further investigations, including double-blind, placebo-controlled studies, are essential to confirm and further demonstrate the benefit of aripiprazole augmentation in the treatment of military related PTSD.

The medication-taking behaviour of patients may be key to avoiding the serious long-term micro- and macrovascular complications of Type 2 diabetes. However, the polypharmacy often required to achieve good metabolic control can be a significant barrier to adequate adherence. Reducing treatment complexity can be achieved through the use of single-tablet fixed-dose combinations of two oral hypoglycaemic agents. Studies to date suggest that this approach can significantly improve adherence over separate tablet dual therapy and has the potential to improve metabolic and clinical outcomes. A range of fixed-dose combination oral hypoglycaemic agents in several different dosage strengths are available and the strategies for optimal implementation of these options continue to evolve. This article describes the extent and consequences of poor adherence to oral hypoglycaemic agents in Type 2 diabetes and discusses the potential contribution of fixed-dose combinations to the provision of improved care.