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- Sant'Anna, A., et al.
(author)
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Nudging healthcare professionals in clinical settings: a scoping review of the literature
- 2021
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In: Bmc Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundHealthcare organisations are in constant need of improvement and change. Nudging has been proposed as a strategy to affect people's choices and has been used to affect patients' behaviour in healthcare settings. However, little is known about how nudging is being interpreted and applied to change the behaviour of healthcare professionals (HCPs). The objective of this review is to identify interventions using nudge theory to affect the behaviour of HCPs in clinical settings.MethodsA scoping review. We searched PubMed and PsycINFO for articles published from 2010 to September 2019, including terms related to "nudging" in the title or abstract. Two reviewers screened articles for inclusion based on whether the articles described an intervention to change the behaviour of HCPs. Two reviewers extracted key information and categorized included articles. Descriptive analyses were performed on the data.ResultsSearch results yielded 997 unique articles, of which 25 articles satisfied the inclusion criteria. Five additional articles were selected from the reference lists of the included articles. We identified 11 nudging strategies: accountable justification, goal setting, suggested alternatives, feedback, information transparency, peer comparison, active choice, alerts and reminders, environmental cueing/priming, defaults/pre-orders, and education. These strategies were employed to affect the following 4 target behaviours: vaccination of staff, hand hygiene, clinical procedures, prescriptions and orders. To compare approaches across so many areas, we introduced two independent dimensions to describe nudging strategies: synchronous/asynchronous, and active/passive.ConclusionThere are relatively few studies published referring to nudge theory aimed at changing HCP behaviour in clinical settings. These studies reflect a diverse set of objectives and implement nudging strategies in a variety of ways. We suggest distinguishing active from passive nudging strategies. Passive nudging strategies may achieve the desired outcome but go unnoticed by the clinician thereby not really changing a behaviour and raising ethical concerns. Our review indicates that there are successful active strategies that engage with clinicians in a more deliberate way. However, more research is needed on how different nudging strategies impact HCP behaviour in the short and long term to improve clinical decision making.
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- Strand, Joanna, et al.
(author)
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Humanization, radiolabeling and biodistribution studies of an igg1-type antibody targeting uncomplexed psa for theranostic applications
- 2021
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In: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 14:12
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Journal article (peer-reviewed)abstract
- Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.
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15. |
- Vilhelmsson Timmermand, Oskar, et al.
(author)
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A conjugation strategy to modulate antigen binding and FcRn interaction leads to improved tumor targeting and radioimmunotherapy efficacy with an antibody targeting prostate-specific antigen
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
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Journal article (peer-reviewed)abstract
- Background: The humanized monoclonal antibody (mAb) hu5A10 specifically targets and internalizes prostate cancer cells by binding to prostate specific antigen (PSA). Preclinical evaluations have shown that hu5A10 is an excellent vehicle for prostate cancer (PCa) radiotheranostics. We studied the impact of different chelates and conjugation ratios on hu5A10′ s target affinity, neonatal fc-receptor interaction on in vivo targeting efficacy, and possible enhanced therapeutic efficacy. Methods: In our experiment, humanized 5A10 (hu5A10) was conjugated with DOTA or DTPA at a molar ratio of 3:1, 6:1, and 12:1. Surface plasmon resonance (SPR) was used to study antigen and FcRn binding to the antibody conjugates. [111 In]hu5A10 radio-immunoconjugates were administered intravenously into BALB/c mice carrying subcutaneous LNCaP xenografts. Serial Single-photon emission computed tomography (SPECT) images were obtained during the first week. Tumors were harvested and radionuclide distribution was analyzed by autoradiography along with microanatomy and immunohistochemistry. Results: As seen by SPR, the binding to PSA was clearly affected by the chelate-to-antibody ratio. Similarly, FcRn (neonatal fc-receptor) interacted less with antibodies conjugated at high ratios of chelator, which was more pronounced for DOTA conjugates. The autoradiography data indicated a higher distribution of radioactivity to the rim of the tumor for lower ratios and a more homogenous distribution at higher ratios. Mice injected with ratio 3:1111 In-DOTA-hu5A10 showed no significant difference in tumor volume when compared to mice given vehicle over a time period of 3 weeks. Mice given a similar injection of ratio 6:1111 In-DOTA-hu5A10 or 6:1111 In-DTPA-hu5A10 or 12:1111 In-DTPA-hu5A10 showed significant tumor growth retardation. Conclusions: The present study demonstrated that the radiolabeling strategy could positively modify the hu5A10′ s capacity to bind PSA and complex with the FcRn-receptor, which resulted in more homogenous activity distribution in tumors and enhanced therapy efficacy.
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16. |
- Vilhelmsson Timmermand, O., et al.
(author)
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Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2
- 2016
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 6:1
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Journal article (peer-reviewed)abstract
- Background: Prostate cancer ranks as the second most lethal malignancy in the Western world. Previous targeting of prostate-specific antigen and human kallikrein-related peptidase 2, two related enzymes abundantly expressed in prostatic malignancies, with radioimmunoconjugates intended for diagnostic purposes, have proven successful in rodent prostate cancer (PCa) models. In this study, we investigated the uptake and therapeutic efficacy of 177Lu-m11B6, a human kallikrein-related peptidase 2 (hK2)-targeting radioimmunoconjugate in a pre-clinical setting. Methods: The murine 11B6 antibody, m11B6, with high affinity for hK2, was labeled with 177Lu. Therapy planning was done from a biokinetic study in LNCaP xenografts, and therapeutic activities of 177Lu-m11B6 were administered to groups of mice. Body weight and general conditions of the mice were followed over a period of 120 days. Results: The tumor uptake in LNCaP xenografts was 30 ± 8.2 % injected activity per gram 1 week post-injection. In vivo targeting was hK2-specific as verified by a 2.5-fold decrease in tumor uptake in pre-dosed xenografts or by a fourfold lower tumor accumulation in hK2-negative DU 145 xenografts. Therapy showed a dose-dependent efficacy in LNCaP xenografts treated with 177Lu-m11B6. No therapeutic effect was seen in the control groups. The median survival for the lowest given activity of 177Lu-m11B6 was 88 days compared to that of 38 days in mice given labeled non-specific IgG. For the higher administrated activities, total tumor regression was seen with minimal normal organ toxicity. Conclusions: We have proven the possibility of radioimmunotherapy targeting hK2 in subcutaneous prostate cancer xenografts. 177Lu-m11B6 exhibited high therapeutic efficacy, with low observed toxicity. Additionally, an evaluation of the concept of pre-therapy planning using a dosimetry model was included in this radioimmunotherapy study.
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17. |
- Wolf, Axel, et al.
(author)
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Using nudges to promote clinical decision making of healthcare professionals: A scoping review
- 2022
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In: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 164
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Research review (peer-reviewed)abstract
- Nudging has been discussed in the context of policy and public health, but not so much within healthcare. This scoping review aimed to assess the empirical evidence on how nudging techniques can be used to affect the behavior of healthcare professionals (HCPs) in clinical settings. A systematic database search was conducted for the period January 2010-December 2020 using the PRISMA extension for Scoping Review checklist. Two reviewers independently screened each article for inclusion. Included articles were reviewed to extract key information about each intervention, including purpose, target behavior, measured outcomes, key findings, nudging strategies, intervention objectives and their theoretical underpinnings. Two independent dimensions, building on Kahneman's System 1 and System 2, were used to describe nudging strategies according to user action and timing of their implementation. Of the included 51 articles, 40 reported statistically significant results, six were not significant and two re -ported mixed results. Thirteen different nudging strategies were identified aimed at modifying four types of HPCs' behavior: prescriptions and orders, procedure, hand hygiene, and vaccination. The most common nudging strategy employed were defaults or pre-orders, followed by alerts or reminders, and active choice. Many in-terventions did not require any deliberate action from users, here termed passive interventions, such as auto-matically changing prescriptions to their generic equivalent unless indicated by the user. Passive nudges may be successful in changing the target outcome but may go unnoticed by the user. Future work should consider the broader ethical implications of passive nudges.
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