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Intracellular pathogens secrete effectors to manipulate their host cells. Histoplasma capsulatum (Hc) is a fungal intracellular pathogen of humans that grows in a yeast form in the host. Hc yeasts are phagocytosed by macrophages, where fungal intracellular replication precedes macrophage lysis. The most abundant virulence factor secreted by Hc yeast cells is Calcium Binding Protein 1 (Cbp1), which is absolutely required for macrophage lysis. Here we take an evolutionary, structural, and cell biological approach to understand Cbp1 function. We find that Cbp1 is present only in the genomes of closely related dimorphic fungal species of the Ajellomycetaceae family that lead primarily intracellular lifestyles in their mammalian hosts (Histoplasma, Paracoccidioides, and Emergomyces), but not conserved in the extracellular fungal pathogen Blastomyces dermatitidis. We observe a high rate of fixation of non-synonymous substitutions in the Cbp1 coding sequences, indicating that Cbp1 is under positive selection. We determine the de novo structures of Hc H88 Cbp1 and the Paracoccidioides americana (Pb03) Cbp1, revealing a novel "binocular" fold consisting of a helical dimer arrangement wherein two helices from each monomer contribute to a four-helix bundle. In contrast to Pb03 Cbp1, we show that Emergomyces Cbp1 orthologs are unable to stimulate macrophage lysis when expressed in the Hc cbp1 mutant. Consistent with this result, we find that wild-type Emergomyces africanus yeast are able to grow within primary macrophages but are incapable of lysing them. Finally, we use subcellular fractionation of infected macrophages and indirect immunofluorescence to show that Cbp1 localizes to the macrophage cytosol during Hc infection, making this the first instance of a phagosomal human fungal pathogen directing an effector into the cytosol of the host cell. We additionally show that Cbp1 forms a complex with Yps-3, another known Hc virulence factor that accesses the cytosol. Taken together, these data imply that Cbp1 is a fungal virulence factor under positive selection that localizes to the cytosol to trigger host cell lysis.

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.

In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2) responses and the production of interleukin (IL)-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα). While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC) IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11c(cre)IL-4Rα(-/lox)) BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11c(cre)IL-4Rα(-/lox) mice. Following infection with L. major, CD11c(cre)IL-4Rα(-/lox) mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11c(cre)IL-4Rα(-/lox) mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11c(cre)IL-4Rα(-/lox) mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected DCs due to reduced killing effector functions.

IL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(cre)Il4ra(-/lox)) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Ralpha expression (iLck(cre)Il4ra(-/lox)). In the study presented here we further investigated their role in liver granulomatous inflammation. Frequencies and numbers of macrophage, lymphocyte or granulocyte populations, as well as Th1/Th2 cytokine responses were similar in Schistosoma mansoni-infected LysM(cre)Il4ra(-/lox) liver granulomas, when compared to Il4ra(-/lox) control mice. In contrast, a shift to Th1 responses with high IFN-gamma and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLck(cre)Il4ra(-/lox) and Il4ra(-/-) mice. As expected, alternative macrophage activation was reduced in both LysM(cre)Il4ra(-/lox) and iLck(cre)Il4ra(-/lox) granulomas with low arginase 1 and heightened nitric oxide synthase RNA expression in granuloma macrophages of both mouse strains. Interestingly, a discrete subpopulation of SSC(high)CD11b+I-A/I-E(high)CD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysM(cre)Il4ra(-/lox) but not in iLck(cre)Il4ra(-/lox) granulomas. While aaMphi were in close proximity to the parasite eggs in Il4ra(-/lox) control mice, MMR+Ym1+ macrophages in LysM(cre)Il4ra(-/lox) mice were restricted to the periphery of the granuloma, indicating that they might have different functions. In vivo IL-10 neutralisation resulted in the disappearance of MMR+Ym1+ macrophages in LysM(cre)Il4ra(-/lox) mice. Together, these results show that IL-4Ralpha-responsive T cells are essential to drive alternative macrophage activation and to control granulomatous inflammation in the liver. The data further suggest that in the absence of macrophage-specific IL-4Ralpha signalling, IL-10 is able to drive mannose receptor- and Ym1-positive macrophages, associated with control of hepatic granulomatous inflammation.

Background: Patient online access to medical records is assumed to foster patient empowerment and advance patient-centred healthcare. Since July 2020, patients in the Netherlands have been legally entitled to electronically access their medical record in general practice. Experience from pioneering countries has shown that despite high patient interest, user rates often remain low. How to best support implementation depends on individual needs and expectations of patient populations, which are as yet unknown in the Dutch context., Objective: To understand Dutch patients' needs and expectations with regard to online access to their medical record in general practice., Method: Twenty participants completed semi-structured individual interviews via video or telephone call. Transcripts of interviews underwent template analysis combining deductive and inductive coding using Atlas.ti software., Results: Patients' needs and expectations ranged across three overlapping areas: (i) prerequisites for getting online access; (ii) using online access; and (iii) the impact on interaction with healthcare providers. Patients expected benefits from online access such as better overview, empowerment and improved communication with their general practitioner but identified needs regarding technological difficulties, data privacy and complex medical language in their record., Conclusion: The concerns and obstacles participants identified point towards the need for organisational changes in general practice, for example, adjusted documentation practices, and the key role of the general practitioner and staff in promoting and facilitating online access., Implications: Implementation strategies addressing needs identified in this study may help to unlock the full potential of online access to achieve desired outcomes of patient involvement and satisfaction., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Using the Motivational Theory of Role Modelling as a framework, this study explores which attributes nurses deem essential for an effective peer champion, particularly in digital transformation processes within hospitals., Methods: A qualitative study was conducted with semi-structured interviews. Transcripts were coded using a hybrid approach of inductive and deductive coding and analysed using thematic analysis., Results: Ten nurses from Germany participated. The attributes most often mentioned were competence, taking on responsibility, a positive and passionate attitude, transferring knowledge and supporting aspirants in applying it, and leadership skills. Four types of champions were identified: a pragmatic and structured champion, a passionate innovator, a social and outgoing team leader, and a calm and empathetic team leader., Conclusions: The findings largely align with the body of literature on peer champion characteristics in other populations and should therefore be used to guide peer champion application in hospitals to enhance effective implementation of innovations., Innovation: The identification of four unique champion types offers an innovative contribution to the field. Highlighting the unique requirements of nurses when implementing innovative technologies in healthcare, this study emphasises the importance of involving end-users in the design and implementation process of new technologies, a crucial step towards a more sustainable and user-centred digital health ecosystem., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in the paper. The authors confirm all patient/personal identifiers have been removed or disguised so the patient/person(s) described are not identifiable and cannot be identified through the details of the story., (© 2024 The Authors.)

Objective: Online access to medical records is expected to foster patient empowerment and patient-centred healthcare. However, data on actual experienced effects remain limited. We aimed to examine the development of effects patients perceive from online access., Methods: A nationwide online survey (N = 1769) evaluated Dutch patients' use of online access and beliefs about its effects on 16 outcomes at baseline and one-year follow-up. Analyses of Variance (ANOVA) were used to examine within-person belief changes across three user groups: patients who 1) used online access before the study, 2) started use during the study, and 3) did not use it at all., Results: There was a small decline in five beliefs around online access facilitating patient empowerment and participation in participants who started using online access during the study compared to at least one other user group. Most changes in beliefs did not differ between groups., Conclusion: No evidence of benefits from online access was found. The findings might indicate inadequacies in the current system of online access. Possibly, the benefits of online access are contingent upon portal improvements and changes in documentation practices., Practice Implication: Records need to be easily accessible and comprehensible for patients. Consultation practices should enable patient participation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Late detection of oral cancer (OC) cases in Saudi Arabia is concerning. It reduces survival rate and complicates treatment. The ISAC intervention was developed to bridge the gaps observed in dentists' practice of OC examination and patient education. The ISAC stands for I, informing patients of OC screenings; S, screening for OC; A, advising high-risk patients to quit risk factors; and C, connecting patients to advanced services. This study tested the potential effect of the ISAC in influencing dentists' cognitive and behavioral skills, to enhance early detection and prevention of OC. A quasi-experimental study was conducted among dental interns (DIs) at dental setting to test the effect on comprehensive oral cancer examination score (COCE), awareness, self-efficacy, descriptive-norms, and self-reported behavior. Data were collected through triangulation of methods pre and post the intervention at two-months. Multiple linear mixed effects regression models were utilized for data analysis. Between October 2020 and April 2021, 47 DIs participated in the study. The final model showed the significant effects of time (ISAC) on COCE (95% CI = 25.12-29.42, P < .001). DIs had a significant improvement in awareness, self-efficacy, descriptive norms, and self-reported behavior. The findings showed promising effects of the intervention toward the early detection and prevention of OC. Dentists, dental organizations, and policymakers in areas with a high risk of OC could benefit from the current intervention which contributes to capacity building and improved community health. A pragmatic study with a robust design is needed to test the effectiveness of the intervention on a wider scale., (© 2023. The Author(s).)

Background: Patient online access to medical records is assumed to facilitate patient empowerment and advance patient-centered health care. However, to date, the actual effects of online access to medical records perceived by patients and other outcomes are insufficiently empirically tested., Objective: This study aimed to investigate the effects of online access to medical records on patient empowerment, informed decision-making, and the patient-provider relationship perceived by patients., Methods: A nationwide, 2-wave, longitudinal survey study was conducted among Dutch adults (N=2402). Linear regression analyses were performed. In model 1, the perceived effects of online access to medical records (measured at T1 [first measurement; July 2021]) on 16 outcomes (measured at T2 [second measurement; January 2022]), which were associated with the use of online access to general practice medical records in previous research, were investigated. Model 2 included sociodemographic factors and patient characteristics as confounders., Results: Users indicated more strongly than nonusers that online access to medical records would increase their participation in health care, improve the relationship with their general practitioner, and support informed decision-making. These results were robust when adjusted for the influence of confounders. Effect sizes were very small, with unstandardized regression coefficients (B) ranging between -0.39 and 0.28. Higher digital and health literacy were associated with higher ratings of almost all effects., Conclusions: Online access to medical records has the potential to empower patients and foster informed decision-making among patients. The effects in this study were small but might grow over time. Other factors, such as the attitude of general practitioners toward online access to medical records, might moderate these effects. The results indicate that the potential benefits of online access to medical records might be unevenly distributed. We suggest future exploration of the conditions under which online access to medical records can improve health care system functioning and efficiency without increasing health inequality., (©Rosa R L C Thielmann, Ciska Hoving, Jochen W L Cals, Rik Crutzen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.06.2023.)

Background: Although individually tailored eHealth programmes have shown to be effective in changing patient and citizen health behaviours, they have so far not been applied to lifestyle counselling guideline adherence in primary health care professionals beyond our STAR project. The programme aimed to support general practice nurses adhering to national smoking cessation counselling guidelines and showed encouraging positive impacts on both nurse and patient level., Objective: To identify lessons learned from our successful application of a tailored eHealth programme in primary health care., Methods: Triangulation of information from different sources collected throughout the project run time (e.g., project meetings, discussions with experts in the fields of computer tailoring, smoking cessation and professional education and interactions with general practice nurses)., Results: We identify four lessons learned which developers and testers of tailored eHealth programmes in primary health care should consider, relating to 1) Choosing outcome measures, 2) Measuring outcomes, 3) Practical feedback application & Programme accessibility, and 4) Programme interaction., Practice Implications: We share this information in the hope that we will see more applications of this promising intervention strategy - that can build on our work - in the future., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Unprotected sex is common among university students in Sudan, thus increasing risks for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV). As little is known about the psychosocial determinants of consistent condom use among this population, this study was designed to identify them. The Integrated Change Model (ICM) was applied in a cross-sectional design to identify in 218 students (aged 18-25 years) from Khartoum which items distinguish condom users from non-condom users. Condom users differed significantly from non-condom users in having more HIV and condom use-related knowledge, higher perception of susceptibility to HIV, reporting more exposure to condom use cues, having a less negative attitude towards condom use (attitude cons), experiencing social support and norms favouring condom use and having higher condom use self-efficacy. Binary logistic regression showed that peer norms favouring condom use in addition to HIV-related knowledge, condom use cues, negative attitude and self-efficacy were the factors uniquely associated with consistent condom use among university students in Sudan. Interventions seeking to promote consistent condom use among sexually active students could benefit from increasing knowledge about HIV transmission and prevention, raising HIV-risk perception, using condom use cues, addressing perceived condom disadvantages and enhancing students` self-efficacy to avoid unprotected sex. Moreover, such interventions should raise students` perceptions of their peers` beliefs and behaviours favouring condom use and seek health care professionals` and religious scholars` support for condom use., (© 2023. The Author(s).)

The objective was to assess active ingredients, change mechanisms, and fidelity in interventions aiming to increase the quality of smoking cessation care in the Dutch primary healthcare setting. We conducted a systematic review searching five scientific databases on August 2nd, 2019, updated on October 28th, 2021. We included effect data of behavioural interventions aiming at improving the provision of smoking cessation support by Dutch primary care providers to their patients. We excluded studies published before 2000 and those without a behavioural support intervention for primary care providers targeting smoking cessation in their patients. We found 1939 articles and included 15 distinct interventions in the review. We provided an overview of study characteristics, intervention effects, fidelity, active ingredients and change mechanisms using the Behaviour Change Techniques (BCT) Taxonomy and Mechanisms of Action (MoAs) protocols. Interventions seemed more effective when including a face-to-face component, using active learning strategies and providing a tool to help follow the guidelines in practice (e.g., physical cards with information). BCTs, MoAs, and fidelity were overall poorly reported on. To support the application of smoking cessation practices in Dutch primary care, we recommend implementation of face-to-face training programs incorporating active skill training elements combined with practical tools.

Evidence of economic evaluations of behaviour change interventions is scarce, but needed to guide policy makers' decision-making. This study economically evaluated 4 versions of an innovative online computer-tailored smoking cessation intervention. The economic evaluation from a societal perspective was embedded in a randomized controlled trial among 532 smokers using a 2 (message frame-tailoring, i.e. how messages are presented: autonomy-supportive vs controlling) x 2 (content-tailoring, i.e. what content is presented: tailored vs. generic) design. Both kinds of tailoring, content-tailoring and message frame-tailoring, were based on a set of questions asked at baseline. Self-reported costs, prolonged smoking abstinence (cost-effectiveness) and quality of life (cost-utility) were assessed during a 6-month-follow-up. For cost-effectiveness analysis, costs per abstinent smoker were calculated. For cost-utility analysis, costs per QALY (i.e. quality-adjusted life year) gained were calculated. A willingness-to-pay (WTP) threshold of €20.000 was used. Bootstrapping and sensitivity analysis were conducted. Cost-effectiveness analysis showed that up to a WTP of €2.000, the combination of message frame- and content-tailoring dominated all study groups. From a WTP of €2.005, the content-tailored group dominated all study groups. Cost-utility analysis revealed that the combination of message frame-tailoring and content-tailoring had the highest probability of being the most efficient study group at all levels of the WTP. The combination of message frame-tailoring and content-tailoring in online smoking cessation programmes seemed to have high potential for cost-effectiveness (smoking abstinence) and cost-utility (quality of life), thus providing good value for money. Yet, when the WTP for each abstinent smoker is high (i.e., €2.005 or higher), the addition of message frame-tailoring might not be worth the effort and content-tailoring only is preferred., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Altendorf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Smoking continues to be a driver of mortality. Various forms of evidence-based cessation assistance exist; however, their use is limited. The choice between them may also induce decisional conflict. Offering decision aids (DAs) may be beneficial; however, insights into their effective elements are lacking., Objective: This study tested the added value of an effective element (ie, an "explicit value clarification method" paired with computer-tailored advice indicating the most fitting cessation assistance) of a web-based smoking cessation DA., Methods: A web-based randomized controlled trial was conducted among smokers motivated to stop smoking within 6 months. The intervention group received a DA with the aforementioned elements, and the control group received the same DA without these elements. The primary outcome measure was 7-day point prevalence abstinence 6 months after baseline (time point 3 [t=3]). Secondary outcome measures were 7-day point prevalence of abstinence 1 month after baseline (time point 2 [t=2]), evidence-based cessation assistance use (t=2 and t=3), and decisional conflict (immediately after DA; time point 1). Logistic and linear regression analyses were performed to assess the outcomes. Analyses were conducted following 2 (decisional conflict) and 3 (smoking cessation) outcome scenarios: complete cases, worst-case scenario (assuming that dropouts still smoked), and multiple imputations. A priori sample size calculation indicated that 796 participants were needed. The participants were mainly recruited on the web (eg, social media). All the data were self-reported., Results: Overall, 2375 participants were randomized (intervention n=1164, 49.01%), of whom 599 (25.22%; intervention n=275, 45.91%) completed the DAs, and 276 (11.62%; intervention n=143, 51.81%), 97 (4.08%; intervention n=54, 55.67%), and 103 (4.34%; intervention n=56, 54.37%) completed time point 1, t=2, and t=3, respectively. More participants stopped smoking in the intervention group (23/63, 37%) than in the control group (14/52, 27%) after 6 months; however, this was only statistically significant in the worst-case scenario (crude P=.02; adjusted P=.04). Effects on the secondary outcomes were only observed for smoking abstinence after 1 month (15/55, 27%, compared with 7/46, 15%, in the crude and adjusted models, respectively; P=.02) and for cessation assistance uptake after 1 month (26/56, 46% compared with 18/47, 38% only in the crude model; P=.04) and 6 months (38/61, 62% compared with 26/50, 52%; crude P=.01; adjusted P=.02) but only in the worst-case scenario. Nonuse attrition was 34.19% higher in the intervention group than in the control group (P<.001)., Conclusions: Currently, we cannot confidently recommend the inclusion of explicit value clarification methods and computer-tailored advice. However, they might result in higher nonuse attrition rates, thereby limiting their potential. As a lack of statistical power may have influenced the outcomes, we recommend replicating this study with some adaptations based on the lessons learned., Trial Registration: Netherlands Trial Register NL8270; https://www.trialregister.nl/trial/8270., International Registered Report Identifier (irrid): RR2-10.2196/21772., (©Thomas Gültzow, Eline Suzanne Smit, Rik Crutzen, Shahab Jolani, Ciska Hoving, Carmen D Dirksen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.07.2022.)

Process evaluations help to understand and refine health interventions. The "ISAC" intervention targeted the enhancement of early detection and prevention of oral cancer (OC) through tobacco-cessation counseling, patient communications, and ISAC role-modeling. Over six months, throughout ISAC implementation in the Jazan region of Saudi Arabia, Linnan and Steckler's process evaluation framework's specified indicators were assessed, by mixed methods, on context, reach, dose delivered, dose received, fidelity, recruitment, and participant's satisfaction. Findings showed that 47 of 80 (58.75%) eligible dentists were reached and received all components. Thirty-six (76.6%) participants reported reading all intervention materials, visited the ISAC website, scored high on the perceived quality of provided information (M = 4.62 ± 0.63), and provided support (M = 4.67 ± 0.57). The fidelity was scored high across all intervention components. Role-modeling of the ISAC had the highest satisfaction score (M = 9.77 ± 0.58 out of 10). High perceived-effects were reported in relation to feeling confident in performing OC examination and training patients on OC self-examination (3.95 ± 0.22). The intervention attained high implementation levels for dose delivered, dose received, and fidelity. The intervention delivery was associated with high satisfaction and perceived effects. Using multiple data sources enhanced the understanding of the implementation process and strengthened the validity of the study's findings.

Background: Message frame-tailoring based on the need for autonomy is a promising strategy to improve the effectiveness of digital health communication interventions. An example of a digital health communication intervention is Personal Advice in Stopping smoking (PAS), a web-based content-tailored smoking cessation program. PAS was effective in improving cessation success rates, but its effect sizes were small and disappeared after 6 months. Therefore, investigating whether message frame-tailoring based on the individual's need for autonomy might improve effect rates is worthwhile. However, to our knowledge, this has not been studied previously., Objective: To investigate whether adding message frame-tailoring based on the need for autonomy increases the effectiveness of content-tailored interventions, the PAS program was redesigned to incorporate message frame-tailoring also. This paper described the process of redesigning the PAS program to include message frame-tailoring, providing smokers with autonomy-supportive or controlling message frames-depending on their individual need for autonomy. Therefore, we aimed to extend framing theory, tailoring theory, and self-determination theory., Methods: Extension of the framing theory, tailoring theory, and self-determination theory by redesigning the PAS program to include message frame-tailoring was conducted in close collaboration with scientific and nonscientific smoking cessation experts (n=10), smokers (n=816), and communication science students (n=19). Various methods were used to redesign the PAS program to include message frame-tailoring with optimal usability: usability testing, think-aloud methodology, heuristic evaluations, and a web-based experiment., Results: The most autonomy-supportive and controlling message frames were identified, the cutoff point for the need for autonomy to distinguish between people with high and those with low need for autonomy was determined, and the usability was optimized., Conclusions: This resulted in a redesigned digital health communication intervention that included message frame-tailoring and had optimal usability. A detailed description of the redesigning process of the PAS program is provided., Trial Registration: Netherlands Trial Register NL6512 (NRT6700); https://www.trialregister.nl/trial/6512., (©Inge S van Strien-Knippenberg, Maria B Altendorf, Ciska Hoving, Julia C M van Weert, Eline S Smit. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.04.2022.)

Background: Evidence-based smoking cessation interventions provided by healthcare professionals can be successful in helping citizens to quit smoking. Yet, evidence is needed about the active ingredients of these interventions, how these ingredients work and how they are implemented in practice. Such knowledge is required to effectively support healthcare professionals to optimally put evidence-based smoking cessation interventions to (inter)national practice., Objective: To identify active ingredients (including behavior change techniques), mechanisms of action and implementation fidelity reported in smoking cessation interventions in Dutch primary care settings and to relate these to intervention effectiveness., Methods: A systematic review was conducted by searching nine national intervention or funding databases, five international scientific databases and consulting 17 national smoking cessation experts. Out of 1066 identified manuscripts, 40 interventions were eligible for this review. Based on published protocols, information regarding behavior change techniques and mechanisms of action was systematically abstracted. Additionally, information regarding study characteristics and other active ingredients, effects on smoking behavior and implementation fidelity was abstracted. Comparative effectiveness concerning abstracted intervention characteristics was qualitatively explored., Results: Active ingredients, mechanisms of action and implementation fidelity were moderately to poorly reported. Interventions applying behavior change techniques and interventions with a single behavioral target (i.e. smoking-only versus multiple behaviors) seemed to provide stronger evidence for successfully changing smoking behavior., Conclusion: Attention to and reporting on interventions' active ingredients (e.g. behavior change techniques), mechanisms of action and implementation fidelity are prerequisites for developing more effective evidence-based smoking cessation interventions to be successfully implemented in primary healthcare., Implications: This systematic review provides an overview of smoking cessation interventions in Dutch primary care settings, identified since the year 2000. Smoking cessation support is offered in various forms, but our qualitative findings show that interventions including more behavior change techniques and interventions targeting only smoking cessation (compared to multiple behaviors) might be more effective. Results also show that-based on available intervention reports-it is difficult to distinguish patterns of active ingredients (such as behavior change techniques), mechanisms of action and fidelity of implementation in relation to interventions' effectiveness. This means (quality of) reporting on these intervention characteristics should improve., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Objective: We aimed to explore dentists' perceptions toward the implementation of a comprehensive intervention (ISAC) for the early detection and prevention of oral cancer in a dental clinic., Methods: The ISAC intervention was presented to ten purposefully sampled dentists in Jazan Dental School (JDS). Participating dental interns were asked to practice the ISAC intervention whilst thinking aloud. A semi-structured interview technique was used to allow free expression of participants' perceptions related to the ISAC intervention and to control the flow of topics. Fleuren's framework theory informed the analysis. The interviews were transcribed verbatim and analyzed using the deductive-inductive framework analysis., Results: Practicing the ISAC intervention was perceived to enhance the early detection and prevention of oral cancer. Serving community needs and engaging community groups were perceived to be related to a high relevance and compatibility of the ISAC intervention. Being a comprehensive intervention with well-defined objectives and being built on relevant data from the participants' community and having dentists as a target group were the perceived relative advantages of the ISAC intervention compared to other programs. A supportive environment, gender-concordance, use of regional trainers, standard examination form and collaboration with other sectors were perceived to be the facilitators. Competition with clinical time, use of different examination forms and low organizational leader interests were perceived as impeding factors against effective implementation in a real-world context. Reward, easy to practice, feeling confidence and satisfaction, advertisement as well as use of a role model approach were perceived to be motivating factors., Conclusions: Integrating data from representers of different participant groups during intervention conceptualization and development are critical for the intervention compatibility and acceptability. The study findings showed the opportunities of intertwining the intrinsic motivators of satisfaction and altruism existing in the target group and the extrinsic motivator of official diagnostic skill, certification that may boost and sustain the behavior change. Intervention features that influence perceived relevance, compatibility, relative advantage and motivation may be of great importance for intervention practice., (© 2022. The Author(s).)

The use of evidence-based smoking cessation interventions (SCIs) can significantly increase the number of successful smoking cessation attempts. To obtain an overview of the knowledge and viewpoints on the effectiveness and use of SCIs, a three-round online Delphi study was conducted among researchers and primary care professionals (PCPs). The four objectives of this study are to gain an overview of (i) the criteria important for recommending SCIs, (ii) the perceptions of both groups on the effectiveness of SCIs, (iii) the factors to consider when counseling different (high-risk) groups of smokers and (iv) the perceptions of both groups on the use of e-cigarettes as an SCI. We found a high level of agreement within groups on which smoker characteristics should be considered when recommending an SCI to smokers. We also found that PCPs display a lower degree of consensus on the effectiveness of SCIs. Both groups see a value in the use of special protocols for different (high-risk) groups of patients, but the two groups did not reach consensus on the use of e-cigarettes as a means to quit. Making an inventory of PCPs' needs regarding SCIs and their usage may provide insight into how to facilitate a better uptake in the primary care setting., (© The Author(s) 2021. Published by Oxford University Press.)

University students in Sudan are more at risk of contracting HIV than the general population, due to a high rate of sexual activity and low uptake of preventive measures such as condoms. Hence, they are considered an important target for HIV prevention programmes. This study explored students` beliefs about abstinence and pre-marital sex. Thirty semi-structured individual interviews were conducted, based on constructs from the Integrated Change (I-Change) Model. The study sample included 16 (53%) male and 14 (47%) female university students. Their average age was 21.2 years (Range 18-27 and SD 2.5). Both sexual abstainers ( N  = 19) and sexually active students ( N  = 11) perceived HIV severity and susceptibility. Most of the participants had a positive attitude towards abstinence. However, sexually active students also perceived some advantages of engaging in sexual practices, such as sexual pleasure and proving adulthood. Sexually active students more often mentioned being influenced in their sexual practices by their peers than by their families. Sexually active students reported lower self-efficacy to refrain from sex than abstainers. Interventions that seek to promote abstinence among those willing to achieve this should stress the advantages of abstinence from sex until marriage, offer tools to resist peer pressure and enhance self-efficacy to abstain. These findings can be used to develop comprehensive HIV prevention programmes that primarily promote abstinence among university students who are not yet sexually active but also consider promoting condom use and other safer-sex practices among those who are sexually active. These interventions should also be gender-sensitive to address the needs of both male and female students.

Objective: Numerous decision aids (DAs) have been developed to inform pregnant people about prenatal screening as the decision whether or not to accept the prenatal screening offer may be difficult. Currently, little is known about the role of the decisional partner of the pregnant people in this decision-making process and to what extent DAs involve and engage the partner., Methods: A broad search was conducted to identify publicly available DAs in English and/or Dutch regarding prenatal screening and diagnosis. These DAs were analysed on aspects of partner involvement., Results: Ten of the 19 identified DAs (52.6%) contained at least one aspect of partner involvement. Several DAs acknowledged that both partners should be involved in the decision (n = 7). The content that was least likely to contain aspects of partner involvement in the DA was value clarification content (n = 2) and only one DA contained content with plural addressing., Conclusion: Just over half of the included DAs included some aspect(s) of partner involvement., Practical Implications: More research is needed to determine to what extent, and how, the partner should be involved in the decision-making process as expectant people consider the input of their partner as important., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to authorship and/or publication of this article., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

People make numerous health-related choices each day: For example, deciding to brush one's teeth or to eat well and healthy - or not to do these activities. To support complex decisions and subsequent behaviour change, both Behaviour Change Interventions (BCIs) and Patient Decision Aids (PtDAs) have been developed and evolved independently to support people in health-related decision making. In this paper, we critically review BCIs and PtDAs, examine their similarities and differences, and identify potential for integration of expertise to increase the benefits for people engaging with healthcare and health behaviours. The two approaches appear to mainly differ in terms of their (1) goals and foci, (2) theoretical basis, (3) development frameworks, (4) active ingredients and (5) effect evaluation. To facilitate the integration of scientific insights from these two fields, we recommend to (1) bring both fields together and promote interprofessional discussions, (2) train (health) professionals to recognise strengths of both approaches, (3) investigate the synergy of the two fields, (4) be prepared for and try to mitigate a culture shock when the fields start to interact. Knowledge generated by researching PtDAs could be used to facilitate decisional processes that enable patients to choose goals that are in line with their values and preferences, while insights from researching BCIs could be used to facilitate engagement with, and implementation of those goals. This integration could allow researchers and intervention providers to increase the benefits for people engaging with healthcare and health behaviours., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This review aimed to identify the behavioral change techniques (BCTs) used in behavioral interventions for tobacco cessation at dental practices in relation to their effect on tobacco use. Six scientific databases were searched for behavior change interventions for tobacco cessation and were coded using the BCT taxonomy of behavioral support for smoking cessation (BCTTsm). Fifteen interventions were identified, and data related to intervention characteristics were abstracted. Sixteen BCTs were identified, mainly related to increased motivation and teaching regulatory skills. Goal setting was the most commonly used BCT. Ten out of fifteen interventions effectively impacted tobacco cessation outcomes (OR = 2 to 5.25). Effective interventions more frequently included goal setting, written materials, readiness to quit and ability assessment, tobacco-use assessment, self-efficacy boost, listing reasons for quitting, action planning and environment restructuring. Other BCTs were not clearly associated with an increased effect. Among the behavioral interventions, certain techniques were associated with successful tobacco quitting. Tobacco cessation interventions in a dental setting appear to benefit from using BCTs that increase motivation and teach regulatory skills. The identified BCTs in this review could provide a source to better inform researchers and dentists about the active ingredients in behavior change interventions for tobacco cessation in a dental setting.

Objective: To broadly synthesize literature regarding decision aids (DAs) supporting decision making about diet, physical activity, sleeping and substance use a scoping review was performed., Methods: Multiple sources were used: (1) Scientific literature searches, (2) excluded references from a Cochrane review regarding DAs for treatments and screenings, and (3) results from additional searches. Interventions had to (1) support informed decision making and (2) provide information and help to choose between at least two options. Two researchers screened titles and abstracts. Relevant information was extracted descriptively., Results: Thirty-five scientific articles and four DAs (grey literature) were included. Results were heterogeneous. Twenty-nine (94%) studies described substance use DAs. All DAs offered information and value and/or preference clarification. Many other elements were included (e.g., goal-setting). DA's effects were mixed. Few studies used standardized measures, e.g., decisional conflict (n = 4, 13%). Some positive behavioral effects were reported: e.g., smoking abstinence (n = 1)., Conclusions: This research shows only some positive behavioral effects of DAs. However, studies reported heterogeneous results/outcomes, impeding knowledge synthesis. Areas of improvement were identified, e.g., establishing which intervention elements are effective regarding health behavior decision making., Practice Implications: DAs can potentially be beneficial in supporting people to change health behaviors - especially regarding smoking., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To test the effect of autonomy-supportive message framing on people's perceived autonomy-support while considering the individual need for autonomy as a moderator. Also, to test whether autonomy-supportive message frames - through increased perceived autonomy-support - lead to more self-determined motivation, and increased intention to quit smoking., Design: An online 2(autonomy-supportive; controlling language) × 2(choice; no choice) between-subjects design with control condition (generic advice) with adult smokers intending to quit ( N  = 626)., Main Outcome: Intention to quit smoking (Theory of Planned Behaviour)., Measures: Perceived autonomy-support (Virtual Climate Care Questionnaire), need for autonomy (Health Causality Orientations Scale), self-determined motivation (Treatment Self-Regulation Questionnaire), attitudes, social influence, self-efficacy (I-Change Model)., Results: Structural equation modelling revealed no significant effect of autonomy-supportive-message frames on perceived autonomy-support or self-determined motivation, neither did the need for autonomy moderate these effects. Self-determined motivation had a positive, significant effect on intention to quit, mediated by attitudes, social influence, and self-efficacy., Conclusion: Although message frames did not affect perceived autonomy-support or self-determined motivation, higher self-determined motivation increased intention to quit via attitudes, social influence, and self-efficacy. Before drawing the conclusion that message framing has no effect, we recommend to replicate this study in a real-life setting with smokers more likely to read and process the message frames more attentively.

Background: Adherence to core type 2 diabetes mellitus (T2DM) treatment behaviors is suboptimal, and nonadherence is generally not limited to one treatment behavior. The internet holds promise for programs that aim to improve adherence. We developed a computer-tailored eHealth program for patients with T2DM to improve their treatment adherence, that is, adherence to both a healthy lifestyle and medical behaviors., Objective: The objective of this study is to examine the effectiveness of the eHealth program in a randomized controlled trial., Methods: Patients with T2DM were recruited by their health professionals and randomized into either the intervention group, that is, access to the eHealth program for 6 months, or a waiting-list control group. In total, 478 participants completed the baseline questionnaire, of which 234 gained access to the eHealth program. Of the 478 participants, 323 were male and 155 were female, the mean age was 60 years, and the participants had unfavorable BMI and HbA 1c levels on average. Outcome data were collected through web-based assessments on physical activity (PA) levels, caloric intake from unhealthy snacks, and adherence to oral hypoglycemic agents (OHAs) and insulin therapy. Changes to separate behaviors were standardized and summed into a composite change score representing changes in the overall treatment adherence. Further standardization of this composite change score yielded the primary outcome, which can be interpreted as Cohen d (effect size). Standardized change scores observed in separate behaviors acted as secondary outcomes. Mixed linear regression analyses were conducted to examine the effectiveness of the intervention on overall and separate treatment behavior adherence, accommodating relevant covariates and patient nesting., Results: After the 6-month follow-up assessment, 47.4% (111/234) of participants in the intervention group and 72.5% (177/244) of participants in the control group were retained. The overall treatment adherence improved significantly in the intervention group compared with the control group, reflected by a small effect size (d=0.27; 95% CI 0.032 to 0.509; P=.03). When considering changes in separate treatment behaviors, a significant decrease was observed only in caloric intake from unhealthy snacks in comparison with the control group (d=0.36; 95% CI 0.136 to 0.584; P=.002). For adherence to PA (d=-0.14; 95% CI -0.388 to 0.109; P=.27), OHAs (d=0.27; 95% CI -0.027 to 0.457; P=.08), and insulin therapy (d=0.35; 95% CI -0.066 to 0.773; P=.10), no significant changes were observed. These results from the unadjusted analyses were comparable with the results of the adjusted analyses, the per-protocol analyses, and the sensitivity analyses., Conclusions: Our multibehavior program significantly improved the overall treatment adherence compared with the control group. To further enhance the impact of the intervention in the personal, societal, and economic areas, a wide-scale implementation of our eHealth intervention is suggested., Trial Registration: Netherlands Trial Register NL664; https://www.trialregister.nl/trial/6664., (©Stan Vluggen, Math Candel, Ciska Hoving, Nicolaas C Schaper, Hein de Vries. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.02.2021.)

Objectives: Evidence-based smoking cessation support tools (EBSTs) can double the quitting chances, but uptake among smokers is low. A digital decision aid (DA) could help smokers choose an EBST in concordance with their values and preferences, but it is unclear which type of smokers are interested in a digital DA. We hypothesized that smokers' general decision-making style (GDMS) could be used to identify early adopters. This study therefore aimed to identify smoker profiles based on smokers' GDMS and investigate these profiles' association with intention to use a digital DA., Design: A cross-sectional dataset (N = 200 smokers intending to quit) was used to perform a hierarchical cluster analysis based on smokers' GDMS scores., Methods: Clusters were compared on demographic and socio-cognitive variables. Mediation analyses were conducted to see if the relationship between cluster membership and intention was mediated through socio-cognitive variables (e.g., attitude)., Results: Two clusters were identified; " Avoidant Regretters " (n = 134) were more avoidant, more regretful and tended to depend more on others in their decision making, while " Intuitive Non-regretters " (n = 66) were more spontaneous and intuitive in their decision making. Cluster membership was significantly related to intention to use a DA, with " Avoidant Regretters " being more interested. Yet, this association ceased to be significant when corrected for socio-cognitive variables (e.g., attitude). This indicates that cluster membership affected intention via socio-cognitive variables., Conclusions: The GDMS can be used to identify smokers who are interested in a digital DA early on. As such, the GDMS can be used to tailor recruitment and DA content., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Decision aids (DAs) may be used to facilitate an autonomous, informed decision to cease smoking and promote the uptake of evidence-based cessation assistance (ie, behavioral support, nicotine replacement therapy, or prescription medication). However, knowledge is lacking regarding their effective elements and (cost-)effectiveness., Objective: We describe the development process of an online DA (called "VISOR") that helps smokers to choose evidence-based cessation assistance. Additionally, we provide a description of the protocol of an ongoing randomized controlled trial in which the DA containing an explicit value clarification method (VCM) and tailored advice is compared with a DA without an explicit VCM and tailored advice., Methods: The development of "VISOR" was based on the International Patient Decision Aid Standards guidelines. Viewpoints of end users (collected through 20 interviews with smokers) and clinical and scientific experts (assessed using 2 Delphi studies with 24 scientists and 38 clinicians) were assessed regarding cessation tool decision making and preferred DA content. These findings, together with principles from the Self-Determination Theory, served as input for the development of the online DA. A first DA prototype was alpha-tested in September 2019 and beta-tested for usability in December 2019; feedback was incorporated and resulted in a final version. The final DA contains (1) an information section, (2) an optional knowledge quiz, (3) a brief smoking assessment, (4) intuitive decision, (5) intermediate advice, (6) an explicit VCM, (7) tailored advice, and (8) access information. A randomized controlled trial is currently being conducted to assess the DA's (cost-)effectiveness compared to a DA that does not include the explicit VCM and the tailored advice; specifically, the DA's effect on smoking abstinence, uptake of evidence-based cessation assistance, smoking abstinence mediated through uptake of evidence-based cessation assistance, and decisional conflict are investigated. Participants are randomly allocated to receive access to 1 of the 2 DAs and are asked to complete 5 questionnaires (including the baseline questionnaire) over a period of 12 months. To evaluate the effects of the DA on the outcome measures, logistic and linear regression analyses as well as mediation analyses will be carried out. An economic evaluation will be performed to assess the cost-effectiveness., Results: Data regarding the effect of the VISOR DA are currently being collected, and data collection is expected to be concluded in 2021., Conclusions: By making use of an iterative process that integrated different stakeholders' perspectives (including end users), we were able to systematically design an evidence-based DA. The study will contribute to the current knowledge regarding smoking cessation DA application, the added value of explicit VCMs, and the effect of behavioral and informed decision-making outcomes., Trial Registration: Netherlands Trial Register NL8270; https://www.trialregister.nl/trial/8270., International Registered Report Identifier (irrid): DERR1-10.2196/21772., (©Thomas Gültzow, Eline Suzanne Smit, Raesita Hudales, Vera Knapen, Jany Rademakers, Carmen D Dirksen, Ciska Hoving. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.12.2020.)

Background: Effective recruitment of patients by health professionals is challenging but pivotal to the success of clinical trials. Many trials fail to include the required number of participants, which affects the power of the study, generalizability of results, and timely dissemination of positive outcomes. Existing research is inconclusive regarding factors influencing recruitment results, and most research does not focus on perceptions of recruiting health professionals themselves. Therefore, thorough evaluations of recruitment facilitators and barriers in trials are needed in order to optimize future patient recruitment in trials. We observed divergent recruitment results among nurses who recruited diabetes patients to our trial, which examined the effectiveness of an eHealth programme. Therefore, we aimed to describe nurses' recruitment results and related shifts over time, and to qualitatively explore factors influencing nurses' recruitment results., Methods: Nurses' recruitment results and related temporal shifts were derived from trial data (NTR6840). Based on their recruitment results, nurses were categorized as non-, low-, medium-, or high-recruiters. Subsequently, a subset of nurses per group participated in an individual semi-structured telephone interview. Interviews were analysed using NVivo software, applying an inductive coding approach., Results: Ninety-six nurses participated in our trial and recruited on average seven patients (range: 0-32). Fifteen nurses did not recruit any patients. Most patients were recruited close to recruitment onset. Nurses who did not recruit patients close to recruitment onset generally ended up recruiting no patients. Data show a relatively high number of early recruited patients that progressively declined over time. High-recruiters were generally successful throughout the entire recruitment period. Recruitment facilitators and barriers comprised organizational, study, patient, and especially recruiter characteristics. Contrary to non- and low-recruiters, medium- and high-recruiters reported more in-depth knowledge about the study and trial requirements, expressed more personal participation-related benefits and fewer barriers, and incorporated more recruitment activities, reminders, and barrier-focused coping strategies., Conclusion and Implications: To optimize patient recruitment to clinical trials, suggested intervention targets include the continued inclusion of recruiters after initial recruitment onset and the encouragement of early recruitment success. A personalized approach may aid recruiters to become and remain successful. Primarily, it is important to provide recruiters with sufficient information on trial requirements and to address salient benefits for participation in the trial, both for themselves and for their patients. Finally, teaching recruiters skills on how to overcome barriers may further enhance motivation and recruitment capacities.

Increasing numbers of university students in Sudan are at risk of contracting HIV because of their engagement in condomless sex. A comprehensive and culturally accepted condom promotion program could potentially reduce this threat substantially. However, little is known about the sociocognitive determinants of condom use in this population: information that is required to develop such HIV prevention programs. Therefore, in August 2014, we conducted 30 semi-structured individual interviews with male and female students (both currently sexually active and nonactive) to explore determinants of condom use based on the I-Change model. Data were analyzed using Nvivo 10. The results suggest that barriers to condom use among university students include misconceptions about condom use, negative attitudes toward condom use, lack of social support, low self-efficacy to use condoms, and poor action planning. Sexual health promotion should, therefore, address these aspects to successfully promote condom use among sexually active students and subsequently reduce the risk of HIV transmission.