Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice

Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p < 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p < 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p < 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.     

Medicines and disease information needs of older Arabic‐speaking Australians

Aim: To explore access, satisfaction, awareness and needs for medicines and disease information (MADI) sources for older Arabic‐speaking Australians. Method: Five focus groups were conducted (in Arabic) with 29 participants with a chronic disease, aged over 65 years, and unable to speak or read English fluently. Discussions were audiotape recorded, simultaneously interpreted into English, transcribed verbatim and content analysed. Results: Arabic‐speaking general practitioners were identified as the main source of MADI, despite dissatisfaction with their counselling. Written Arabic MADI was not accessed by participants, who revealed low English and Arabic literacy levels and a reliance on family members to act as interpreters. Male participants were more concerned and active about their health and medicine information than female participants. Conclusions: This study highlighted limited availability and access to Arabic MADI for older Arabic‐speaking Australians, with reliance on Arabic‐speaking health‐care professionals for information and family members as interpreters. An accessible and sustainable system for MADI is required.     

Real-Time Monitoring of High-Intensity Focused Ultrasound Thermal Therapy Using the Manifold Learning Method

High-intensity focused ultrasound (HIFU) induces thermal lesions by increasing the tissue temperature in a tight focal region. The main ultrasound imaging techniques currently used to monitor HIFU treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation and elastography-based methods. The present study was carried out on ex vivo animal tissue samples, in which backscattered radiofrequency (RF) signals were acquired in real time at time instances before, during and after HIFU treatment. The manifold learning algorithm, a non-linear dimensionality reduction method, was applied to RF signals which construct B-mode images to detect the HIFU-induced changes among the image frames obtained during HIFU treatment. In this approach, the embedded non-linear information in the region of interest of sequential images is represented in a 2-D manifold with the Isomap algorithm, and each image is depicted as a point on the reconstructed manifold. Four distinct regions are chosen in the manifold corresponding to the four phases of HIFU treatment (before HIFU treatment, during HIFU treatment, immediately after HIFU treatment and 10-min after HIFU treatment). It was found that disorganization of the points is achieved by increasing the acoustic power, and if the thermal lesion has been formed, the regions of points related to pre- and post-HIFU significantly differ. Moreover, the manifold embedding was repeated on 2-D moving windows in RF data envelopes related to pre- and post-HIFU exposure data frames. It was concluded that if mean values of the points related to pre- and post-exposure frames in the reconstructed manifold are estimated, and if the Euclidean distance between these two mean values is calculated and the sliding window is moved and this procedure is repeated for the whole image, a new image based on the Euclidean distance can be formed in which the HIFU thermal lesion is detectable.     

What can independent research for mesothelioma achieve to treat this orphan disease?

Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival.

Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy.

Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment     

Optimizing Glioblastoma Temozolomide Chemotherapy Employing Lentiviral-based Anti-MGMT shRNA Technology

Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor''s overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM.     

Significant Association of rs77493513 Polymorphism in 3'-UTR of the NRG1 Gene with the Risk of Multiple Sclerosis Disease

Metabolic Brain Disease - Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease characterized by demyelination of the central nervous system (CNS). Neuregulin 1 (NRG1) is a...     

Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU Who Were Screened in a National Program

Background:

Hyperphenylalaninemia (HPA) and Phenylkeonuria (PKU) are metabolic errors caused by deficiency of phenylalanine hydroxylase enzyme, which results in increased level of phenylalanine. This increase is toxic to the growing brain.

Objectives:

The purpose of this study was to compare the intellectual and developmental status in HPA and PKU children with normal population in national screening program.

Patients and Methods:

In a historical cohort study, 41 PKU patients who had the inclusion criteria and 41 healthy children were evaluated. Wechsler preschool and primary scale of intelligence-3rd edition (WPPI-3) was used in order to assess the intellectual status of children 4 years and older and Ages and stages questionnaire (ASQ) was used to assess the developmental status of children 5 years and younger.

Results:

In intellectual test comparison, the two groups showed significant difference in Wechsler’s performance intelligence score and some performance subscales (P-value < 0.01). In comparison of developmental status, no significant difference was observed between the two groups (P-value > 0.05).

Conclusions:

Even with early diagnosis and treatment of PKU patients, these children show some deficiencies intellectually compared to normal children. This study emphasizes on necessity for screening intellectual and developmental status of PKU patients so that effective medical or educational measures can taken in case of deficiencies.     

Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies

Immune thrombocytopenia is a common complication of therapy with a large number of drugs. The most widely studied drug-induced immune thrombocytopenia (DIT) is caused by quinine. In most cases of DIT, antibodies bind to the platelet membrane glycoprotein (GP) Ib-IX complex in a drug-dependent fashion and bring about increased platelet clearance by the reticuloendothelial system resulting in thrombocytopenia. Here, we report the characterization of the quinine-dependent antibody activity of sera from 13 patients with quinine-induced thrombocytopenia. In our series of patients, GPIX was the most prevalent target of quinine-dependent antibodies. To identify the structural determinants of GPIX recognized by quinine-dependent antibodies, 4 chimeric mouse/human GPIX constructs and stable Chinese hamster ovary (CHO) cell lines that expressed the chimeras in association with GPIbalpha and GPIbbeta were produced. The analysis of 6 patient sera with the chimeric cell lines provided evidence for localization of the anti-GPIX quinine-dependent antibody binding site to the C-ext region (amino acid [aa] 64-135) of human GPIX. Further characterization of the C-ext region of the GPIX indicated that replacement of the Arg110 and Gln115 of the human GPIX with the corresponding residues from mouse (Gln and Glu, respectively) resulted in a significant reduction in the binding of GPIX antibodies in our series of patients, with Arg110Gln, giving a more pronounced effect than Gln115Glu. Hence, these 2 residues, particularly Arg110, play an important role in the structure of the antigenic site on GPIX recognized by anti-GPIX antibodies.