Psychological interventions in asthma

Asthma is a multifactorial chronic respiratory disease characterised by recurrent episodes of airway obstruction. The current management of asthma focuses principally on pharmacological treatments, which have a strong evidence base underlying their use. However, in clinical practice, poor symptom control remains a common problem for patients with asthma. Living with asthma has been linked with psychological co-morbidity including anxiety, depression, panic attacks and behavioural factors such as poor adherence and suboptimal self-management. Psychological disorders have a higher-than-expected prevalence in patients with difficult-to-control asthma. As psychological considerations play an important role in the management of people with asthma, it is not surprising that many psychological therapies have been applied in the management of asthma. There are case reports which support their use as an adjunct to pharmacological therapy in selected individuals, and in some clinical trials, benefit is demonstrated, but the evidence is not consistent. When findings are quantitatively synthesised in meta-analyses, no firm conclusions are able to be drawn and no guidelines recommend psychological interventions. These inconsistencies in findings may in part be due to poor study design, the combining of results of studies using different interventions and the diversity of ways patient benefit is assessed. Despite this weak evidence base, the rationale for psychological therapies is plausible, and this therapeutic modality is appealing to both patients and their clinicians as an adjunct to conventional pharmacological treatments. What are urgently required are rigorous evaluations of psychological therapies in asthma, on a par to the quality of pharmaceutical trials. From this evidence base, we can then determine which interventions are beneficial for our patients with asthma management and more specifically which psychological therapy is best suited for each patient

Adaptive hypermedia driven serious game design and cognitive style in school settings: an exploratory study

The potential value of adaptive hypermedia and game based learning to education and training has long been recognised, numerous studies have been undertaken in both those areas investigating its potential to improve learner performance. In particular research has indicated that tailoring content to match the prior knowledge of the user has the power to increase the effectiveness of learning systems. Recent studies have begun to indicate that Adaptive Hypermedia Learning Systems (AHLS) based on cognitive styles have the power to improve learner performance. Recent examples of research exploring avenues for effectively incorporating serious games into AHLS indicated that integrating serious games into a personalized learning environment has the potential educational benefits of combining a personalized delivery with increased learner motivation. The exploratory study presented in this paper here developed an Adaptive Hypermedia Driven Serious Game (AHDSG) based around Pask’s Holist-Serialist dimension of cognitive style. A prototype AHDSG was designed and developed to teach students about Sutton Hoo and archaeological methods. Sixty-six secondary school students participated in this study. Overall the findings of this study show that there was an improvement in performance among all participants. Although the participants that used the system which adapted to their preferred cognitive style achieved a higher mean gain score, the difference was not significant

Dosimetric consequences of the shift towards computed tomography guided target definition and planning for breast conserving radiotherapy

Background: The shift from conventional two-dimensional (2D) to three-dimensional (3D)conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy. Methods: Twenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans. Results: With conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans. Conclusion: The shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy

Regulation of the Mitogen Activated Protein Kinase Kinase (MEK)-1 by NAD-Dependent Deacetylases

Sirtuins are class III deacetylases that regulate many essential processes, including cellular stress, genome stability, and metabolism. Although these NAD+-dependent deacetylases control adaptive cellular responses, identification of sirtuin-regulated signaling targets remain under-studied. Here, we demonstrate that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, and that acetylated MEK1 is under the regulatory control of the sirtuin family members SIRT1 and SIRT2. Treatment of cells with sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequent phosphorylation of the extracellular signal-regulated kinase (ERK). Generation of an acetyl-specific MEK1 antibody demonstrates that endogenous acetylated MEK1 is extensively enriched in the nucleus following epidermal growth factor (EGF) stimulation. An acetyl-mimic of MEK1 increases inappropriate growth properties, suggesting that acetylation of MEK1 has oncogenic potential

Does Prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy?:A subanalysis from the REx Randomised Controlled Trial

Background: Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). Methods: Patients scheduled for NACRT, then potentially curative surgery (August 2014–March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13–17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1–2 weeks before surgery. Results: The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI − 3.4 to 83.7) between groups in change from baseline (p = 0.07). Conclusions: Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation

Process skill rather than motor skill seems to be a predictor of costs for rehabilitation after a stroke in working age; a longitudinal study with a 1 year follow up post discharge

<p>Abstract</p> <p>Background</p> <p>In recent years a number of costs of stroke studies have been conducted based on incidence or prevalence and estimating costs at a given time. As there still is a need for a deeper understanding of factors influencing these costs the aim of this study was to calculate the direct and indirect costs in a younger (<65) sample of stroke patients and to explore factors affecting the costs.</p> <p>Methods</p> <p>Fifty-eight patients included in a study of home rehabilitation and followed for 1 year after discharge from the rehabilitation unit, were interviewed about their use of health care services, assistance, medications and assistive devices. Costs (defined as the cost for society) were calculated. A linear regression of cost and variables of functioning, ability, community integration and health-related quality of life was done.</p> <p>Results</p> <p>Inpatient care contributed substantially to the direct cost with a mean length of stay of 92 days. Rehabilitation during the first year constituted of an average of 28 days in day clinics, 38 physiotherapy sessions and 20 occupational therapy sessions. The total direct mean cost was 80 020 € and the indirect cost 35 129 €. The direct costs were influenced by the process skill (the ability to plan and perform a given task and to adapt when needed) and presence of aphasia. Indirect costs for informal care giving increased for patients with a lower health-related quality of life as well as a low score on home integration.</p> <p>Conclusion</p> <p>Costs are high in this group of young (< 65 years) stroke patients compared to other studies, partly due to the length of the stay and partly to loss of productivity.</p

Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia.</p> <p>Methods</p> <p>Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested <it>in vitro </it>for the killing of breast cancer cells and VEGF-stimulated VEC and <it>in vivo </it>for inhibiting the tumour growth of breast tumours in a mouse xenograft model.</p> <p>Results</p> <p>We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT.</p> <p>Conclusions</p> <p>We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers and leukaemia.</p

Ideal timing to transfer from an acute care hospital to an interdisciplinary inpatient rehabilitation program following a stroke: an exploratory study

BACKGROUND: Timely accessibility to organized inpatient stroke rehabilitation services may become compromised since the demand for rehabilitation services following stroke is rapidly growing with no promise of additional resources. This often leads to prolonged lengths of stays in acute care facilities for individuals surviving a stroke. It is believed that this delay spent in acute care facilities may inhibit the crucial motor recovery process taking place shortly after a stroke. It is important to document the ideal timing to initiate intensive inpatient stroke rehabilitation after the neurological event. Therefore, the objective of this study was to examine the specific influence of short, moderate and long onset-admission intervals (OAI) on rehabilitation outcomes across homogeneous subgroups of patients who were admitted to a standardized interdisciplinary inpatient stroke rehabilitation program. METHODS: A total of 418 patients discharged from the inpatient neurological rehabilitation program at the Montreal Rehabilitation Hospital Network after a first stroke (79% of all cases reviewed) were included in this retrospective study. After conducting a matching procedure across these patients based on the degree of disability, gender, and age, a total of 40 homogeneous triads (n = 120) were formed according to the three OAI subgroups: short (less than 20 days), moderate (between 20 and 40 days) or long (over 40 days; maximum of 70 days) OAI subgroups. The rehabilitation outcomes (admission and discharge Functional Independence Measure scores (FIM), absolute and relative FIM gain scores, rehabilitation length of stay, efficiency scores) were evaluated to test for differences between the three OAI subgroups. RESULTS: Analysis revealed that the three OAI subgroups were comparable for all rehabilitation outcomes studied. No statistical difference was found for admission (P = 0.305–0.972) and discharge (P = 0.083–0.367) FIM scores, absolute (P = 0.533–0.647) and relative (P = 0.496–0.812) FIM gain scores, rehabilitation length of stay (P = 0.096), and efficiency scores (P = 0.103–0.674). CONCLUSION: OAI does not seem to affect significantly inpatient stroke rehabilitation outcomes of patients referred from acute care facilities where rehabilitation services are rapidly initiated after the onset of the stroke and offered throughout their stay. However, other studies considering factors such as the type and intensity of the rehabilitation are required to support those results