Wider institutional research cultures and their influence on patient and public involvement and engagement in health research - An institutional ethnography.

Focus on patient and public involvement and engagement (PPIE) is increasing in health policy and research governance. PPIE is considered by some to be a democratic right, and by others to be a way to improve health care and research outcomes and implementation. Most recently, policy makers, funders and (clinical) research institutions are making PPIE a strategic requirement for health research urging researchers to invite patients and relatives into their research activities. Our study is based in a Danish university hospital where PPIE has been introduced as one of five strategic research goals. We investigated how researchers experienced this new practice and how their research practices connect to the wider context of the Danish health care system. Ten cases were studied during a year using observations, interviews, and document analysis. As our method of inquiry, we used institutional ethnography to look at researchers' work from their perspective and to understand how PPIE practices are part of a larger institutional research culture reaching far beyond the individual. We found that current research culture has implications for the selection of patients and relatives and for what they are asked to do. Researchers who experienced that PPIE outcomes aided their existing research practices felt motivated. Researchers who engaged patients and relatives before it was a strategy, were ideologically driven and their approaches resulted in an increased diversity of inclusion and researcher assimilation. These findings add to the current knowledge on PPIE practices and help us understand that further development towards collaborative research practices require a change in key performance indicators and training and perhaps call for attention to our shared acceptance of knowledge generation in research.

Roles, outcomes, and enablers within research partnerships: A rapid review of the literature on patient and public involvement and engagement in health research.

BACKGROUND: Recent studies mention a need to investigate partnership roles and dynamics within patient and public involvement and engagement (PPIE) in health research, and how impact and outcomes are achieved. Many labels exist to describe involvement processes, but it is unknown whether the label has implications on partnerships and outcomes. This rapid review investigates how roles between patients, relatives and researchers in a broad variety of PPIE activities in health research are described in peer reviewed papers and explores what enables these partnerships. METHODS: Rapid review of articles published between 2012 and February 2022 describing, evaluating, or reflecting on experiences of PPIE in health research. All research disciplines and research areas were eligible. Four databases (Medline, Embase, PsychInfo and CINAHL) were searched between November 2021 and February 2022. We followed PRISMA guidelines and extracted descriptive factors: year, origin, research area and discipline, study focus, framework used and co-authorship. On a selection of articles, we performed a narrative analysis of partnership roles using Smits et al.'s. Involvement Matrix. Lastly, we performed a meta synthesis of reported enablers and outcomes of the partnerships. Patients and Relatives (PRs) have been involved in the whole rapid review process and are co-authors of this article. RESULTS: Seventy articles from various research disciplines and areas were included. Forty articles were selected for a narrative analysis of the role description of PRs and researchers, and a meta synthesis of enablers and outcomes. Most articles described researchers as decision-makers throughout the research cycle. PRs most often were partners when they were included as co-authors; they were mostly partners in the design, analysis, write-up, and dissemination stages. Enablers of partnerships included: PR training, personality of PRs and communication skills, trust, remuneration and time. CONCLUSIONS: Researchers' decision-making roles gives them control of where and when to include PRs in their projects. Co-authorship is a way of acknowledging patients' contributions which may lead to legitimation of their knowledge and the partnership. Authors describe common enablers, which can help future partnership formation.

This article investigates how other articles describe the roles patients, relatives and researchers have in patient and public involvement activities in health research. It also investigates which factors are supportive of creating these research partnerships. We searched four health research databases and found 70 relevant articles which somehow evaluated patient involvement activities in research. From these 70 articles we chose 40 which we closely investigated for descriptions of roles in the partnerships between researchers and patients and relatives. For this, we used a tool called the Involvement Matrix which uses five different roles: Listener (who is given information), Co-thinker (who is asked to give opinion), Advisor (who gives (un)solicited advice), Partner (who works as an equal partner) and Decision-maker (Who takes initiative and (final) decisions). We found that it is often researchers who take on the role of Decision-maker and that involvement often happens on their terms. We noticed that patients and relatives most often had the role of partner, when they were listed as co-authors of the article. This shows co-authorship as an authorization of their work during patient and public involvement activities. We found that patient and relative training, patients' and relatives' personality and communication skills, trust, financial reimbursement, and time were mentioned most often as enablers of good research partnerships.

Mothers' Views on the Storage and Usage of Their Children's Biological Material Under the Danish Biobanking Model: A Narrative Approach Using Epistemic Injustice.

OBJECTIVES: To investigate the knowledge and attitudes of mothers living in Denmark on the storage and usage of their children's biological material. The Danish Neonatal Screening Biobank contains blood from the Phenylketonuria-screening test. Legal, ethical, and moral concerns have been raised in several countries of how consent is obtained best in pediatric biobank governance. Research on knowledge and attitudes of Danish parents on the usage of their children's biological material is scarce. METHODS: A coproduced study between a mother and 2 researchers. We analyzed 5 online focus group interviews using Ricoeur's hermeneutical narrative analysis. RESULTS: Mothers have very little knowledge on the storage and usage of their children's biological material. They consider the Phenylketonuria-screening test to be part of a birth package, which leaves very little option of choice. They accept donating the material as a token of appreciation in an act of altruism toward the wider society but are only comfortable supporting Danish research. CONCLUSIONS: An exploration of the communal narrative build in the interviews reveal an overall feeling of duty to help benefit society, an overwhelming trust toward the health system, and epistemic unjust storage information practices.

Patient and public involvement and engagement (PPIE) in healthcare education and thesis work: the first step towards PPIE knowledgeable healthcare professionals.

In this Communication article, we share experiences of collaborating with members of the public during health education. We aim to inspire bachelor, masters and PhD students to engage with patients and the public during their undergraduate, graduate and postgraduate thesis work and to inspire educators to collaborate with patient and public involvement/engagement to develop and deliver teaching and offer their students opportunities to engage with patients and the public. We argue that when patients and the public are included in educational projects, such engagement will be an easier task once students graduate. We argue that including patients and the public in educational project work and encouraging reflections with a person with lived experience benefits students in terms of understanding the importance of reflection and validation, setting positive precedence for their future careers.

Enhanced recovery of spermatozoa and comprehensive lysis of epithelial cells from sexual assault samples having a low cell counts or aged up to one year.

Differential extraction (DE) is the most common method for processing sexual assault samples, allowing for the simultaneous recovery of sperm and epithelial cells from the swab with the separation of sperm cells from epithelial cell DNA by exploiting the differences in the cell membrane susceptibility to detergents. However, sperm cell recovery when using DE is generally 40-50% [1], which can reduce the probability of obtaining a STR profile of the semen contributor, especially if the sample is aged or has a low number of sperm cells. Here, we present a novel buffer, containing SDS and ProK that, when used as an initial incubation buffer, enhances sperm cell recovery to as high as 90%, representing a 200-300% increase over conventional DE buffer. Adjusting the incubation time and temperature provided high, reproducible sperm cell yields. Sample vortexing and replacement of SDS with sodium octyl sulfate (SOS), another sulfate-based anionic detergent, did not provide any further enhancement of the sperm cell recoveries. Furthermore, the one-step buffer provided up to a 300% increase in recovery over the conventional DE buffer when used on samples aged up to one year. STR analysis of samples containing 500 or more sperm cells treated with this buffer showed comparable results (i.e., full STR profiles; 16 of 16 loci) to those obtained using a conventional DE buffer. Finally, when the sample contained only 400 sperm cells (recovered in 100µL volume, then extracted), substantially more STR loci (14 of 16) were generated using the novel buffer in comparison to the conventional DE buffer (4 of 16 loci). This work demonstrates that this buffer may be useful as an alternative for the initial sample incubation step in differential extraction, particularly for aged or samples known to have a low number of sperm cells.

From sample to PCR product in under 45 minutes: a polymeric integrated microdevice for clinical and forensic DNA analysis.

The extraction and amplification of DNA from biological samples is laborious and time-consuming, requiring numerous instruments and sample handling steps. An integrated, single-use, poly(methyl methacrylate) (PMMA) microdevice for DNA extraction and amplification would benefit clinical and forensic communities, providing a completely closed system with rapid sample-in-PCR-product-out capability. Here, we show the design and simple flow control required for enzyme-based DNA preparation and PCR from buccal swabs or liquid whole blood samples with an ~5-fold reduction in time. A swab containing cells or DNA could be loaded into a novel receptacle together with the DNA liberation reagents, heated using an infrared heating system, mixed with PCR reagents for one of three different target sets under syringe-driven flow, and thermally-cycled in less than 45 min, an ~6-fold reduction in analysis time as compared to conventional methods. The 4 : 1 PCR reagents : DNA ratio required to provide the correct final concentration of all PCR components for effective amplification was verified using image analysis of colored dyes in the PCR chamber. Novel single-actuation, 'normally-open' adhesive valves were shown to effectively seal the PCR chamber during thermal cycling, preventing air bubble expansion. The effectiveness of the device was demonstrated using three target sets: the sex-typing gene Amelogenin, co-amplification of the ß-globin and gelsolin genes, and the amplification of 15 short tandem repeat (STR) loci plus Amelogenin. The use of the integrated microdevice was expanded to the analysis of liquid blood samples which, when incubated with the DNA liberation reagents, form a brown precipitate that inhibits PCR. A simple centrifugation of the integrated microchips (on a custom centrifuge), mobilized the precipitate away from the microchannel entrance, improving amplification of the ß-globin and gelsolin gene fragments by ~6-fold. This plastic integrated microdevice represents a microfluidic platform with potential for evolution into point-of-care prototypes for application to both clinical and forensic analyses, providing a 5-fold reduction from conventional analysis time.

Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease.

RATIONALE: Much of the total disease burden and cost of chronic obstructive pulmonary disease (COPD) is associated with acute exacerbations of COPD (AECOPD). Serum amyloid A (SAA) is a novel candidate exacerbation biomarker identified by proteomic screening. OBJECTIVES: To assess SAA as a biomarker of AECOPD. METHODS: Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) and (2) longitudinally with repeated measures (baseline vs. AECOPD vs. convalescence; 78 episodes in 37 individuals). Event severity was graded (I, ambulatory; II, hospitalized; III, respiratory failure) based on consensus guidelines. MEASUREMENTS AND MAIN RESULTS: Presumptively newly acquired pathogens were associated with onset of symptomatic AECOPD. In the cross-sectional study, both SAA and C-reactive protein (CRP) were elevated at AECOPD onset compared with stable disease (SAA median, 7.7 vs. 57.6 mg/L; P < 0.01; CRP median, 4.6 vs. 12.5 mg/L; P < 0.01). Receiver operator characteristics analysis was used to generate area-under-curve values for event severity. SAA discriminated level II/III events (SAA, 0.88; 95% confidence interval, 0.80-0.94 vs. CRP, 0.80; 95% confidence interval, 0.70-0.87; P = 0.05). Combining SAA or CRP with major symptoms (Anthonisen criteria, dyspnea) did not further improve the prediction model for severe episodes. IL-6 and procalcitonin were not informative. CONCLUSIONS: SAA is a novel blood biomarker of AECOPD that is more sensitive than CRP alone or in combination with dyspnea. SAA may offer new insights into the pathogenesis of AECOPD.

Phenotyping of cytochrome P450 2E1 in vitro and in vivo.

The aim of the present study was to develop and improve methods for phenotyping of CYP2E1, an important enzyme in the biotransformation of many industrial chemicals, therapeutic drugs and endogenous substances. The possibility to measure CYP2E1 activity in lymphocytes by using p-nitrophenol as a substrate and CYP2E1 protein levels by flow cytometry were studied in vitro. Further, the conventional chlorzoxazone method for in vivo phenotyping was studied by adjusting the dose to body weight in 10 healthy volunteers. Finally, the possibility to obtain the chlorzoxazone metabolic ratio in saliva samples was investigated. No CYP2E1 protein in lymphocytes was detected by using flow cytometry. Some enzyme activity was found in the experiments with p-nitrophenol, however, it could not be verified that it was catalyzed by CYP2E1. Chlorzoxazone and 6-hydroxychlorzoxazone were not detectable in saliva samples. The present in vivo experiments, combined with our previous data (in total 356 experiments in 50 subjects) show that the metabolic ratio increases with decreasing absorbed dose, expressed as the sum of chlorzoxazone and 6-hydroxychlorzoxazone in plasma at 2 h. The increase becomes pronounced at sum concentrations below 100 microM. In conclusion, chlorzoxazone metabolism in vivo remains the only available method for CYP2E1 phenotyping. The administered dose as well as the absorption of the probe influences the chlorzoxazone ratio. We suggest that a dose of 10 mg chlorzoxazone per kg body weight is used to estimate the CYP2E1 phenotype. Further, metabolic ratios should be disregarded if the sum of plasma chlorzoxazone and 6-hydroxychlorzoxazone is below 100 microM (blood sampled after 2 h).

Airborne cat allergen reduction in classrooms that use special school clothing or ban pet ownership.

BACKGROUND: Allergens from furred animals are brought to school mainly via clothing of pet owners. Asthmatic children allergic to cat have more symptoms when attending a class with many cat owners, and some schools allocate specific resources to allergen avoidance measures. OBJECTIVE: The aim of the current study was to evaluate the effect of school clothing or pet owner-free classes compared with control classes on airborne cat allergen levels and to investigate attitudes and allergic symptoms among the children. METHODS: Allergen measurements were performed prospectively in 2 classes with school clothing, 1 class of children who were not pet owners, and 3 control classes during a 6-week period in 2 consecutive years. Portable pumps and petri dishes were used for collection of airborne cat allergen, and a roller was used for sampling on children's clothes. Cat allergen (Fel d 1) was analyzed with enzyme-linked immunoassay and immunostaining. Both years, questionnaires were administered to the children. RESULTS: We found 4-fold to 6-fold lower airborne cat allergen levels in intervention classes compared with control classes. Levels of cat allergen were 3-fold higher on clothing of cat owners than of children without cats in control classes. Pet ownership ban seemed less accepted than school clothing as an intervention measure. CONCLUSION: For the first time, it has been shown that levels of airborne cat allergen can be reduced by allergen avoidance measures at school by using school clothing or pet ownership ban, and that both measures are equally efficient. The clinical effect of these interventions remains to be evaluated.

Reduction of exposure to laboratory animal allergens in a research laboratory.

OBJECTIVES: The purpose of this study was to determine exposure levels in the laboratory during different tasks and evaluate the effectiveness of safety equipment used to reduce personal exposure. METHODS: Personal and stationary air samples were collected during different tasks in a laboratory animal facility in which several allergen reduction strategies had been implemented. Mouse urinary allergen concentrations were measured using a polyclonal sandwich enzyme-linked immunosorbent assay. Sera from the personnel (n = 29) were analysed every 6 months for the presence of specific antibodies against mouse and rat urinary allergens, and the staff answered questionnaires on work-related symptoms, exposure and use of respiratory protection. RESULTS: The highest airborne mouse allergen levels were measured during manual emptying of cages, during changing of cages on an unventilated table and during handling of male animals on an unventilated table. Automatic emptying and cleaning of cages resulted in low airborne allergen levels in the working room. Using a ventilated cage-changing wagon reduced the allergen exposure level from 77 to 17 ng/m3. The housing of animals in ventilated cabinets, with air exhausted through the cabinet, effectively prevented the release of allergens into the ambient air. The handling of animals on ventilated benches and the use of a centralized vacuum cleaner resulted in a low exposure level. Only two subjects developed specific immunoglobulin E of > 0.35 kU/l, of whom one was reduced to negative after increased use of respiratory protection. CONCLUSIONS: Effective reduction of exposure to allergens can be achieved by several strategies, which together appear to minimize sensitization to rodents.