How to involve cancer patients at the end of life as co-researchers

The importance of user involvement in the organisation and delivery of health services and the conduct of research has increased over recent decades. Involving people at the end of life in research remains an under-developed area of research activity. The Macmillan Listening Study, a UK-wide study exploring research views and priorities of people affected by cancer, adopted a participatory research approach. Patients and carers, including two participants receiving palliative care services, collaborated in all aspects of the study as coresearchers. In this paper, we discuss the experience of working with co-researchers to collect data from two hospices. We will discuss practical, ethical and methodological challenges, including specific training needs and the emotional demands of conducting the research. Recommendations are made to facilitate successful collaboration with palliative care service users in end of life research. Palliative Medicine 2006; 20: 821 Á82

Global research priorities for interpersonal violence prevention: A modified Delphi study

© 2017, World Health Organization. All rights reserved. Objective To establish global research priorities for interpersonal violence prevention using a systematic approach. Methods Research priorities were identified in a three-round process involving two surveys. In round 1, 95 global experts in violence prevention proposed research questions to be ranked in round 2. Questions were collated and organized according to the four-step public health approach to violence prevention. In round 2, 280 international experts ranked the importance of research in the four steps, and the various substeps, of the public health approach. In round 3, 131 international experts ranked the importance of detailed research questions on the public health step awarded the highest priority in round 2. Findings In round 2, “developing, implementing and evaluating interventions” was the step of the public health approach awarded the highest priority for four of the six types of violence considered (i.e. child maltreatment, intimate partner violence, armed violence and sexual violence) but not for youth violence or elder abuse. In contrast, “scaling up interventions and evaluating their cost-effectiveness” was ranked lowest for all types of violence. In round 3, research into “developing, implementing and evaluating interventions” that addressed parenting or laws to regulate the use of firearms was awarded the highest priority. The key limitations of the study were response and attrition rates among survey respondents. However, these rates were in line with similar priority-setting exercises. Conclusion These findings suggest it is premature to scale up violence prevention interventions. Developing and evaluating smaller-scale interventions should be the funding priority

Identification and assessment of intimate partner violence in nurse home visitation

Aims and objectives: To develop strategies for the identification and assessment of intimate partner violence in a nurse home visitation programme. Background: Nurse home visitation programmes have been identified as an intervention for preventing child abuse and neglect. Recently, there is an increased focus on the role these programmes have in addressing intimate partner violence. Given the unique context of the home environment, strategies for assessments are required that maintain the therapeutic alliance and minimise client attrition. Design: A qualitative case study. Methods: A total of four Nurse–Family Partnership agencies were engaged in this study. Purposeful samples of nurses (n = 32), pregnant or parenting mothers who had self-disclosed experiences of abuse (n = 26) and supervisors (n = 5) participated in this study. A total of 10 focus groups were completed with nurses: 42 interviews with clients and 10 interviews with supervisors. The principles of conventional content analysis guided data analysis. Data were categorised using the practice–problem–needs analysis model for integrating qualitative findings in the development of nursing interventions. Results: Multiple opportunities to ask about intimate partner violence are valued. The use of structured screening tools at enrolment does not promote disclosure or in-depth exploration of women\u27s experiences of abuse. Women are more likely to discuss experiences of violence when nurses initiate nonstructured discussions focused on parenting, safety or healthy relationships. Nurses require knowledge and skills to initiate indicator-based assessments when exposure to abuse is suspected as well as strategies for responding to client-initiated disclosures. Conclusion: A tailored approach to intimate partner violence assessment in home visiting is required. Relevance to clinical practice: Multiple opportunities for exploring women\u27s experiences of violence are required. A clinical pathway outlining a three-pronged approach to identification and assessment was developed

Exposing the Interplay Between Enzyme Turnover, Protein Dynamics and the Membrane Environment in Monoamine Oxidase B

There is an increasing realization that structure-based drug design may show improved success rates by understanding the ensemble of conformations and sub-states accessible to an enzyme and how the environment affects this ensemble. Human monoamine oxidase B (MAO-B) catalyzes the oxidation of amines and is inhibited for the treatment of both Parkinson’s disease and depression. Despite its clinical importance, its catalytic mechanism remains unclear and routes to drugging this target would be valuable and relevant. Evidence of a radical in either the transition state or resting state of MAO-B is present throughout the literature, and is suggested to be a flavin semiquinone, a tyrosyl radical or both. Here we see evidence of a resting state flavin semiquinone, via absorption redox studies and electron paramagnetic resonance, suggesting that the anionic semiquinone is biologically relevant. Based on enzyme kinetic studies, enzyme variants and molecular dynamics simulations we find evidence for the crucial importance of the membrane environment in mediating the activity of MAO-B and that this mediation is related to effects on the protein dynamics of MAO-B. Further, our MD simulations identify a hitherto undescribed entrance for substrate binding, membrane modulated substrate access, and indications for half-site reactivity: only one active site is accessible to binding at a time. Our study combines both experimental and computational evidence to illustrate the subtle interplay between enzyme activity, protein dynamics and the immediate membrane environment. Understanding key biomedical enzymes to this level of detail will be crucial to inform strategies (and binding sites) for rational drug design for these drug targets

Effect of Addition of an Intimate Partner Violence Intervention to a Nurse Home Visitation Program on Maternal Quality of Life: A Randomized Clinical Trial

Importance: Intimate partner violence (IPV) is a public health problem with significant adverse consequences for women and children. Past evaluations of a nurse home visitation program for pregnant women and first-time mothers experiencing social and economic disadvantage have not consistently shown reductions in IPV. Objective: To determine the effect on maternal quality of life of a nurse home visitation program augmented by an IPV intervention, compared with the nurse home visitation program alone. Design, Setting, and Participants: Cluster-based, single-blind, randomized clinical trial at 15 sites in 8 US states (May 2011-May 2015) enrolling 492 socially disadvantaged pregnant women (≥16 years) participating in a 2.5-year nurse home visitation program. Interventions: In augmented program sites (n = 229 participants across 7 sites), nurses received intensive IPV education and delivered an IPV intervention that included a clinical pathway to guide assessment and tailor care focused on safety planning, violence awareness, self-efficacy, and referral to social supports. The standard program (n = 263 participants across 8 sites) included limited questions about violence exposure and information for abused women but no standardized IPV training for nurses. Main Outcomes and Measures: The primary outcome was quality of life (WHOQOL-BREF; range, 0-400; higher score indicates better quality of life) obtained through interviews at baseline and every 6 months until 24 months after delivery. From 17 prespecified secondary outcomes, 7 secondary end points are reported, including scores on the Composite Abuse Scale, SPAN (Startle, Physiological Arousal, Anger, and Numbness), Prime-MD Patient Health Questionnaire, TWEAK (Tolerance/Worry About Drinking/Eye-Opener/Amnesia/C[K]ut Down on Drinking), Drug Abuse Severity Test, and the 12-Item Short-Form Health Survey (physical and mental health), version 2. Results: Among 492 participants enrolled (mean age, 20.4 years), 421 (86%) completed the trial. Quality of life improved from baseline to 24 months in both groups (change in WHOQOL-BREF scores from 299.5 [SD, 54.4] to 308.2 [SD, 52.6] in the augmented program group vs from 293.6 [SD, 56.4] to 316.4 [SD, 57.5] in the standard program group). Based on multilevel growth curve analysis, there was no statistically significant difference between groups (modeled score difference, -4.9 [95% CI, -16.5 to 6.7]). There were no statistically significant differences between study groups in any of the secondary participant end points. There were no adverse events recorded in either group. Conclusions and Relevance: Among pregnant women experiencing social and economic disadvantage and preparing to parent for the first time, augmentation of a nurse home visitation program with a comprehensive IPV intervention, compared with the home visitation program alone, did not significantly improve quality of life at 24 months after delivery. These findings do not support the use of this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT01372098

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved