Series: Public engagement with research. Part 3: Sharing power and building trust through partnering with communities in primary care research.

BACKGROUND: This article focuses on potential strategies to support primary care researchers in working in partnership with the public and healthcare professionals. Partnership working can potentially to improve the relevance and usefulness of research and ensure better research and health outcomes. DISCUSSION: We describe what we mean by partnership working and the importance of reflecting on power and building trusting relationships. To share power in partnership working, it is essential to critically reflect on the multiple dimensions of power, their manifestations, and your own power. Power can influence relationships and therefore, it is essential to build trust with partners. Next, we outline how the context of primary care research and decisions about who you work with and how to work together, are vital considerations that are imbued with power. Lastly, we suggest different ways of working in partnership to address different dimensions of power. We provide examples from primary care research across Europe regarding how to recognise, tackle, and challenge, invisible, hidden and visible power. CONCLUSION: We conclude by proposing three calls to actions to encourage researchers working in primary care to consider the multiple dimensions of power and move towards partnership working. First is to use participatory methods to improve the inclusivity of your research. Second is to include patients and the public in decisions about the design, delivery and development of research and its outcomes. Third is to address various systemic and institutional barriers which hinder partnership working.

Partnership approaches to primary care research can potentially improve the relevance, usefulness and inclusivity of research.Working in partnership involves researchers and the public sharing power in important research decisions and building trusting relationships.Recognising and addressing power differentials and building trusting relationships requires time and effort.

Series: Public engagement with research. Part 2: GPs and primary care researchers working inclusively with minoritised communities in health research to help address inequalities.

Public engagement in health research is vital for addressing health disparities and promoting inclusivity among minoritised communities who often face barriers to accessing healthcare. Minoritised communities are groups, which have been made minorities by a dominant culture, race, ethnic group and/or social class and may experience health inequalities as a result. By incorporating diverse perspectives and lived experiences of minoritised communities, this approach aims to achieve contextually relevant research outcomes that reduce health inequalities and improve overall well-being. However, underrepresentation and lack of inclusivity challenges persist, necessitating the establishment of inclusive partnerships and grassroots participatory methodologies.To foster inclusive public engagement, it is important to overcome structural and cultural barriers, address socioeconomic challenges, and build trust with minoritised communities. This can be achieved by promoting a cultural shift that values inclusivity, providing comprehensive training to researchers, and collecting rigorous data on engagement demographics for transparency and accountability. Involving minoritised communities in decision-making through participatory research approaches enhances trust and yields successful outcomes. Additionally, allocating sufficient resources, collaborating in co-production, and prioritising the diverse needs and perspectives of stakeholders contribute to fostering inclusive public engagement in research.Overall, inclusive engagement practices particularly in primary care research have the potential to reduce health inequalities and cater to the unique requirements of minoritised communities, thereby creating more impactful outcomes and promoting equitable healthcare access.

There is an important need to engage with minoritised communities in primary care researchEngaging diverse communities in research helps produce relevant research to address health inequalities.The exclusion of minoritised communities from research can be addressed by taking action towards more inclusive engagement.

Series: Public engagement with research. Part 1: The fundamentals of public engagement with research.

BACKGROUND: In the first of a four-part series, we describe the fundamentals of public engagement in primary care research. OBJECTIVES: The article's purpose is to encourage, inform and improve the researcher's awareness about public engagement in research. For a growing number of researchers, funders and patient organisations in Europe, public engagement is a moral and ethical imperative for conducting high-quality research. DISCUSSION: Starting with an explanation of the role of public engagement in research, we highlight its diversity and benefits to research, researchers and the public members involved. We summarise principles of good practice and provide valuable resources for researchers to use in their public engagement activities. Finally, we discuss some of the issues encountered when researchers collaborate with members of the public and provide practical steps to address them. Case studies of real-life situations are used to illustrate and aid understanding. CONCLUSION: We hope this article and the other papers in this series will encourage researchers to better consider the role and practice of public engagement and the potential added value to research that collaborating with the public could provide.

A Comparative Study of Urban Park Preferences in China and The Netherlands.

Urban parks play an important role in tackling several urban challenges such as air pollution, urban heat, physical inactivity, social isolation, and stress. In order to fully seize the benefits of urban parks, it is important that they are attractive for various groups of residents. While several studies have investigated residents' preferences for urban park attributes, most of them have focused on a single geographical context. This study aimed to investigate differences in park preferences, specifically between Dutch and Chinese park users. We collected data in the Netherlands and China using an online stated choice experiment with videos of virtual parks. The data were analyzed with a random parameter mixed logit model to identify differences in preferences for park attributes between Chinese and Dutch citizens, controlling for personal characteristics. Although the results showed a general preference for parks with many trees, several differences were found between the Dutch and Chinese respondents. These differences concerned vegetation (composition of trees and flowers), the presence of benches and play facilities, and could probably be explained by differences in park use, values of nature, and landscape preferences. The findings of this study can be used as design guidelines by urban planners and landscape designers to design attractive and inclusive parks for different target groups.

Reflections from the COVID-19 pandemic on inequalities and patient and public involvement and engagement (PPIE) in social care, health and public health research.

Patient and public involvement and engagement (PPIE) has evolved to become widely established practice in social care, health and public health research in the UK. The COVID-19 pandemic has caused rapid change in practice in PPIE, notably in moving from face-to-face meetings to virtual ones. This has opened a space for reflecting on established PPIE practice, but there is a risk this is conducted too narrowly, such as only weighing our preferences and the relative pros and cons with regard to in-person versus virtual meetings. The pandemic has also demonstrated the wide inequalities in society, and hence, we argue that an inequalities lens ought to guide a deeper and wider reflection on PPIE practice. We do not seek to criticize practice pre- or during the pandemic, but to encourage using the inequalities lens as a means of encouraging debate and focusing energy on a more rigorous review of PPIE practice to widen involvement in social care, health and public health research.

The Influence of Urban Park Attributes on User Preferences: Evaluation of Virtual Parks in an Online Stated-Choice Experiment.

Urban green areas, such as parks, are becoming increasingly important in densifying cities. Urban parks encourage physical and social activity, recreation and relaxation, and thus eventually promote people's well-being. The aim of the current study is to examine which urban park attributes influence the preferences of park users, in order to offer recommendations regarding how urban parks of quality can be designed. To elicit the preferences of park visitors we designed an online stated-choice experiment. Seven park attributes, in particular the number and composition of trees and the presence of benches, side paths, a playground, litter, and flowers, were manipulated in a virtual park. In an online stated-choice task, videos of these park alternatives were presented and the preferences of 697 participants were measured. It is found that especially the number of trees and the presence of flowerbeds, particularly with a diversity of flowers, influenced participants' preferences. The presence of many benches and a playground were valued as well, but to a lesser extent. The presence of litter was found to be less troublesome than expected. Alternatives with all trees placed in one cluster were disliked. Moreover, significant standard deviations were found for the presence of side paths, a playground, and the absence of litter, which indicates that preference heterogeneity for these attributes exist. In a latent class analysis, two groups were identified, namely a Nature-loving group, who mainly valued the trees and the flowers, and an Amenity-appreciating group, who valued almost all attributes. It can be concluded that natural elements and a variety of flower species are important in an urban park, while facilities are evaluated differently by different groups of people. These findings may support park designers and policymakers in decision-making. Moreover, it illustrates the usefulness of creating a virtual park in environmental preference research.

Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate.

UNLABELLED: Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. METHODS: We studied 29 Dutch patients with a pathology-proven nonfunctioning pancreatic NET treated with (177)Lu-octreotate. All patients had a borderline or unresectable pancreatic tumor (group 1) or oligometastatic disease (defined as ≤3 liver metastases) (group 2). Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: After the treatment with (177)Lu-octreotate, successful surgery was performed in 9 of 29 patients (31%). Six patients had a Whipple procedure, 2 patients had a pylorus-preserving pancreaticoduodenectomy, and 1 patient had a distal pancreatectomy and splenectomy. The median PFS was 69 mo for patients with successful surgery and 49 mo for the other patients. For comparison, the median PFS in 90 other patients with a nonfunctioning pancreatic NET with more than 3 liver metastases or other metastases was 25 mo. CONCLUSION: Neoadjuvant treatment with (177)Lu-octreotate is a valuable option for patients with initially unresectable pancreatic NETs.

Evidence in support of the role of disturbance vegetation for women's health and childcare in Western Africa.

BACKGROUND: In savannah-dominated Bénin, West Africa, and forest-dominated Gabon, Central Africa, plants are a major source of healthcare for women and children. Due to this high demand and the reliance on wild populations as sources for medicinal plants, overharvesting of African medicinal plants is a common concern. Few studies in Western Africa, however, have assessed variations in harvest patterns across different ecological zones and within local communities. METHODS: We investigated which vegetation types women accessed to harvest medicinal plants by conducting 163 questionnaires with market vendors and women from urban and rural communities. We made botanical vouchers of cited species and collected information on their vegetation type and cultivation status. RESULTS: Secondary vegetation was a crucial asset; over 80% of the 335 Beninese and 272 Gabonese plant species came from disturbance vegetation and home gardens. In Bénin, access to trade channels allowed female market vendors to use more vulnerable species than rural and urban women who harvested for personal use. In Gabon, no relationship was found between vulnerable plant use and informant type. CONCLUSIONS: This study highlights the underemphasized point that secondary vegetation is an asset for women and children's health in both savanna-dominated and forest-dominated landscapes. The use of disturbance vegetation demonstrates women's resilience in meeting healthcare needs in the limited amount of space that is available to them. Species of conservation concern included forest species and savanna trees sold at markets in Bénin, especially Xylopia aethiopica, Khaya senegalensis, and Monodora myristica, and the timber trees with medicinal values in Gabon, such as Baillonella toxisperma.

Comparison of response evaluation in patients with gastroenteropancreatic and thoracic neuroendocrine tumors after treatment with [177Lu-DOTA0,Tyr3]octreotate.

UNLABELLED: Response Evaluation Criteria In Solid Tumors (RECIST) (unidimensional), Southwest Oncology Group (SWOG) solid tumor response criteria (bidimensional), and their modified variants are commonly used in the tumor response assessment after treatment of gastroenteropancreatic and thoracic neuroendocrine tumors (NETs). In the current study, RECIST, SWOG criteria, modified RECIST (mRECIST), and modified SWOG (mSWOG) criteria were compared in patients with NETs treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). METHODS: Two-hundred sixty-eight Dutch patients with NETs who had been treated with (177)Lu-octreotate between January 2000 and April 2007 were studied. CT or MR imaging scans were analyzed using RECIST, SWOG criteria, mRECIST, and mSWOG criteria (including the tumor response class minor response [decrease of 13%-30% for mRECIST and 25%-50% for mSWOG]). The outcomes were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Eleven patients had an unknown tumor response and were excluded. The rates of objective response (OR) (complete response + partial response [+minor response for mRECIST/mSWOG]), stable disease, and progressive disease (PD) were 28%, 49%, and 24%, respectively, according to RECIST; 25%, 49%, and 26%, respectively, according to SWOG; 44%, 33%, and 24%, respectively, according to mRECIST; and 45%, 29%, and 26%, respectively, according to mSWOG. In patients who had OR, stable disease, or PD, the median PFS was 26-30, 27-34, and 8 mo, respectively, with any of the 4 response criteria. In patients who had OR, stable disease, or PD, the median OS was 55-57, 56-74, and 11-12 mo, respectively, with any of the 4 response criteria. Subanalyses for patients who had progression before treatment start were comparable. CONCLUSION: Patients with PD as treatment outcome had significantly shorter PFS and OS than patients with an OR or stable disease with all 4 scoring systems. PFS and OS were comparable for patients with tumor regression and stable disease. The addition of the response class minor response did not improve the correlation with PFS and OS. The 4 scoring systems gave comparable results in terms of PFS and OS per categorized outcome.

Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.

PURPOSE: The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). METHODS: In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. RESULTS: In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 µmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. CONCLUSION: The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.

Treatment of gastroenteropancreatic neuroendocrine tumors with peptide receptor radionuclide therapy.

The primary treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs) is surgery with curative intent or debulking of the tumor mass. In case of metastatic disease, cytoreductive options are limited. A relatively new therapeutic modality, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs, is currently available in a number of mostly European centers. Complete and partial responses obtained after treatment with [90Y-DOTA0,Tyr3]octreotide are in the same range as after treatment with [177Lu-DOTA0,Tyr3]octreotate (i.e. 10-30%). However, significant nephrotoxicity has been observed after treatment with [90Y-DOTA0,Tyr3]octreotide. Options to improve PRRT may include combinations of radioactive labeled somatostatin analogs, intra-arterial administration, and the use of radiosensitizing drugs combined with PRRT. Other therapeutic applications of PRRT may include additional therapy cycles in patients with progressive disease after benefit from initial therapy, PRRT in adjuvant or neoadjuvant setting, or PRRT combined with new targeted therapies, such as sunitinib or everolimus. Randomized clinical trials comparing PRRT with other treatment modalities, or comparing various radioactive labeled somatostatin analogs should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs.

Tumor response assessment to treatment with [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors: differential response of bone versus soft-tissue lesions.

UNLABELLED: We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). We therefore compared the response of bone lesions with that of soft-tissue lesions to treatment with (177)Lu-octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors (NETs). METHODS: Forty-two patients with well-differentiated NETs who had bone metastases that were positive on [(111)In-DTPA(0)]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5-hydroxyindoleacetic acid) before and after treatment were compared. RESULTS: Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and soft-tissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P < 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. CONCLUSION: In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with (177)Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression.

Peptide receptor radionuclide therapy (PRRT) for GEP-NETs.

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an increasing role in the treatment of patients with inoperable or metastasised gatroenteropancreatic neuroendocrine tumours (GEP-NETs). (90)Y-DOTATOC and (177)Lu-DOTATATE are the most used radiopeptides for PRRT with comparable tumour response rates (about 15-35%). The side effects of this therapy are few and mild. However, amino acids should be used for kidney protection, especially during infusion of (90)Y-DOTATOC. Options to improve PRRT may include combinations of radioactive labelled somatostatin analogues and the use of radiosensitising drugs combined with PRRT. Other therapeutic applications of PRRT may include intra-arterial administration, neo-adjuvant treatment and additional PRRT cycles in patients with progressive disease, who have benefited from initial therapy. Considering the mild side-effects, PRRT may well become the first-line therapy in patients with metastasised or inoperable GEP-NETs if more widespread use of PRRT can be accomplished.

The natural course of preneoplastic lesions in bronchial epithelium.

PURPOSE: To study the natural history of preneoplastic lesions in the bronchial mucosa of the individuals at risk. PATIENTS AND METHODS: White light and autofluorescence bronchoscopy examinations have been done in 52 individuals harboring 134 preneoplastic lesions (WHO criteria). End points were the development of carcinoma in situ (CIS) or squamous cell cancer (SCC) or the highest category of dysplasia up until March 1, 2003 for the remaining preneoplastic lesions. RESULTS: Distribution and outcome of preneoplastic lesions have been found to be unrelated to various risk factors such as smoking history, past history of cancer, or chronic obstructive pulmonary disease. Nonstepwise changes of preneoplastic lesions are seen. Regression rate has been 54%. Progression to CIS/SCC has been 13.4% (18 of 134) and was for severe dysplasia, significantly higher (P < 0.003) than preneoplastic lesions showing lower-grade dysplasia (squamous metaplasia, mild and moderate dysplasia). Time to progression was not significantly different. However, when analyzed per individual, no significant difference of progression rate between individuals with or without severe dysplasia was seen (39% versus 26%; P = 0.36). CONCLUSIONS: The 54% regression rate of all preneoplastic lesions, 26% to 39% progression rate to CIS/SCC of individuals with lower-grade dysplasia or severe dysplasia with no significant difference in progression rate and time to progression combined with nonstepwise histologic changes unrelated to the initial histologic grading indicate that one cannot differentiate the potentially more malignant preneoplastic lesions among the many preneoplastic lesions present in the bronchial mucosa. The initial WHO classification of any preneoplastic lesion cannot be reliably used for accurate risk assessment of field carcinogenesis.