Pre-implementation planning for a sepsis intervention in a large learning health system: a qualitative study.

BACKGROUND: Sepsis survivors experience high morbidity and mortality. Though recommended best practices have been established to address the transition and early post hospital needs and promote recovery for sepsis survivors, few patients receive recommended post-sepsis care. Our team developed the Sepsis Transition and Recovery (STAR) program, a multicomponent transition intervention that leverages virtually-connected nurses to coordinate the application of evidence-based recommendations for post-sepsis care with additional clinical support from hospitalist and primary care physicians. In this paper, we present findings from a qualitative pre-implementation study, guided by the Consolidated Framework for Implementation Research (CFIR), of factors to inform successful STAR implementation at a large learning health system prior to effectiveness testing as part of a Type I Hybrid trial. METHODS: We conducted semi-structured qualitative interviews (n = 16) with 8 administrative leaders and 8 clinicians. Interviews were transcribed and analyzed in ATLAS.ti using a combination deductive/inductive strategy based on CFIR domains and constructs and the Constant Comparison Method. RESULTS: Six facilitators and five implementation barriers were identified spanning all five CFIR domains (Intervention Characteristics, Outer Setting, Inner Setting, Characteristics of Individuals and Process). Facilitators of STAR included alignment with health system goals, fostering stakeholder engagement, sharing STAR outcomes data, good communication between STAR navigators and patient care teams/PCPs, clinician promotion of STAR with patients, and good rapport and effective communication between STAR navigators and patients, caregivers, and family members. Barriers of STAR included competing demands for staff time and resources, insufficient communication and education of STAR's value and effectiveness, underlying informational and technology gaps among patients, lack of patient access to community resources, and patient distrust of the program and/or health care. CONCLUSIONS: CFIR proved to be a robust framework for examining facilitators and barriers for pre-implementation planning of post-sepsis care programs within diverse hospital and community settings in a large LHS. Conducting a structured pre-implementation evaluation helps researchers design with implementation in mind prior to effectiveness studies and should be considered a key component of Type I hybrid trials when feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04495946 . Registered August 3, 2020.

Implementation of Coach McLungsSM into primary care using a cluster randomized stepped wedge trial design.

BACKGROUND: Asthma is a prevalent chronic disease that is difficult to manage and associated with marked disparities in outcomes. One promising approach to addressing disparities is shared decision making (SDM), a method by which the patient and provider cooperatively make a decision about asthma care. SDM is associated with improved outcomes for patients; however, time constraints and staff availability are noted implementation barriers. Use of health information technology (IT) solutions may facilitate the utilization of SDM. Coach McLungsSM is a collaborative web-based application that involves pediatric patients, their caregivers, and providers in a personalized experience while gathering patient-reported data. Background logic provides decision support so both audiences can develop a well-informed treatment plan together. The goal of this study is to evaluate the implementation of the Coach McLungsSM intervention into primary care. METHODS: Implementation will be evaluated using a stepped wedge randomized control study design at 21 pediatric and family medicine practices within a large, integrated, nonprofit healthcare system. We will measure changes in emergency department visits, hospitalizations, and oral steroid use, which serve as surrogate measures for patient-centered asthma outcomes. We will use a generalized linear mixed models with logit link to test the hypothesis for the reduction in exacerbation rates specifying the fixed effects of intervention and time and random effects for practice and practice*time. This design achieves 84% power to detect the hypothesized effect size difference of 10% in overall exacerbation between control (40%) and intervention (30%) periods (two-sided, p = 0.05). Implementation will be guided using the Expert Recommendations for Implementing Change (ERIC), a compilation of implementation strategies, and evaluated using the CFIR (Consolidated Framework for Implementation Research) and RE-AIM (Reach Effectiveness, Adoption, Implementation, Maintenance). DISCUSSION: We anticipate that a tailored implementation of Coach McLungsSM across diverse primary care practices will lead to a decrease in emergency department visits, hospitalizations, and oral steroid use for patients in the intervention group as compared to the control condition. TRIAL REGISTRATION: Clincaltrials.gov, NCT05059210. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059210.

Protocol for a two-arm pragmatic stepped-wedge hybrid effectiveness-implementation trial evaluating Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship (ENCOMPASS).

BACKGROUND: Sepsis survivors experience high morbidity and mortality, and healthcare systems lack effective strategies to address patient needs after hospital discharge. The Sepsis Transition and Recovery (STAR) program is a navigator-led, telehealth-based multicomponent strategy to provide proactive care coordination and monitoring of high-risk patients using evidence-driven, post-sepsis care tasks. The purpose of this study is to evaluate the effectiveness of STAR to improve outcomes for sepsis patients and to examine contextual factors that influence STAR implementation. METHODS: This study uses a hybrid type I effectiveness-implementation design to concurrently test clinical effectiveness and gather implementation data. The effectiveness evaluation is a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial at eight hospitals in North Carolina comparing clinical outcomes between sepsis survivors who receive Usual Care versus care delivered through STAR. Each hospital begins in a Usual Care control phase and transitions to STAR in a randomly assigned sequence (one every 4 months). During months that a hospital is allocated to Usual Care, all eligible patients will receive usual care. Once a hospital transitions to STAR, all eligible patients will receive STAR during their hospitalization and extending through 90 days from discharge. STAR includes centrally located nurse navigators using telephonic counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted with suspected sepsis, defined by clinical criteria for infection and organ failure, are included. Planned enrollment is 4032 patients during a 36-month period. The primary effectiveness outcome is the composite of all-cause hospital readmission or mortality within 90 days of discharge. A mixed-methods implementation evaluation will be conducted before, during, and after STAR implementation. DISCUSSION: This pragmatic evaluation will test the effectiveness of STAR to reduce combined hospital readmissions and mortality, while identifying key implementation factors. Results will provide practical information to advance understanding of how to integrate post-sepsis management across care settings and facilitate implementation, dissemination, and sustained utilization of best-practice post-sepsis management strategies in other heterogeneous healthcare delivery systems. TRIAL REGISTRATION: NCT04495946 . Submitted July 7, 2020; Posted August 3, 2020.

Adult intravenous sedation in general dental practice: indication, effectiveness and patient experiences.

Background Conscious sedation is an option in primary dental care for anxious patients or those undergoing extensive procedures. The objective of this retrospective service evaluation was to study the range of treatments delivered during sedation with intravenous midazolam, together with patient-reported experience measures.Methods Data from 100 consecutive patients treated under sedation at a single private dental practice were evaluated retrospectively. All patients were asked questions about their experience of sedation during a post-operative follow-up phone call.Results Over half of patients were treated under sedation due to anxiety. The mean dose of midazolam was 7.8 mg and the average treatment time was 1 hour 25 minutes. Of note, the average dose for the most extensive procedure - implant immediate full arch loading - was 11.7 mg; however, this equated to an average dose of 4.5 mg per hour. One patient needed supplemental oxygen; flumazenil was never required. Additionally, 91% of patients felt they had enough sedation, and 50% could remember the events of treatment.Conclusion With the British National Formulary recommending a maximum dose of 7.5 mg midazolam, this study demonstrates that this dose can be safely exceeded in dental treatment; therefore, a dose that accounts for the length of the procedure is a more valid approach. Moreover, patients undergoing a variety of dental treatments were satisfied with the amount of intravenous sedation received and age is not an absolute limit for sedating older people.

Implementation of nurse-initiated rapid HIV testing at high-prevalence primary care sites within the U.S. Veterans Affairs Health Care System.

Nurse-initiated HIV rapid testing (NRT) increases testing/receipt of results compared with traditional testing. We implemented NRT in primary care clinics at 2 Veterans Affairs hospitals.At site 1, 2364 tests were conducted; 5 HIV positives were identified. At site 2, 2522 tests were conducted; 9 HIV positives were identified. Success varied across demographic/clinical strata.

Immediately loaded full arch implant rehabilitation and oral health-related quality of life: A retrospective cohort study from primary dental care.

AIMS: This study evaluates patient-centered outcomes in patients undergoing full-arch rehabilitation, with immediate loading of implants. Using the Oral Health Impact Profile questionnaire pre-and post-treatment, it assesses the hypothesis that immediate full arch loading significantly improves quality of life. METHODOLOGY: A dataset was defined as: 20 consecutive patients from a research database who had undergone IFAL surgery (maxilla, mandible, or both) and definitive restoration by a single clinician, and completed the OHIP-14 questionnaire prior to treatment and after restoration. RESULTS: Pre (T0 ) and post (T1 ) treatment questionnaires were analyzed from 20 consecutive patients in whom a total of 160 implants were placed. The mean T0 score was 26.7, and mean T1 score 4.6. Differences were statistically significant (p = 0.00008). Greatest improvements were seen in psychological discomfort and disability, and pain. Worsening quality of life was shown by questions relating to speech in six patients and taste in three patients. CONCLUSION: This study demonstrates that overall IFAL significantly improves tooth-related quality of life. It suggests reasons for patients to seek treatment while providing evidence to manage expectations, such as possible implications on speech, thus supporting informed consent of future patients in a primary care setting.

A Multidisciplinary Diabetes Clinic Improves Clinical and Behavioral Outcomes in a Primary Care Setting.

The percentage of adults achieving hemoglobin A1c goals less than 7% remains a challenge. The study objective was to evaluate effects of a multidisciplinary approach on behavioral outcomes and mean change in A1c in immediate start (intervention) versus 6-month delay (control) groups at 6 months. The study assessed 111 patients recruited from a safety-net primary care clinic with a pharmacist-led multidisciplinary team and found that the intervention improved mean A1c outcomes for patients with type 2 diabetes. A1c values were measured every 3 months, and a self-efficacy scale to measure behaviors was evaluated at baseline and 6 months. After 6 months from baseline, the intervention group showed an A1c decrease of 2.4 compared with the control group's 1.1 decrease. Mean increase in self-efficacy score in the intervention group at baseline versus after 6 months showed a statistically significant change (P = .01) compared with the control group (P = .26). Results revealed a post hoc association between A1c and PHQ-9 such that patients with higher baseline PHQ-9 scores experienced greater mean decrease in A1c. In the immediate start arm, mean A1c values decreased from 10.6 at baseline to 7.7 at month 12. For the delayed intervention group, mean A1c values decreased from 10.2 at baseline to 9.0 after 6 months.

Evaluation of a dental nurse-led triage system in a private dental practice during the COVID-19 pandemic.

Objectives To evaluate a dental nurse-led triage system at a private dental practice in England after the cessation of face-to-face care during the COVID-19 pandemic; to assess types of presenting problems and their management upon practice reopening at alert level 4; and to explain the benefits of dental nurse-led triage and its relevance to other practices.Methods This retrospective service evaluation used anonymised data gathered for the purpose of assessing and triaging patients when they could not be seen face-to-face. Effectiveness of the triage system was assessed using predetermined criteria.Results Seventy patients were triaged during a 12-week period; 68.5% of patients were managed by the triaging dental nurse without escalation to a dentist and 77% of patients called only once. The most common presenting complaint was pain, followed by loose crown/bridge and fractured crown/tooth/bridge. Sixty-one percent of all patients accepted a face-to-face appointment upon reopening of the dental practice.Conclusions This study demonstrates the effectiveness of a dental nurse-led triage model where dental nurses have the skills and experience required to manage patients at first contact. This model would be applicable to other practices in the case of future emergency closures, as well as a routine out-of-hours service.

Evaluation of a shared decision-making intervention for pediatric patients with asthma in the emergency department.

BACKGROUND: Asthma is a difficult-to-manage chronic disease marked with associated outcome disparities including an increase rate of emergency department (ED) visits for uncontrolled asthma among patients who are most at-risk. Shared decision making (SDM) is a process by which the patient and provider jointly make a healthcare choice. SDM improves patient outcomes; however, implementation barriers of time constraints and staff availability are limitations. The use of health IT solutions may increase the adoption of SDM, but best practices for implementation are not well understood. The Consolidated Framework for Implementation Research (CFIR) is a flexible comprehensive model used to identify barriers and facilitators influencing implementation. The goal of this study is to implement an innovative web-based pediatric SDM tool in the real-world setting of two large healthcare system EDs through the following aims: (1) convene a patient, research, and ED stakeholder advisory board to oversee review of protocol and study materials prior to implementation, (2) implement the SDM intervention where providers and staff will be trained to incorporate use of this SDM intervention, (3) conduct on-going evaluation of barriers, facilitators, and implementation outcomes to tailor implementation in the EDs, (4) evaluate patient-centered outcomes of primary care utilization and changes in ED visits and hospitalizations before and after the SDM intervention, and (5) understand and document best practices for ED implementation. METHODS: The CFIR model will guide the implementation evaluation. Researchers will administer surveys to the clinical team and patients at baseline, 3, 6, and 12 months to inform implementation design, determine barriers and facilitators, and resource-needs to allow for real-time process adjustments within the EDs. Focus group or key-informant interviews and analysis will provide additional feedback to the stakeholder team to iterate the implementation process. Researchers will track patient-centered outcomes including increased primary care, ED, and inpatient utilization over the duration of the study. DISCUSSION: To advance asthma care and the field of implementation science, further research is needed to assess best practices for incorporating SDM into high-need healthcare settings such as the ED. This knowledge will facilitate improved outcomes and appropriate policy changes towards further use of SDM interventions in local and national acute care settings.

Tipping the scales: Provider perspectives on a multi-disciplinary approach to obesity.

IMPACT STATEMENT: Obesity is a major multi-faceted, chronic disease that increases the risk of morbidity and mortality of children and adults particularly impacting high-risk populations and those of lower socioeconomic status. Given provider time constraints, models of care to effectively and efficiently address obesity in primary care are key. Although physician recommendations can exert a powerful influence on behavior, providers often feel powerless to adequately address obesity due to the complexity of physical and behavioral health problems. This mini-review focuses on describing the feasibility and evidence for tackling obesity through provider-led multidisciplinary weight management programs.

Sustaining nurse-rapid HIV testing in the U.S. Department of Veterans Affairs: lessons learned from a comparative evaluation.

Routine HIV testing in primary care is now recommended in the United States. The U.S. Department of Veterans Affairs (VA) has increased the number of patients tested for HIV, but overall HIV testing rates remain low. A promising intervention for increasing HIV testing is nurse-initiated rapid testing (NRT). The purpose of this study was to build upon our previous research by implementing NRT in primary care clinics at two geographically distinct VA medical centers, and then conduct an evaluation to identify the barriers and facilitators to implementing and sustaining it. Semistructured telephone interviews were conducted with providers and stakeholders at two VA medical centers, one each on the East Coast and in the Southwest. Fieldnotes were developed following each interview and qualitatively coded for emerging themes. Findings indicate NRT was well integrated in both settings. NRT took little time to conduct, was well received by patients, and did not disrupt clinical scheduling. However, there were some sustainability challenges, including difficulties using the electronic medical record, and the challenges of new care practice structures. Implementing NRT is feasible in VA primary care settings. However, organizational challenges should be taken into account for subsequent efforts to implement NRT in VA primary care settings.

Exercise capacity and progression from prehypertension to hypertension.

Prehypertension is likely to progress to hypertension. The rate of progression is determined mostly by age and resting blood pressure but may also be attenuated by increased fitness. A graded exercise test was performed in 2303 men with prehypertension at the Veterans Affairs Medical Centers in Washington, DC. Four fitness categories were defined, based on peak metabolic equivalents (METs) achieved. We assessed the association between exercise capacity and rate of progression to hypertension (HTN). The median follow-up period was 7.8 years (mean (± SD) 9.2±6.1 years). The incidence rate of progression from prehypertension to hypertension was 34.4 per 1000 person-years. Exercise capacity was a strong and independent predictor of the rate of progression. Compared to the High-Fit individuals (>10.0 METs), the adjusted risk for developing HTN was 66% higher (hazard ratio, 1.66; 95% CI, 1.2 to 2.2; P=0.001) for the Low-Fit and, similarly, 72% higher (hazard ratio, 1.72; 95% CI, 1.2 to 2.3; P=0.001) for the Least-Fit individuals, whereas it was only 36% for the Moderate-Fit (hazard ratio, 1.36; 95% CI, 0.99 to 1.80; P=0.056). Significant predictors for the progression to HTN were also age (19% per 10 years), resting systolic blood pressure (16% per 10 mm Hg), body mass index (15.3% per 5 U), and type 2 diabetes mellitus (2-fold). In conclusion, an inverse, S-shaped association was shown between exercise capacity and the rate of progression from prehypertension to hypertension in middle-aged and older male veterans. The protective effects of fitness were evident when exercise capacity exceeded 8.5 METs. These findings emphasize the importance of fitness in the prevention of hypertension.

Induction of thymocyte positive selection does not convey immediate resistance to negative selection.

The acquisition of functional competence represents a critical phase during intrathymic development of T cells. Thymocytes reaching this stage represent cells which have been positively selected on the basis of major histocompatibility complex reactivity, but which have also been purged of potentially autoreactive T-cell receptor specificities by negative selection. While the developmental window in which thymocytes are subjected to positive selection is now well defined, the precise developmental timing of negative selection, in relation to positive selection events, is less clear. Moreover, the underlying mechanism allowing single-positive thymocytes to respond to T-cell receptor ligation by activation rather than death, remains controversial. Here we have analysed the developmental timing of negative selection in relation to positive selection, using measurement of thymocyte susceptibility to dendritic cell presentation of the superantigen staphylococcal enterotoxin B (SEB). We show that thymocytes which have received initial positive selection signals, namely CD4+ CD8+ CD69+ thymocytes, like their CD4+ CD8+ CD69minus sign precursors, are susceptible to negative selection, indicating that induction of positive selection does not convey immediate resistance to negative selection. In contrast, newly generated CD4+ CD8minus sign CD69+ cells are not only resistant to deletion by SEB, but respond to SEB-mediated T-cell receptor-ligation by activation, indicating that the acquisition of functional competence occurs at the newly generated CD4+ CD8minus sign CD69+ stage. Finally, by using direct retroviral infection of primary CD4+ CD8+ thymocytes, we also show that Notch-1 activation in CD4+ CD8+ thymocytes does not correlate with, nor convey resistance to superantigen-mediated negative selection. Thus, our data suggest that although Notch-1 has been implicated in resistance to thymocyte apoptosis, the acquisition of resistance to negative selection occurs independently of Notch-1 signalling.

Modeling TCR signaling complex formation in positive selection.

T cell receptor signaling in the thymus can result in positive selection, and hence progressive maturation to the CD4(+)8(-) or CD4(-)8(+) stage, or induction of apoptosis by negative selection. Although it is poorly understood how TCR ligation at the CD4(+)8(+) stage can lead to such different cell fates, it is thought that the strength of signal may play a role in determining the outcome of TCR signaling. In this study, we have characterized the formation of an active signaling complex in thymocytes undergoing positive selection as a result of interaction with thymic epithelial cells. Although this signaling complex involves redistribution of cell surface and intracellular molecules, reminiscent of that observed in T cell activation, accumulation of GM1-containing lipid rafts was not observed. However, enforced expression of the costimulatory molecule CD80 on thymic epithelium induced GM1 polarization in thymocytes, and was accompanied by reduced positive selection and increased apoptosis. We suggest that the presence or absence of CD80 costimulation influences the outcome of TCR signaling in CD4(+)8(+) thymocytes through differential lipid raft recruitment, thus determining overall signal strength and influencing developmental cell fate.

Thymic epithelial cells provide WNT signals to developing thymocytes.

Interactions with thymic stromal cells are known to be critical for the development of T cells from progenitors entering the thymus, yet the molecular mechanisms of stromal cell function remain poorly understood. Accumulating evidence has highlighted the importance of beta-catenin-mediated activation of T cell factor (TCF)/lymphoid enhancer factor (LEF) transcription during thymocyte development. As regulation of this signaling pathway is controlled by binding of soluble Wnt proteins to cell surface Frizzled (Fz) receptors, we studied components of Wnt/Fz-mediated signaling in thecontext of stromal cell regulation of thymocyte development. We show that mRNA for a variety of Wnt family members, notably Wnt-4, Wnt-7a and 7b, and Wnt-10a and 10b, are expressed by thymic epithelium rather then by thymocytes, while thymocytes demonstrate a developmentally regulated pattern of Fz receptor expression. Collectively these findings suggest (1) a functional role for Wnt-producing thymic epithelium in determining TCF/LEF-mediated transcriptional regulation in Fz-bearing thymocytes, and (2) a role for defined Wnt-Fz interactions at successive stages of thymocyte maturation. In support of this we show that separation of thymocytes from Wnt-producing epithelial cells and the thymic microenvironment, triggers beta-catenin phosphorylation and degradation in thymocytes. Thus, sustained exposure to Wnt in the context of an intact stromal microenvironment is necessary for stabilization of beta-catenin-mediated signaling in thymocytes.

Cutting edge: a chemical genetic system for the analysis of kinases regulating T cell development.

To understand the regulatory activities of kinases in vivo requires their study across a biologically relevant window of activity. To this end, ATP analog-sensitive kinase alleles (ASKAs) specifically sensitive to a competitive inhibitor have been developed. This article tests whether ASKA technology can be applied to complex immunological systems, such as lymphoid development. The results show that when applied to reaggregate thymic organ culture, novel p56(Lck) ASKAs readily expose a dose-dependent correlation of thymocyte development with a range of p56(Lck) activity. By regulating kinase activity, rather than amounts of RNA or protein, ASKA technology offers a general means for assessing the quantitative contributions to immunology of numerous kinases emerging from genomics analyses. It can obviate the generation of multiple lines of mice expressing different levels of kinase transgenes and should permit specific biological effects to be associated with defined biochemical activities.