Action research as a catalyst for change: Empowered nurses facilitating patient participation in rehabilitation

Based on action research as a practitioner‐involving approach, this article communicates the findings of a two‐year study on implementing patient participation as an empowering learning process for both patients and rehabilitation nurses. At a rehabilitation facility for patients who have sustained spinal cord injuries, eight nurses were engaged throughout the process aiming at improving patient participation. The current practice was explored to understand possibilities and obstacles to patient participation. Observations, interviews and logbooks, creative workshops and reflective meetings led to the development and testing of four new rehabilitation initiatives aimed at enhancing patient participation. This study suggests that skills of critical reflection from action research toolbox shed light on both the notion of patient participation and caring in nursing rehabilitation. By actively involving nurses in research, the knowledge development stems from practice and the solutions therefore became practice‐oriented. In addition, the personal and professional development experienced by the involved nurses points to a secondary gain in the form of an analytical and reflective approach to complex issues in relation to patient participation, rehabilitation in general and the individual nurses' sense of professional pride.     

Combining brentuximab vedotin with dexamethasone,high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study

Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [¹⁸F]fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP. Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity. (clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02280993","term_id":"NCT02280993"}}NCT02280993).     

Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles.     

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau – a retrospective cohort study

Introduction

With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau.

Methods

In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up.

Results

We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).

Conclusions

We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.     

It's LiFe! Mobile and Web-Based Monitoring and Feedback Tool Embedded in Primary Care Increases Physical Activity: A Cluster Randomized Controlled Trial

BackgroundPhysical inactivity is a major public health problem. The It’s LiFe! monitoring and feedback tool embedded in the Self-Management Support Program (SSP) is an attempt to stimulate physical activity in people with chronic obstructive pulmonary disease or type 2 diabetes treated in primary care.ObjectiveOur aim was to evaluate whether the SSP combined with the use of the monitoring and feedback tool leads to more physical activity compared to usual care and to evaluate the additional effect of using this tool on top of the SSP.MethodsThis was a three-armed cluster randomised controlled trial. Twenty four family practices were randomly assigned to one of three groups in which participants received the tool + SSP (group 1), the SSP (group 2), or care as usual (group 3). The primary outcome measure was minutes of physical activity per day. The secondary outcomes were general and exercise self-efficacy and quality of life. Outcomes were measured at baseline after the intervention (4-6 months), and 3 months thereafter.ResultsThe group that received the entire intervention (tool + SSP) showed more physical activity directly after the intervention than Group 3 (mean difference 11.73, 95% CI 6.21-17.25; P<.001), and Group 2 (mean difference 7.86, 95% CI 2.18-13.54; P=.003). Three months after the intervention, this effect was still present and significant (compared to Group 3: mean difference 10.59, 95% CI 4.94-16.25; P<.001; compared to Group 2: mean difference 9.41, 95% CI 3.70-15.11; P<.001). There was no significant difference in effect between Groups 2 and 3 on both time points. There was no interaction effect for disease type.ConclusionsThe combination of counseling with the tool proved an effective way to stimulate physical activity. Counseling without the tool was not effective. Future research about the cost-effectiveness and application under more tailored conditions and in other target groups is recommended.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01867970","term_id":"NCT01867970"}}NCT01867970, https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01867970","term_id":"NCT01867970"}}NCT01867970 (archived by WebCite at http://www.webcitation.org/6a2qR5BSr).     

Locally-Delivered T-Cell-Derived Cellular Vehicles Efficiently Track and Deliver Adenovirus Delta24-RGD to Infiltrating Glioma

Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007). Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement.     

Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events

Aims/hypothesis

A previous pooled analysis suggested that women with diabetes are at substantially increased risk of fatal CHD compared with affected men. Additional findings from several larger and more contemporary studies have since been published on the sex-specific associations between diabetes and incident CHD. We performed an updated systematic review with meta-analysis to provide the most reliable evidence of any sex difference in the effect of diabetes on subsequent risk of CHD.

Methods

PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between 1 January 1966 and 13 February 2013. Eligible studies had to have reported sex-specific RR estimates for incident CHD associated with diabetes and its associated variability that had been adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain sex-specific RRs and the RR ratio (RRR) (women:men) for incident CHD associated with diabetes.

Results

Data from 64 cohorts, including 858,507 individuals and 28,203 incident CHD events, were included. The RR for incident CHD associated with diabetes compared with no diabetes was 2.82 (95% CI 2.35, 3.38) in women and 2.16 (95% CI 1.82, 2.56) in men. The multiple-adjusted RRR for incident CHD was 44% greater in women with diabetes than in men with diabetes (RRR 1.44 [95% CI 1.27, 1.63]) with no significant heterogeneity between studies (I ²?=?20%).

Conclusions/interpretation

Women with diabetes have more than a 40% greater risk of incident CHD compared with men with diabetes. Sex disparities in pharmacotherapy are unlikely to explain much of the excess risk in women, but future studies are warranted to more clearly elucidate the mechanisms responsible for the substantial sex difference in diabetes-related risk of CHD.     

Human-like brain hemispheric dominance in birdsong learning

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.