Factors influencing the implementation of early discharge hospital at home and admission avoidance hospital at home: a qualitative evidence synthesis.

BACKGROUND: Worldwide there is an increasing demand for Hospital at Home as an alternative to hospital admission. Although there is a growing evidence base on the effectiveness and cost-effectiveness of Hospital at Home, health service managers, health professionals and policy makers require evidence on how to implement and sustain these services on a wider scale. OBJECTIVES: (1) To identify, appraise and synthesise qualitative research evidence on the factors that influence the implementation of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home, from the perspective of multiple stakeholders, including policy makers, health service managers, health professionals, patients and patients' caregivers. (2) To explore how our synthesis findings relate to, and help to explain, the findings of the Cochrane intervention reviews of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home services. SEARCH METHODS: We searched MEDLINE, CINAHL, Global Index Medicus and Scopus until 17 November 2022. We also applied reference checking and citation searching to identify additional studies. We searched for studies in any language. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with qualitative data collection and analysis methods examining the implementation of new or existing Hospital at Home services from the perspective of different stakeholders. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, extracted study characteristics and intervention components, assessed the methodological limitations using the Critical Appraisal Skills Checklist (CASP) and assessed the confidence in the findings using GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research). We applied thematic synthesis to synthesise the data across studies and identify factors that may influence the implementation of Hospital at Home. MAIN RESULTS: From 7535 records identified from database searches and one identified from citation tracking, we included 52 qualitative studies exploring the implementation of Hospital at Home services (31 Early Discharge, 16 Admission Avoidance, 5 combined services), across 13 countries and from the perspectives of 662 service-level staff (clinicians, managers), eight systems-level staff (commissioners, insurers), 900 patients and 417 caregivers. Overall, we judged 40 studies as having minor methodological concerns and we judged 12 studies as having major concerns. Main concerns included data collection methods (e.g. not reporting a topic guide), data analysis methods (e.g. insufficient data to support findings) and not reporting ethical approval. Following synthesis, we identified 12 findings graded as high (n = 10) and moderate (n = 2) confidence and classified them into four themes: (1) development of stakeholder relationships and systems prior to implementation, (2) processes, resources and skills required for safe and effective implementation, (3) acceptability and caregiver impacts, and (4) sustainability of services. AUTHORS' CONCLUSIONS: Implementing Admission Avoidance and Early Discharge Hospital at Home services requires early development of policies, stakeholder engagement, efficient admission processes, effective communication and a skilled workforce to safely and effectively implement person-centred Hospital at Home, achieve acceptance by staff who refer patients to these services and ensure sustainability. Future research should focus on lower-income country and rural settings, and the perspectives of systems-level stakeholders, and explore the potential negative impact on caregivers, especially for Admission Avoidance Hospital at Home, as this service may become increasingly utilised to manage rising visits to emergency departments.

Implementation interventions to promote the uptake of evidence-based practices in stroke rehabilitation.

BACKGROUND: Rehabilitation based upon research evidence gives stroke survivors the best chance of recovery. There is substantial research to guide practice in stroke rehabilitation, yet uptake of evidence by healthcare professionals is typically slow and patients often do not receive evidence-based care. Implementation interventions are an important means to translate knowledge from research to practice and thus optimise the care and outcomes for stroke survivors. A synthesis of research evidence is required to guide the selection and use of implementation interventions in stroke rehabilitation. OBJECTIVES: To assess the effects of implementation interventions to promote the uptake of evidence-based practices (including clinical assessments and treatments recommended in evidence-based guidelines) in stroke rehabilitation and to assess the effects of implementation interventions tailored to address identified barriers to change compared to non-tailored interventions in stroke rehabilitation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and eight other databases to 17 October 2019. We searched OpenGrey, performed citation tracking and reference checking for included studies and contacted authors of included studies to obtain further information and identify potentially relevant studies. SELECTION CRITERIA: We included individual and cluster randomised trials, non-randomised trials, interrupted time series studies and controlled before-after studies comparing an implementation intervention to no intervention or to another implementation approach in stroke rehabilitation. Participants were qualified healthcare professionals working in stroke rehabilitation and the patients they cared for. Studies were considered for inclusion regardless of date, language or publication status. Main outcomes were healthcare professional adherence to recommended treatment, patient adherence to recommended treatment, patient health status and well-being, healthcare professional intention and satisfaction, resource use outcomes and adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and certainty of evidence using GRADE. The primary comparison was any implementation intervention compared to no intervention. MAIN RESULTS: Nine cluster randomised trials (12,428 patient participants) and three ongoing trials met our selection criteria. Five trials (8865 participants) compared an implementation intervention to no intervention, three trials (3150 participants) compared one implementation intervention to another implementation intervention, and one three-arm trial (413 participants) compared two different implementation interventions to no intervention. Eight trials investigated multifaceted interventions; educational meetings and educational materials were the most common components. Six trials described tailoring the intervention content to identified barriers to change. Two trials focused on evidence-based stroke rehabilitation in the acute setting, four focused on the subacute inpatient setting and three trials focused on stroke rehabilitation in the community setting. We are uncertain if implementation interventions improve healthcare professional adherence to evidence-based practice in stroke rehabilitation compared with no intervention as the certainty of the evidence was very low (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.53 to 2.64; 2 trials, 39 clusters, 1455 patient participants; I2 = 0%). Low-certainty evidence indicates implementation interventions in stroke rehabilitation may lead to little or no difference in patient adherence to recommended treatment (number of recommended performed outdoor journeys adjusted mean difference (MD) 0.5, 95% CI -1.8 to 2.8; 1 trial, 21 clusters, 100 participants) and patient psychological well-being (standardised mean difference (SMD) -0.02, 95% CI -0.54 to 0.50; 2 trials, 65 clusters, 1273 participants; I2 = 0%) compared with no intervention. Moderate-certainty evidence indicates implementation interventions in stroke rehabilitation probably lead to little or no difference in patient health-related quality of life (MD 0.01, 95% CI -0.02 to 0.05; 2 trials, 65 clusters, 1242 participants; I2 = 0%) and activities of daily living (MD 0.29, 95% CI -0.16 to 0.73; 2 trials, 65 clusters, 1272 participants; I2 = 0%) compared with no intervention. No studies reported the effects of implementation interventions in stroke rehabilitation on healthcare professional intention to change behaviour or satisfaction. Five studies reported economic outcomes, with one study reporting cost-effectiveness of the implementation intervention. However, this was assessed at high risk of bias. The other four studies did not demonstrate the cost-effectiveness of interventions. Tailoring interventions to identified barriers did not alter results. We are uncertain of the effect of one implementation intervention versus another given the limited very low-certainty evidence. AUTHORS' CONCLUSIONS: We are uncertain if implementation interventions improve healthcare professional adherence to evidence-based practice in stroke rehabilitation compared with no intervention as the certainty of the evidence is very low.

Protease-activated Receptor 1 Plays a Proinflammatory Role in Colitis by Promoting Th17-related Immunity.

BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR. The functional relevance of these clinical data was further studied in a mouse model of Citrobacter rodentium-induced colitis. RESULTS: PAR1 expression was significantly upregulated in the inflamed colons of pediatric patients with Crohn's disease, with expression levels directly correlating to disease severity. In patients with severe colitis, PAR1 expression uniquely correlated with Th17-related (IL17A, IL22, and IL23A) cytokines. Infection of PAR1-deficient (PAR1) and wildtype mice with colitogenic C. rodentium revealed that disease severity and colonic pathology were strongly attenuated in mice lacking PAR1. Furthermore, Th17-type immune response was completely abolished in the colons of infected PAR1 but not wildtype mice. Finally, PAR1 was shown to be essential for secretion of the Th17-driving cytokine IL-23 by C. rodentium-stimulated macrophages. CONCLUSIONS: This study demonstrates a strong link between PAR1 expression, Th17-type immunity, and disease severity in both pediatric patients with Crohn's disease and C. rodentium-induced colitis in mice. The data presented suggest PAR1 exerts a proinflammatory role in colitis in both humans and mice by promoting a Th17-type immune response, potentially by supporting the production of IL-23.

Activation of TRIF-dependent and independent immune responses by neisserial heat shock protein complex vaccines.

ASBTRACT Heat shock protein Complex (HspC) vaccines are composed of Hsp purified from pathogenic bacteria along with their chaperoned protein cargo. Mouse studies have shown that HspC vaccines can induce a strong immune response against pathogenic bacteria without addition of an exogenous adjuvant. These vaccines are now entering clinical trials. It was predicted, but not previously tested, that HspC vaccines induce an immune response due to the activation of Toll-Like Receptors (TLR) by their component Hsp. Recently we tested this supposition and found that while this held true for the cellular response to neisserial HspC vaccines, strong antigen-specific antibody responses were surprisingly generated in mice deficient in MyD88 and thus most TLR signaling. This suggested an unidentified mechanism by which HspC vaccines induce an antibody response. We have now examined the antigenic profile of this response and found no evidence that this is due to the induction of T-independent antibodies. Examination of the MyD88-dependent signaling pathways involved in the cellular response to neisserial HspC showed that both TRIF-dependent and TRIF-independent pathways are activated, each resulting in the secretion of different cytokines. Hence the mechanism of action of HspC vaccines is clearly more complicated than originally thought.

Heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism.

BACKGROUND: Neisseria meningitidis are common colonizers of the human nasopharynx. In some circumstances, N. meningitidis becomes an opportunistic pathogen that invades tissues and causes meningitis. While a vaccine against a number of serogroups has been in effective use for many years, a vaccine against N. meningitidis group B has not yet been universally adopted. Bacterial heat shock protein complex (HSPC) vaccines comprise bacterial HSPs, purified with their chaperoned protein cargo. HSPC vaccines use the intrinsic adjuvant activity of their HSP, thought to act via Toll-like receptors (TLR), to induce an immune response against their cargo antigens. This study evaluated HSPC vaccines from N. meningitidis and the closely related commensal N. lactamica. RESULTS: The protein composition of N. lactamica and N. meningitidis HSPCs were similar. Using human HEK293 cells we found that both HSPCs can induce an innate immune response via activation of TLR2. However, stimulation of TLR2 or TLR4 deficient murine splenocytes revealed that HSPCs can activate an innate immune response via multiple receptors. Vaccination of wildtype mice with the Neisseria HSPC induced a strong antibody response and a Th1-restricted T helper response. However, vaccination of mice deficient in the major TLR adaptor protein, MyD88, revealed that while the Th1 response to Neisseria HSPC requires MyD88, these vaccines unexpectedly induced an antigen-specific antibody response via a MyD88-independent mechanism. CONCLUSIONS: N. lactamica and N. meningitidis HSPC vaccines both have potential utility for immunising against neisserial meningitis without the requirement for an exogenous adjuvant. The mode of action of these vaccines is highly complex, with HSPCs inducing immune responses via both MyD88-dependent and -independent mechanisms. In particular, these HSPC vaccines induced an antibody response without detectable T cell help.

Heat shock protein complex vaccination induces protection against Helicobacter pylori without exogenous adjuvant.

BACKGROUND: The development of a vaccine against the human gastric pathogen Helicobacter pylori, the main causative agent of gastric adenocarcinoma, has been hampered by a number of issues, including the lack of a mucosal adjuvant for use in humans. Heat shock proteins (Hsp), highly conserved molecules expressed by both bacteria and mammalian species, possess a range of functions, including acting as chaperones for cellular proteins and the ability to activate innate immune receptors. Hsp complex (HspC) vaccines, containing Hsp derived from pathogenic bacteria, are immunostimulatory without addition of an exogenous adjuvant and can induce immunity against their chaperoned proteins. In this study we explored in mice the potential utility of a H. pylori HspC vaccine. RESULTS: Vaccination with H. pylori HspC, by either the subcutaneous or respiratory mucosal route, induced a strong antibody response, elevated gastric cytokine levels and significant protection against subsequent live challenge with this pathogen. The level of protection induced by non-adjuvanted HspC vaccine was equivalent to that which resulted from vaccination with adjuvanted vaccines. While protection induced by immunisation with adjuvanted vaccines was associated with the development of a moderate to severe atrophic gastritis, that induced by H. pylori HspC only resulted in a mild inflammatory response, despite an increase in pro-inflammatory gastric cytokines. This reduced gastritis correlated with an increase in IL-10 and IL-13 levels in the gastric tissues of HspC vaccinated, H. pylori challenged mice. CONCLUSIONS: H. pylori HspC vaccines have the potential to overcome some of the issues preventing the development of a human vaccine against this pathogen: HspC induced protective immunity against H. pylori without addition of an adjuvant and without the induction of a severe inflammatory response. However, complete protection was not obtained so further optimisation of this technology is needed if a human vaccine is to become a reality.