Activity of chitosan and its derivatives against Leishmania major and L. mexicana in vitro

There is an urgent need for safe, efficacious, affordable and field-adapted drugs for the treatment of cutaneous leishmaniasis which affects around 1.5 million new people worldwide annually. Chitosan, a biodegradable cationic polysaccharide, has previously been reported to have antimicrobial, anti-leishmanial and immunostimulatory activities. We investigated the in vitro activity of chitosan and several of its derivatives and showed that pH of the culture medium plays a critical role on anti-leishmanial activity of chitosan against both extracellular promastigotes and intracellular amastigotes of Leishmania major and Leishmania mexicana Chitosan and its derivatives were approximately 7-20 times more active at pH 6.5 than at pH 7.5 with high molecular weight chitosan being the most potent. High molecular weight chitosan stimulated the production of nitric oxide and reactive oxygen species by uninfected and Leishmania infected macrophages in a time and dose dependent manner at pH 6.5. Despite the in vitro activation of bone marrow macrophages by chitosan to produce nitric oxide and reactive oxygen species, we showed that the anti-leishmanial activity of chitosan was not mediated by these metabolites. Finally, we showed that rhodamine-labelled chitosan is taken up by pinocytosis and accumulates in the parasitophorous vacuole of Leishmania infected macrophages

Assessment of dizziness among older patients at a family practice clinic: a chart audit study

BACKGROUND: Dizziness is a common complaint among the elderly with a prevalence of over 30% in people over the age of 65. Although it is a common problem the assessment and management of dizziness in the elderly is challenging for family physicians. There is little published research which assesses the quality of dizziness assessment and management by family physicians. METHODS: We conducted a retrospective, chart audit study of patients with dizziness attending the Sunnybrook Family Practice Center of Sunnybrook and Women's College Health Sciences Center (SWCHSC) in Toronto. We audited a random sample of 50 charts of patients from 310 eligible charts. Quality indicators across all dizziness subtypes were assessed. These quality indicators included: onset and course of symptoms; symptoms in patients' own words; number of medications used; postural blood pressure changes; symptoms of depression or anxiety; falls; syncope; diagnosis; outcome; specialty referrals. Quality indicators specific to each dizziness subtype were also audited. RESULTS: 310 charts satisfied inclusion criteria with 20 charts excluded and 50 charts were randomly generated. Documentation of key quality indicators in the management of dizziness was sub-optimal. Charts documenting patients' dizziness symptoms in their own words were more likely to have a clinical diagnosis compared to charts without (P = 0.002). CONCLUSIONS: Documentation of selected key quality indicators could be improved, especially that of patients' symptoms in their own words

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes

Regularity of center-of-pressure trajectories depends on the amount of attention invested in postural control

The influence of attention on the dynamical structure of postural sway was examined in 30 healthy young adults by manipulating the focus of attention. In line with the proposed direct relation between the amount of attention invested in postural control and regularity of center-of-pressure (COP) time series, we hypothesized that: (1) increasing cognitive involvement in postural control (i.e., creating an internal focus by increasing task difficulty through visual deprivation) increases COP regularity, and (2) withdrawing attention from postural control (i.e., creating an external focus by performing a cognitive dual task) decreases COP regularity. We quantified COP dynamics in terms of sample entropy (regularity), standard deviation (variability), sway-path length of the normalized posturogram (curviness), largest Lyapunov exponent (local stability), correlation dimension (dimensionality) and scaling exponent (scaling behavior). Consistent with hypothesis 1, standing with eyes closed significantly increased COP regularity. Furthermore, variability increased and local stability decreased, implying ineffective postural control. Conversely, and in line with hypothesis 2, performing a cognitive dual task while standing with eyes closed led to greater irregularity and smaller variability, suggesting an increase in the “efficiency, or “automaticity” of postural control”. In conclusion, these findings not only indicate that regularity of COP trajectories is positively related to the amount of attention invested in postural control, but also substantiate that in certain situations an increased internal focus may in fact be detrimental to postural control

Manual therapy with and without vestibular rehabilitation for cervicogenic dizziness: a systematic review

<p>Abstract</p> <p>Background</p> <p>Manual therapy is an intervention commonly advocated in the management of dizziness of a suspected cervical origin. Vestibular rehabilitation exercises have been shown to be effective in the treatment of unilateral peripheral vestibular disorders, and have also been suggested in the literature as an adjunct in the treatment of cervicogenic dizziness. The purpose of this systematic review is to evaluate the evidence for manual therapy, in conjunction with or without vestibular rehabilitation, in the management of cervicogenic dizziness.</p> <p>Methods</p> <p>A comprehensive search was conducted in the databases Scopus, Mantis, CINHAL and the Cochrane Library for terms related to manual therapy, vestibular rehabilitation and cervicogenic dizziness. Included studies were assessed using the Maastricht-Amsterdam criteria.</p> <p>Results</p> <p>A total of fifteen articles reporting findings from thirteen unique investigations, including five randomised controlled trials and eight prospective, non-controlled cohort studies were included in this review. The methodological quality of the included studies was generally poor to moderate. All but one study reported improvement in dizziness following either unimodal or multimodal manual therapy interventions. Some studies reported improvements in postural stability, joint positioning, range of motion, muscle tenderness, neck pain and vertebrobasilar artery blood flow velocity.</p> <p>Discussion</p> <p>Although it has been argued that manual therapy combined with vestibular rehabilitation may be superior in the treatment of cervicogenic dizziness, there are currently no observational and experimental studies demonstrating such effects. A rationale for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is presented.</p> <p>Conclusion</p> <p>There is moderate evidence to support the use of manual therapy, in particular spinal mobilisation and manipulation, for cervicogenic dizziness. The evidence for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is lacking. Further research to elucidate potential synergistic effects of manual therapy and vestibular rehabilitation is strongly recommended.</p

HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab – however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody–liposomal doxorubicin conjugate that specifically targets HER2­overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. METHODS/DESIGN: HERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab. DISCUSSION: The HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02213744. Registration date: 06AUG2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2385-z) contains supplementary material, which is available to authorized users

The development of a self-help intervention to build social confidence in people living with visible skin conditions or scars: a think aloud-study

Introduction: People with a visible difference, such as scarring or a skin condition, can experience anxiety and intrusive reactions from others when in social situations. The use of products to conceal marks on the skin is provided in a number of different hospital services and by charities. However, there are relatively few psychosocial interventions available for these individuals. Objectives: To examine the views of skin camouflage users and practitioners on the acceptability, usability and need for a specifically developed cognitive behavioural therapy (CBT) self-help booklet. Methods: A think-aloud protocol and descriptive form of thematic analysis were used to ascertain participants’ views of this novel psychosocial intervention. Nine participants took part in think-aloud interviews that were analysed using thematic analysis. Six skin camouflage users and three skin camouflage practitioners participated in the study. Results: Support for the relevance, acceptability and usability of the booklet was found from both participants who used camouflage and those who provided it. However, some participants reported that they would envisage that some people would need additional support so as to be able to use the techniques described within the booklet. Conclusions: This study represents an important step towards developing a brief self-help intervention for people with living with visible skin conditions or scars and demonstrates the importance of seeking feedback from experts by experience on theoretically informed psychological interventions for this patient group