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Background: In recent years, the effectiveness and cost-effectiveness of digital health services for people with musculoskeletal conditions have increasingly been studied and show potential. Despite the potential of digital health services, their use in primary care is lagging. A thorough implementation is needed, including the development of implementation strategies that potentially improve the use of digital health services in primary care. The first step in designing implementation strategies that fit the local context is to gain insight into determinants that influence implementation for patients and health care professionals. Until now, no systematic overview has existed of barriers and facilitators influencing the implementation of digital health services for people with musculoskeletal conditions in the primary health care setting., Objective: This systematic literature review aims to identify barriers and facilitators to the implementation of digital health services for people with musculoskeletal conditions in the primary health care setting., Methods: PubMed, Embase, and CINAHL were searched for eligible qualitative and mixed methods studies up to March 2024. Methodological quality of the qualitative component of the included studies was assessed with the Mixed Methods Appraisal Tool. A framework synthesis of barriers and facilitators to implementation was conducted using the Consolidated Framework for Implementation Research (CFIR). All identified CFIR constructs were given a reliability rating (high, medium, or low) to assess the consistency of reporting across each construct., Results: Overall, 35 studies were included in the qualitative synthesis. Methodological quality was high in 34 studies and medium in 1 study. Barriers (-) of and facilitators (+) to implementation were identified in all 5 CFIR domains: "digital health characteristics" (ie, commercial neutral [+], privacy and safety [-], specificity [+], and good usability [+]), "outer setting" (ie, acceptance by stakeholders [+], lack of health care guidelines [-], and external financial incentives [-]), "inner setting" (ie, change of treatment routines [+ and -], information incongruence (-), and support from colleagues [+]), "characteristics of the healthcare professionals" (ie, health care professionals' acceptance [+ and -] and job satisfaction [+ and -]), and the "implementation process" (involvement [+] and justification and delegation [-]). All identified constructs and subconstructs of the CFIR had a high reliability rating. Some identified determinants that influence implementation may be facilitators in certain cases, whereas in others, they may be barriers., Conclusions: Barriers and facilitators were identified across all 5 CFIR domains, suggesting that the implementation process can be complex and requires implementation strategies across all CFIR domains. Stakeholders, including digital health intervention developers, health care professionals, health care organizations, health policy makers, health care funders, and researchers, can consider the identified barriers and facilitators to design tailored implementation strategies after prioritization has been carried out in their local context., (©Mark Leendert van Tilburg, Ivar Spin, Martijn F Pisters, J Bart Staal, Raymond WJG Ostelo, Miriam van der Velde, Cindy Veenhof, Corelien JJ Kloek. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.08.2024.)

Background: Providing individualized care based on the context and preferences of the patient is important. Knowledge on both prognostic risk stratification and blended eHealth care in musculoskeletal conditions is increasing and seems promising. Stratification can be used to match patients to the most optimal content and intensity of treatment as well as mode of treatment delivery (i.e. face-to-face or blended with eHealth). However, research on the integration of stratified and blended eHealth care with corresponding matched treatment options for patients with neck and/or shoulder complaints is lacking., Methods: This study was a mixed methods study comprising the development of matched treatment options, followed by an evaluation of the feasibility of the developed Stratified Blended Physiotherapy approach. In the first phase, three focus groups with physiotherapists and physiotherapy experts were conducted. The second phase investigated the feasibility (i.e. satisfaction, usability and experiences) of the Stratified Blended Physiotherapy approach for both physiotherapists and patients in a multicenter single-arm convergent parallel mixed methods feasibility study., Results: In the first phase, matched treatment options were developed for six patient subgroups. Recommendations for content and intensity of physiotherapy were matched to the patient's risk of persistent disabling pain (using the Keele STarT MSK Tool: low/medium/high risk). In addition, selection of mode of treatment delivery was matched to the patient's suitability for blended care (using the Dutch Blended Physiotherapy Checklist: yes/no). A paper-based workbook and e-Exercise app modules were developed as two different mode of treatment delivery options, to support physiotherapists. Feasibility was evaluated in the second phase. Physiotherapists and patients were mildly satisfied with the new approach. Usability of the physiotherapist dashboard to set up the e-Exercise app was considered 'OK' by physiotherapists. Patients considered the e-Exercise app to be of 'best imaginable' usability. The paper-based workbook was not used., Conclusion: Results of the focus groups led to the development of matched treatment options. Results of the feasibility study showed experiences with integrating stratified and blended eHealth care and have informed amendments to the Stratified Blended Physiotherapy approach for patients with neck and/or shoulder complaints ready to use within a future cluster randomized trial., (© 2023. The Author(s).)

Background: Neck and shoulder complaints are common in primary care physiotherapy. These patients experience pain and disability, resulting in high societal costs due to, for example, healthcare use and work absence. Content and intensity of physiotherapy care can be matched to a patient's risk of persistent disabling pain. Mode of care delivery can be matched to the patient's suitability for blended care (integrating eHealth with physiotherapy sessions). It is hypothesized that combining these two approaches to stratified care (referred to from this point as Stratified Blended Approach) will improve the effectiveness and cost-effectiveness of physiotherapy for patients with neck and/or shoulder complaints compared to usual physiotherapy., Methods: This paper presents the protocol of a multicenter, pragmatic, two-arm, parallel-group, cluster randomized controlled trial. A total of 92 physiotherapists will be recruited from Dutch primary care physiotherapy practices. Physiotherapy practices will be randomized to the Stratified Blended Approach arm or usual physiotherapy arm by a computer-generated random sequence table using SPSS (1:1 allocation). Number of physiotherapists (1 or > 1) will be used as a stratification variable. A total of 238 adults consulting with neck and/or shoulder complaints will be recruited to the trial by the physiotherapy practices. In the Stratified Blended Approach arm, physiotherapists will match I) the content and intensity of physiotherapy care to the patient's risk of persistent disabling pain, categorized as low, medium or high (using the Keele STarT MSK Tool) and II) the mode of care delivery to the patient's suitability and willingness to receive blended care. The control arm will receive physiotherapy as usual. Neither physiotherapists nor patients in the control arm will be informed about the Stratified Blended Approach arm. The primary outcome is region-specific pain and disability (combined score of Shoulder Pain and Disability Index & Neck Pain and Disability Scale) over 9 months. Effectiveness will be compared using linear mixed models. An economic evaluation will be performed from the societal and healthcare perspective., Discussion: The trial will be the first to provide evidence on the effectiveness and cost-effectiveness of the Stratified Blended Approach compared with usual physiotherapy in patients with neck and/or shoulder complaints., Trial Registration: Netherlands Trial Register: NL8249 . Officially registered since 27 December 2019. Date of first enrollment: 30 September 2020. Study status: ongoing, data collection.

Background: Medically unexplained physical symptoms (MUPS) are a leading cause of reduced work functioning. It is not known which factors are associated with reduced work functioning in people with moderate MUPS. Insight in these factors can contribute to prevention of reduced work functioning, associated work-related costs and in MUPS becoming chronic. Therefore, the aim of this study was to identify which demographic and health-related factors are associated with reduced work functioning, operationalized as impaired work performance and absenteeism, in people with moderate MUPS., Methods: Data of 104 participants from an ongoing study on people with moderate MUPS were used in this cross-sectional study. Ten independent variables were measured at baseline to determine their association with reduced work functioning: severity of psychosocial symptoms (four domains, measured with the Four-Dimensional Symptom Questionnaire), physical health (RAND 36-Item Health Survey), moderate or vigorous physical activity (Activ8 activity monitor), age, sex, education level and duration of complaints. Two separate multivariable linear regression analyses were performed with backward stepwise selection, for both impaired work performance and absenteeism., Results: Absenteeism rate rose with 2.5 and 0.6% for every increased point on the Four-Dimensional Symptom Questionnaire for domain 'depression' (B = 0.025, SE = 0.009, p = .006) and domain 'somatization' (B = 0.006, SE = 0.003, p = .086), respectively. An R 2 value of 0.118 was found. Impaired work performance rate rose with 0.2 and 0.5% for every increased point on the Four-Dimensional Symptom Questionnaire for domain 'distress' (B = 0.002, SE = 0.001, p = .084) and domain 'somatization' (B = 0.005, SE = 0.001, p < .001), respectively. An R 2 value of 0.252 was found., Conclusions: Severity of distress, probability of a depressive disorder and probability of somatization are positively associated with higher rates of reduced work functioning in people with moderate MUPS. To prevent long-term absenteeism and highly impaired work performance severity of psychosocial symptoms seem to play a significant role. However, because of the low percentage of explained variance, additional research is necessary to gain insight in other factors that might explain the variance in reduced work functioning even better.

We demonstrated previously that mucosal immunization of mice with Streptococcus mutans coated with the monoclonal antibody (MAb) 6-11A directed against the major surface adhesin protein P1 results in changes in the amount, isotype distribution, and specificity of serum antibodies compared with animals immunized with bacteria only. We now show that the specificity of the mucosal secretory IgA response was also influenced by this MAb. Changes in antibody specificity were associated with changes in biological activity. Serum samples which differed in antibody reactivity with P1 polypeptides generated by partial digestion with N-chlorosuccinimide but not in isotype distribution or overall reactivity with S. mutans or intact P1 demonstrated a statistically significant difference in the ability to inhibit bacterial adherence to salivary-agglutinin-coated hydroxyapatite beads. Serum IgG antibodies against P1 from mice immunized with either S. mutans alone or S. mutans coated with 6-11A were shown to recognize antigenic determinants dependent on the presence of the central proline-rich repeat domain, a segment necessary for the structural integrity of the molecule. However, no statistically significant differences were observed in antibody reactivity with a panel of six partial P1 polypeptides encoded by overlapping spaP subclones, suggesting that the targets of biologically relevant antibodies involve complex epitopes not reconstituted by the recombinant products tested. Lastly, we show that binding of MAb 6-11A to P1 on the surface of S. mutans alters P1's susceptibility to proteolytic digestion. Hence, changes in antigen processing and presentation may contribute to the immunomodulatory effects of this MAb.

Systemic immunization with antigen coupled to monoclonal antibody (MAb) has been used by several investigators to increase the number of MAb-producing hybridomas against an antigen and to elicit antibodies specific for poorly immunogenic epitopes. This strategy has implications for vaccine design in that protective immunity is not necessarily directed at immunodominant epitopes of pathogens and may be improved by deliberately shifting the immune response toward subdominant epitopes. To our knowledge, no studies to date have addressed the potential for immunomodulatory activity mediated by MAbs bound to mucosally applied antigen. To test whether administration of an exogenous MAb directed against a streptococcal surface protein could influence the humoral immune response, BALB/c mice were immunized orally by gastric intubation or intranasally with Streptococcus mutans alone or S. mutans complexed with a MAb directed against the major surface protein P1. Significant changes in the subclass distribution, as well as the specificity, of anti-P1 serum immunoglobulin G antibodies were demonstrated in groups of mice which received S. mutans coated with the anti-P1 MAb versus those which received S. mutans alone. Alterations in the humoral immune response were dependent on the amount of anti-P1 MAb used to coat the bacteria. In addition, differences in the anti-P1 immune responses were observed between groups of mice immunized via oral versus intranasal routes. In summary, an exogenous MAb complexed with a streptococcal antigen prior to mucosal immunization can influence the immunoglobulin isotype and specificity of the host humoral immune response against the antigen.