Development of the PsAQoL: a quality of life instrument specific to psoriatic arthritis

Background: Patient reported outcome measures used in studies of psoriatic arthritis (PsA) have been found to be inadequate for determining the impact of the disease from the patient’s perspective. Objective: To produce the PsAQoL, a PsA-specific quality of life (QoL) instrument, employing the needs based model of QoL that would be relevant and acceptable to respondents, valid, and reliable. Methods: Content was derived from qualitative interviews conducted with patients with PsA. Face and content validity were assessed by field test interviews with a new sample of patients with PsA. A postal survey was conducted to improve the scaling properties of the new measure. Finally, a test-retest postal survey was used to identify the final measure and to test its scaling properties, reliability, internal consistency, and validity. Results: Analysis of the qualitative interview transcripts identified a 51 item questionnaire. Field test interviews confirmed the acceptability and relevance of the measure. Analysis of data from the first postal survey (n = 94) reduced the questionnaire to 35 items. Rasch analysis of data from the test-retest survey (n = 286) identified a 20 item version of the PsAQoL with good item fit. This version had excellent internal consistency (a = 0.91), test-retest reliability (0.89), and validity. Conclusions: The PsAQoL is a valuable tool for assessing the impact of interventions for PsA in clinical studies and trials. It is well accepted by patients, taking about three minutes to complete, is easy to administer, and has excellent scaling and psychometric properties

The Prostacyclin Analogue, Treprostinil, Used in the Treatment of Pulmonary Arterial Hypertension, is a Potent Antagonist of TREK-1 and TREK-2 Potassium Channels

Pulmonary arterial hypertension (PAH) is an aggressive vascular remodeling disease that carries a high morbidity and mortality rate. Treprostinil (Remodulin) is a stable prostacyclin analogue with potent vasodilatory and anti-proliferative activity, approved by the FDA and WHO as a treatment for PAH. A limitation of this therapy is the severe subcutaneous site pain and other forms of pain experienced by some patients, which can lead to significant non-compliance. TWIK-related potassium channels (TREK-1 and TREK-2) are highly expressed in sensory neurons, where they play a role in regulating sensory neuron excitability. Downregulation, inhibition or mutation of these channels leads to enhanced pain sensitivity. Using whole-cell patch-clamp electrophysiological recordings, we show, for the first time, that treprostinil is a potent antagonist of human TREK-1 and TREK-2 channels but not of TASK-1 channels. An increase in TASK-1 channel current was observed with prolonged incubation, consistent with its therapeutic role in PAH. To investigate treprostinil-induced inhibition of TREK, site-directed mutagenesis of a number of amino acids, identified as important for the action of other regulatory compounds, was carried out. We found that a gain of function mutation of TREK-1 (Y284A) attenuated treprostinil inhibition, while a selective activator of TREK channels, BL-1249, overcame the inhibitory effect of treprostinil. Our data suggests that subcutaneous site pain experienced during treprostinil therapy may result from inhibition of TREK channels near the injection site and that pre-activation of these channels prior to treatment has the potential to alleviate this nociceptive activity

Modulation of integrin-linked kinase (ILK) expression in human oesophageal squamous cell carcinoma cell lines by the EGF and TGFβ1 growth factors

BACKGROUND: Integrin-linked kinase (ILK) is a ubiquitously expressed protein kinase that has emerged as one of the points of convergence between integrin- and growth factor-signalling pathways. RESULTS: In this study we identify the ILK isoform expressed in five human oesophageal squamous cell carcinoma cell lines of South African origin as ILK1, and demonstrate its cellular distribution. ILK expression, although similar in the majority of the cell lines, did show variation. Furthermore, the ILK expressed was shown to be catalytically functional. The effect of growth factors on ILK expression was examined. An increase in ILK expression, following EGF and TGFβ1 exposure, was a trend across all the five oesophageal carcinoma cell lines tested. CONCLUSION: These results suggest that growth factor modulation of ILK expression relies on the internalisation/recycling of growth factor receptors and stimulation of the PI3K pathway, which may have implications with regards to cell adhesion and tumourigenesis

Gender-Based Insecurity and Opportunities for Peace: Supporting the Reintegration of Young War-Affected Mothers

In conflicts throughout the world, armed forces and groups recruit children to fight, maintain their camps, perform labor and be used for sexual purposes. The experiences of children associated with armed forces and groups (CAAFAG) are not uniform, nor can there be a uniform approach to helping them when the conflict is over. This article examines the gendered experiences of girls prior to recruitment, during their time with the fighting forces, through disarmament, demobilization and reintegration (DDR) processes, and in their communities after formal DDR has ended. We also present some of the experiences of the Participatory Action Research (PAR) Study with Young Mothers in Liberia, Sierra Leone and Northern Uganda—a study conducted predominantly with former CAAFAG which used a highly participatory methodology to help participants attain community-based reintegration. In the PAR study young mother participants took a central role in the design and implementation of their reintegration process. A mixture of self-help style psychosocial support and livelihood support were critical to their success. As this population had exceptionally low social status, lacked confidence and self-respect, and did not have rudimentary economic skills at the start, social support and community mobilization were critical in laying the groundwork for livelihood activities and facilitating the sustainability of these activities

No safety without emotional safety

This Personal View highlights how emotional safety is required for a person to keep themselves physically safe. We explain how trying to control behaviour to increase physical safety in the short term can carry the unintended consequence of reducing emotional safety, which might in turn result in higher levels of stress and hopelessness. We use examples from institutions with psychiatric inpatients to describe these processes. We argue that emotional and physical safety cannot be separated, and therefore that the absence of emotional safety compromises basic care either in an acute crisis or in the long term. Staff who fear being criticised, and so feel driven to take autonomy and responsibility away from patients, unwittingly undermine patients' experience of being empathically understood and supported, adding to patients' sense of emotional turmoil and lack of safety. We suggest that a change in culture and regulatory reform is required to bring psychiatric care more in line with the psychological needs of patients to achieve both physical and emotional safety

Characterization and regulation of wild‐type and mutant TASK‐1 two pore domain potassium channels indicated in pulmonary arterial hypertension

Key points The TASK-1 channel gene (KCNK3) has been identified as a possible disease-causing gene in heritable pulmonary arterial hypertension (PAH). In the present study, we show that novel mutated TASK-1 channels, seen in PAH patients, have a substantially reduced current compared to wild-type TASK-1 channels. These mutated TASK-1 channels are located at the plasma membrane to the same degree as wild-type TASK-1 channels. ONO-RS-082 and alkaline pH 8.4 both activate TASK-1 channels but do not recover current through mutant TASK-1 channels. We show that the guanylate cyclase activator, riociguat, a novel treatment for PAH, enhances current through TASK-1 channels but does not recover current through mutant TASK-1 channels. Pulmonary arterial hypertension (PAH) affects ∼15–50 people per million. KCNK3, the gene that encodes the two pore domain potassium channel TASK-1 (K2P3.1), has been identified as a possible disease-causing gene in heritable PAH. Recently, two new mutations have been identified in KCNK3 in PAH patients: G106R and L214R. The present study aimed to characterize the functional properties and regulation of wild-type (WT) and mutated TASK-1 channels and determine how these might contribute to PAH and its treatment. Currents through WT and mutated human TASK-1 channels transiently expressed in tsA201 cells were measured using whole-cell patch clamp electrophysiology. Localization of fluorescence-tagged channels was visualized using confocal microscopy and quantified with in-cell and on-cell westerns. G106R or L214R mutated channels were located at the plasma membrane to the same degree as WT channels; however, their current was markedly reduced compared to WT TASK-1 channels. Functional current through these mutated channels could not be restored using activators of WT TASK-1 channels (pH 8.4, ONO-RS-082). The guanylate cyclase activator, riociguat, enhanced current through WT TASK-1 channels; however, similar to the other activators investigated, riociguat did not have any effect on current through mutated TASK-1 channels. Thus, novel mutations in TASK-1 seen in PAH substantially alter the functional properties of these channels. Current through these channels could not be restored by activators of TASK-1 channels. Riociguat enhancement of current through TASK-1 channels could contribute to its therapeutic benefit in the treatment of PAH

Building Meaningful Participation in (Re)Integration Among War-Affected Young Mothers in Liberia, Sierra Leone and Northern Uganda

When young mothers, formerly associated with armed groups, return to communities, they are typically social isolated, stigmatised, and marginalised. This creates reintegration challenges for themselves, and their communities. Their children face child protection problems such as neglect, rejection and abuse. In this paper, the authors describe an innovative field practice - community based, participatory action research (PAR) - that meaningfully involved formerly associated young mothers, and other vulnerable young mothers, in their communities. The project took place in 20 field sites in three countries: Liberia, northern Uganda and Sierra Leone. It was implemented through an academic, nongovernmental organisation (NGO) partnership. The participants were 658 young mothers, both formerly associated with armed groups and other mothers seen to be vulnerable. Within the context of caring psychosocial support, these young mothers organised themselves into groups, declined their problems, and developed social actions to address and change their situations. Some project outcomes included: young mothers and their children experiencing improved social reintegration evidenced by greater family and community acceptance; more positive coping skills; and decreased participation in sex work for economic survival

Efficacy of cognitive behaviour therapy versus anxiety management for body dysmorphic disorder: a randomised controlled trial

Background: The evidence base for the effectiveness of cognitive behaviour therapy (CBT) for treating Body Dysmorphic Disorder (BDD) is weak. Aims: To determine if CBT is more effective than anxiety management (AM) in an out-patient setting. Method: A single blind, stratified parallel-group randomized controlled trial. The primary endpoint was at 12 weeks, and the Yale Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS) was the primary outcome measure. Secondary measures for BDD included the Brown Assessment of Beliefs (BABS), the Appearance Anxiety Inventory (AAI) and the Body Image Quality of Life Inventory (BIQLI). The outcome measures were collected at baseline and week 12. The CBT group, unlike the AM group, had 4 further weekly sessions that were analysed for their added value. Both groups then completed measures at their 1-month follow-up. Forty-six participants, with DSM-IV diagnosis of BDD including those with a delusional BDD were randomly allocated to either CBT or AM. Results: At 12 weeks, CBT was found to be significantly superior to AM on the BDD-YBOCS ( = -7.19, S.E. () = 2.61, p < .01, C.I. = -12.31, -2.07, d 0.99) as well as the secondary outcome measures of the BABS, AAI and BIQL. Further benefits occurred by Week 16 within the CBT group. There were no differences in outcome for those with delusional BDD or depression. Conclusions: CBT is an effective intervention for people with BDD even with delusional beliefs or depression and is more effective than anxiety management over 12 weeks