A systematic review of the impact of patient and public involvement on service users, researchers and communities.

OBJECTIVE: Patient and public involvement (PPI) in research has expanded nationally and internationally over the last decade, and recently there has been significant attention given to understanding its impact on research. Less attention has been given to the impact of PPI on the people involved, yet it has been shown that the success of PPI in research can be reliant on the processes of engagement between these individuals and communities. This paper therefore critically explores the impact of PPI on service users, researchers and communities involved in health and social care research. DATA SOURCES: Searches were undertaken from 1995 to April 2012 in the electronic databases MEDLINE, EMBASE, PsycINFO, Cochrane library, CINAHL, HMIC and HELMIS. Searches were undertaken for grey literature using the databases InvoNet and NHS Evidence. STUDY SELECTION: Studies were included if they included the impact of PPI on individual service users, researchers or communities under research. Studies were excluded if they were in a foreign language (unless they were deemed critical to the systematic review) or were in children and adolescent services. STUDY APPRAISAL: Data were extracted using a narrative synthesis, and quality was assessed using the Critical Appraisal Skills Programme. MAIN RESULTS: Service users reported feeling empowered and valued, gaining confidence and life skills. Researchers developed a greater understanding and insight into their research area, gaining respect and a good rapport with the community. The community involved in research became more aware and knowledgeable about their condition. However, lack of preparation and training led some service users to feel unable to contribute to the research, while other service users and communities reported feeling overburdened with the work involved. Researchers reported difficulties in incorporating PPI in meaningful ways due to lack of money and time. CONCLUSION: This is the first international systematic review to focus on the impact of PPI on the people involved in the process. The beneficial and challenging impacts reported highlight the importance of optimising the context and processes of involvement, so creating the potential for PPI to impact positively on the research itself.

Mapping the impact of patient and public involvement on health and social care research: a systematic review.

BACKGROUND: There is an increasing international interest in patient and public involvement (PPI) in research, yet relatively little robust evidence exists about its impact on health and social care research. OBJECTIVE: To identify the impact of patient and public involvement on health and social care research. DESIGN: A systematic search of electronic databases and health libraries was undertaken from 1995 to 2009. Data were extracted and quality assessed utilizing the guidelines of the NHS Centre for Reviews and Dissemination 2009 and the Critical Appraisal Skills Programme (CASP). Grey literature was assessed using the Dixon-Woods et al. (2005) checklist. INCLUSION CRITERIA: All study types that reported the impact PPI had on the health and/or social care research study. MAIN RESULTS: A total of 66 studies reporting the impact of PPI on health and social care research were included. The positive impacts identified enhanced the quality and appropriateness of research. Impacts were reported for all stages of research, including the development of user-focused research objectives, development of user-relevant research questions, development of user-friendly information, questionnaires and interview schedules, more appropriate recruitment strategies for studies, consumer-focused interpretation of data and enhanced implementation and dissemination of study results. Some challenging impacts were also identified. CONCLUSION: This study provides the first international evidence of PPI impact that has emerged at all key stages of the research process. However, much of the evidence base concerning impact remains weak and needs significant enhancement in the next decade.

New insights into the molecular mechanisms underlying sensitivity/resistance to the atypical retinoid ST1926 in acute myeloid leukaemia cells: the role of histone H2A.Z, cAMP-dependent protein kinase A and the proteasome.

ST1926 is an atypical retinoid and a promising anti-tumour agent with selective apoptotic activity on the leukaemic blast. The anti-tumour activity of the compound has been associated with its capacity to induce DNA double stranded breaks. Target profiling by affinity chromatography coupled to mass spectrometry led to the identification of histone H2A.Z as a protein capable of binding ST1926 specifically. The result was confirmed by studies involving Surface Plasmon Resonance (SPR). This indicates that H2A.Z is a primary target of ST1926 and links the perturbations of the histone pathway observed by microarray analysis to the DNA damage and apoptotic responses caused by the atypical retinoid. Comparison of the whole-genome gene-expression profiles of the ST1926-sensitive NB4 and the ST1926-resistant NB4.437r cell lines demonstrated differential expression of numerous genes. Network analysis of the data indicated enrichment of the cellular pathways controlling cAMP (cyclic adenosine-monophosphate)-dependent signal transduction, proteasome-dependent protein degradation and nuclear histones in NB4.437r cells. Pharmacological inhibition of cAMP-dependent protein kinase A with H89 partially reverted resistance of NB4.437r cells to ST1926. Conversely, inhibition of the proteasome with MG132 or bortezomib blocked the apoptotic response afforded by ST1926 in the NB4 cell line. This last effect was associated with a dramatic reduction in the DNA damage caused by the atypical retinoid. The results corroborate the idea that DNA damage is an important determinant of ST1926 apoptotic activity. More importantly, they demonstrate a proactive role of the proteasome in the DNA damaging and ensuing apoptotic response observed upon the challenge of acute myeloid leukaemia cells with ST1926.

Phosphosignature predicts dasatinib response in non-small cell lung cancer.

Targeted drugs are less toxic than traditional chemotherapeutic therapies; however, the proportion of patients that benefit from these drugs is often smaller. A marker that confidently predicts patient response to a specific therapy would allow an individual therapy selection most likely to benefit the patient. Here, we used quantitative mass spectrometry to globally profile the basal phosphoproteome of a panel of non-small cell lung cancer cell lines. The effect of the kinase inhibitor dasatinib on cellular growth was tested against the same panel. From the phosphoproteome profiles, we identified 58 phosphorylation sites, which consistently differ between sensitive and resistant cell lines. Many of the corresponding proteins are involved in cell adhesion and cytoskeleton organization. We showed that a signature of only 12 phosphorylation sites is sufficient to accurately predict dasatinib sensitivity. Four of the phosphorylation sites belong to integrin ß4, a protein that mediates cell-matrix or cell-cell adhesion. The signature was validated in cross-validation and label switch experiments and in six independently profiled breast cancer cell lines. The study supports that the phosphorylation of integrin ß4, as well as eight further proteins comprising the signature, are candidate biomarkers for predicting response to dasatinib in solid tumors. Furthermore, our results show that identifying predictive phosphorylation signatures from global, quantitative phosphoproteomic data is possible and can open a new path to discovering molecular markers for response prediction.

The impact of patient and public involvement on UK NHS health care: a systematic review.

PURPOSE: Patient and public involvement (PPI) has become an integral part of health care with its emphasis on including and empowering individuals and communities in the shaping of health and social care services. The aims of this study were to identify the impact of PPI on UK National Health Service (NHS) healthcare services and to identify the economic cost. It also examined how PPI is being defined, theorized and conceptualized, and how the impact of PPI is captured or measured. DATA SOURCES: Seventeen key online databases and websites were searched, e.g. Medline and the King's Fund. STUDY SELECTION: UK studies from 1997 to 2009 which included service user involvement in NHS healthcare services. Date extraction Key themes were identified and a narrative analysis was undertaken. RESULTS OF DATA SYNTHESIS: The review indicates that PPI has a range of impacts on healthcare services. There is little evidence of any economic analysis of the costs involved. A key limitation of the PPI evidence base is the poor quality of reporting impact. Few studies define PPI, there is little theoretical underpinning or conceptualization reported, there is an absence of robust measurement of impact and descriptive evidence lacked detail. CONCLUSION: There is a need for significant development of the PPI evidence base particularly around guidance for the reporting of user activity and impact. The evidence base needs to be significantly strengthened to ensure the full impact of involving service users in NHS healthcare services is fully understood.