Core implementation strategies for improving cirrhosis care in the Veterans Health Administration.

BACKGROUND AND AIMS: The Veterans Health Administration (VHA) provides care for more than 80,000 veterans with cirrhosis. This longitudinal, multimethod evaluation of a cirrhosis care quality improvement program aimed to (1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and (2) use qualitative interviews to operationalize strategies for a manualized intervention. APPROACH AND RESULTS: VHA providers were surveyed annually about the use of 73 implementation strategies to improve cirrhosis care in fiscal years 2018 (FY18) and 2019 (FY19). Implementation strategies linked to guideline-concordant cirrhosis care were identified using bivariate statistics and comparative configurational methods. Semistructured interviews were conducted with 12 facilities in the highest quartile of cirrhosis care to specify the successful implementation strategies and their mechanisms of change. A total of 106 VHA facilities (82%) responded at least once over the 2-year period (FY18, n = 63; FY19, n = 100). Facilities reported using a median of 12 (interquartile range [IQR] 20) implementation strategies in FY18 and 10 (IQR 19) in FY19. Of the 73 strategies, 35 (48%) were positively correlated with provision of evidence-based cirrhosis care. Configurational analysis identified multiple strategy pathways directly linked to more guideline-concordant cirrhosis care. Across both methods, a subset of eight strategies was determined to be core to cirrhosis care improvement and specified using qualitative interviews. CONCLUSIONS: In a national cirrhosis care improvement initiative, a multimethod approach identified a core subset of successful implementation strategy combinations. This process of empirically identifying and specifying implementation strategies may be applicable to other implementation challenges in hepatology.

Balancing collaborative and independent practice roles in clinical pharmacy: a qualitative research study.

BACKGROUND: Clinical pharmacists (CPs) with a scope of practice operate as direct care providers and health care team members. Research often focuses on one role or the other; little is understood about the dynamic relationship between roles in practice settings. OBJECTIVE: To identify the challenges CPs face in balancing dual roles as direct care providers and health care team members and the implications for CP effectiveness and quality of care. METHODS: Pharmacists were interviewed with a primary purpose of informing an implementation effort. Besides the implementation, there were emergent themes regarding the challenges posed for CPs in negotiating dual roles. This study is, therefore, a secondary analysis of semistructured interviews and direct observation of 48 CPs, addressing this phenomenon. Interview data were entered into NVivo 10 and systematically analyzed using an emergent thematic coding strategy. RESULTS: Pharmacists describe role ambiguity, where they perform as direct providers or team members simultaneously or in quick succession. They note the existence of a "transaction cost," where switching causes loss of momentum or disruption of work flow. Additionally, pharmacists feel that fellow providers lack an understanding of what they do and that CP contributions are not evaluated accurately by other health professionals. CONCLUSION: It is a challenge for CPs to balance the distinct roles of serving as collaborators and primary providers. Frequent role switching is not conducive to optimal work efficiency or patient care. Our findings suggest concrete steps that medical centers can take to improve both CP worklife and quality of patient care.

The interplay of contextual elements in implementation: an ethnographic case study.

BACKGROUND: Contextual elements have significant impact on uptake of health care innovations. While existing conceptual frameworks in implementation science suggest contextual elements interact with each other, little research has described how this might look in practice. To bridge this gap, this study identifies the interconnected patterns among contextual elements that influence uptake of an anticoagulation clinic improvement initiative. METHODS: We completed 51 semi-structured interviews and ethnographic observations across five case study sites involved in an evidence-based practice (EBP) quality improvement initiative. We analyzed data in NVivo 10 using an a priori approach based on the Promoting Action on Research Implementation in Health Services (PARIHS) model and an emergent thematic analysis. RESULTS: Key contextual elements, such as leadership, teamwork, and communication, interacted with each other in contributing to site-level uptake of the EBP, often yielding results that could not be predicted by looking at just one of these elements alone. Sites with context conducive to change in these areas predictably had high uptake, while sites with uniformly weak contextual elements had low uptake. Most sites presented a mixed picture, with contextual elements being strongly supportive of change in some areas and weak or moderate in others. In some cases, we found that sites with strong context in at least one area only needed to have adequate context in other areas to yield high uptake. At other sites, weak context in just one area had the potential to contribute to low uptake, despite countervailing strengths. Even a site with positive views of EBPs could not succeed when context was weak. CONCLUSION: Interrelationships among different contextual elements can act as barriers to uptake at some sites and as facilitators at others. Accounting for interconnections among elements enables PARIHS to more fully describe the determinants of successful implementation as they operate in real-world settings.

Hepatitis C Care in the Department of Veterans Affairs: Building a Foundation for Success.

The Department of Veterans Affairs (VA) has made significant progress in treating hepatitis C virus, experiencing more than a 75% reduction in veterans remaining to be treated since the availability of oral direct-acting antivirals. Hepatitis C Innovation Teams use lean process improvement and system redesign, resulting in practice models that address gaps in care. The key to success is creative improvements in veteran access to providers, including expanded use of nonphysician providers, video telehealth, and electronic technologies. Population health management tools monitor and identify trends in care, helping the VA tailor care and address barriers.

Forming and activating an internal facilitation group for successful implementation: A qualitative study.

BACKGROUND: This study focuses on an implementation facilitation strategy to improve the delivery of anticoagulation care within pharmacy-run clinics across 8 Veterans Health Administration (VA) medical centers. Other studies have explored various models of implementation facilitation, including external facilitation (EF), internal facilitation (IF), and blended facilitation (BF) combining both approaches. This study focuses on the use of an internal facilitation team of anticoagulation coordinators representing 8 VA anticoagulation clinics to enhance the implementation process. This study examines how the team became instrumental in the successful implementation of evidence-based practice change. METHODS: Semi-structured interviews were conducted annually over 4 years with representatives from each site, the internal facilitators (site champions), at 8 VA hospitals (47 interviews). Additionally, five external facilitators, experts in quality improvement and anticoagulation care who guided the implementation, were interviewed. Analysis drew on a deductive approach based on the Promoting Action on Research Implementation in Health Services (PARIHS) model and emergent thematic analysis to identify factors related to effectiveness of the internal facilitation team. RESULTS: Key findings are that the following factors enhanced successful uptake of the anticoagulation initiative: 1) Regular participation by the site champion in the internal facilitation team; 2) Champion strongly committed to being an agent of change; and 3) Champion received greater support from their supervisors. The first and second factors are interrelated, as internal facilitators who actively and regularly participated in the internal facilitation team often became truly committed to the improvement project. Both factors relate to the third, as supervisor support not only facilitated changes in practice, but also facilitated regular team attendance and stronger participation. CONCLUSIONS: Our study adds to implementation science by detailing how internal facilitators learn their skills over time, and how a group of internal facilitators can help each other succeed. These findings can guide those who wish to incorporate internal facilitation teams as an implementation strategy, and demonstrate how sites can build capacity for implementation efforts. SYNOPSIS: This study focuses on an implementation facilitation strategy to improve the delivery of anticoagulation care within pharmacy-run clinics across 8 Veterans Health Administration medical centers. Internal facilitators (IFs) guided by and supported by an external facilitators (EF), successfully implemented the clinical innovation. This study examines how the IF group became instrumental in the successful implementation of evidence-based practice change.

Knowing the patient: A qualitative study on care-taking and the clinical pharmacist-patient relationship.

BACKGROUND: Previous studies have found clinical pharmacists (CPs) and clinical pharmacy specialists (CPSs) in direct patient care have positive effects across various patient outcomes. However, there are also other kinds of care-taking occurring in pharmacy-run clinic appointments that produce value for patients. OBJECTIVE: To identify and characterize how CPs/CPSs in direct care clinics develop and practice care-taking behaviors which advance the pharmacist-patient relationship. METHODS: Semi-structured CP/CPS interviews were conducted once per year for two years (46 year 1, 50 year 2) along with direct observations of clinical pharmacy work as part of an anticoagulation improvement intervention. Participants were from Veterans Health Administration (VHA) medical centers and VHA community-based outpatient clinics in the Northeastern U.S. Interviews were transcribed verbatim and thematically analyzed using NVIVO 10 software. RESULTS: It was found that CPs/CPSs practice "knowing the patient" in ways related to, but distinct from this practice in the nursing literature. For CPs/CPSs, knowing the patient occurred over time, and it produced familiarity and trust between CPs/CPs and patients. A reciprocal relationship developed in which patients came to rely on CP/CPSs for other types of assistance. Patterns of knowing the patient and being known by the patient manifested in three distinct ways: 1) identifying the patient's unmet needs, 2) explaining other medications, and 3) helping the patient navigate the system. CONCLUSION: This research identifies an action, knowing the patient, whereby CPs use their knowledge of the patient to deliver individualized care. This study contributes to the developing literature on pharmacist-patient relationships and pharmacist-patient communication.

High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure.

OBJECTIVES: The study examined the activations in the pulmonary veins (PVs) and the vein of Marshall (VOM) during atrial fibrillation (AF) in dogs with congestive heart failure (CHF). BACKGROUND: The patterns of activation within the PVs and the VOM during AF in CHF are unclear. METHODS: We induced CHF in nine dogs by rapid ventricular pacing. The patterns of activation during induced AF were studied one week after ceasing ventricular pacing. RESULTS: The duration of induced AF averaged 80.7 +/- 177.3 s. The termination of low-amplitude fractionated activity in the PVs preceded the termination of AF in 25 of 29 episodes. High-density mapping (1-mm resolution) showed that the PV was activated by a focal wave front independent of left atrial (LA) activation in 22 AF episodes. Frequent intra-PV conduction blocks and multiple wave fronts in the PVs were recorded during 10 AF episodes. Focal activations were observed within the VOM in 4 of 12 episodes of AF. Three atrial tachycardia (AT) episodes originated from a focus within a PV. Histological studies showed extensive fibrosis in the PVs and in the atria. The PVs in five normal dogs did not have focal or fractionated activity during induced AF. CONCLUSIONS: Atrial fibrillation in canine CHF is associated with independent focal activations in the PVs and the VOM, and with complex wave fronts within the PVs. The PVs may also serve as the origin of AT. These findings suggest that electrical and anatomical remodeling of the PVs and the VOM are important in the maintenance of AF and AT in dogs with CHF.

Distribution of cardiac nerves in patients with diabetes mellitus: an immunohistochemical postmortem study of human hearts.

BACKGROUND: Autonomic neuropathy and functional cardiac denervation are complications of diabetes mellitus (DM). It is unknown if DM patients show histopathologic evidence of cardiac denervation. METHODS AND RESULTS: Nine sites were sampled at fixed distances from the atrioventricular valves from 27 postmortem hearts. Sections were stained with antibodies to S100 protein and to neurofilament (NF). Samples were visualized by light microscopy using the avidin-biotin peroxidase technique. The amount of cardiac nerves was graded blindly using semiquantitative methods according to the following criteria: Grade 0=presence of nerves in the epicardium only; Grade 1=strictly perivascular nerves; Grade 2=Grade 1 and nerve sprouts between myocardial cells sporadically; Grade 3=Grade 2 and nerve sprouts throughout the myocardium and endocardium. Specimens were divided into four groups. Control group consisted of patients with neither myocardial infarction (MI) nor DM. Experimental groups consisted of MI (n=7), MI with DM (n=6), and DM without MI (n=8). Average age of all patients was 57.3+/-15.7 years. No age differences existed among groups. Heterogeneous nerve distribution existed in all groups. S100-positive nerve density for control, MI, DM and MI, and DM without MI are 1.95+/-0.40, 1.66+/-0.54, 1.54+/-0.37, and 1.81+/-0.14, respectively (P=ns). NF-positive nerve density in the same groups were 1.10+/-0.18, 1.31+/-0.24, 1.13+/-0.12, and 1.19+/-0.42, respectively (P=ns). No differences in nerve densities between anterior and inferoposterior sections of the left ventricle existed. CONCLUSION: In postmortem human hearts, cardiac nerve distribution was heterogeneous among normal, MI, and DM patients. No evidence of cardiac denervation in patients with DM was demonstrated.

ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

The Hypoxia-inducible Factor (HIF) family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs) are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs) in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM) composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs) and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2) signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

Hypoxia-inducible factor (HIF) and HIF-stabilizing agents in neonatal care.

Oxygen is essential for multicellular existence. Its reduction to water by the mitochondrial electron transport chain forms the cornerstone of aerobic metabolism. Conditions in which oxygen is limiting for electron transport result in bioenergetic collapse in metazoans. However, compared with postnatal existence, all of mammalian development occurs in a hypoxic environment in utero. Not just an epiphenomenon, this 'physiological hypoxia' is required for the activation of a transcriptional response mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators that coordinates the expression of hundreds of genes, many with developmentally critical functions. Oxygen tension, therefore, is a morphogen. Understanding the physiological significance of hypoxia responses during human development and the role of the HIF family of transcriptional regulators will have important consequences for the care of preterm neonates. Defining clinical care guidelines for the proper oxygenation of critically ill neonates that take account of these observations is therefore of paramount importance. The pharmacological stabilization of HIF family members may therefore have clinical utility in premature infants in whom this important morphogen has been inactivated by exposure to supraphysiological oxygen levels.

Thoracic vein ablation terminates chronic atrial fibrillation in dogs.

The thoracic vein hypothesis of chronic atrial fibrillation (AF) posits that rapid, repetitive activations from muscle sleeves within thoracic veins underlie the mechanism of sustained AF. If this is so, thoracic vein ablation should terminate sustained AF and prevent its reinduction. Six female mongrel dogs underwent chronic pulmonary vein (PV) pacing at 20 Hz to induce sustained (>48 h) AF. Bipolar electrodes were used to record from the atria and thoracic veins, including the vein of Marshall, four PVs, and the superior vena cava. Radio frequency (RF) application was applied around the PVs and superior vena cava and along the vein of Marshall until electrical activity was eliminated. Computerized mapping (1,792 electrodes, 1 mm resolution) was also performed. Sustained AF was induced in 30.6 +/- 6.5 days, and ablation was done 17.3 +/- 8.5 days afterward. Before ablation, the PVs had shorter activation cycle lengths than the atria, and rapid, repetitive activations were observed in the PVs. All dogs converted to sinus rhythm during (n = 4 dogs) or within 90 min of completion of RF ablation. Rapid atrial pacing afterward induced only nonsustained (<60 s) AF in all dogs. Average AF cycle lengths after reinduction were significantly (P = 0.01) longer (183 +/- 31.5 ms) than baseline (106 +/- 16.2 ms). There were no activation cycle length gradients after RF application. We conclude that thoracic vein ablation converts canine sustained AF into sinus rhythm and prevents the reinduction of sustained AF. These findings suggest that thoracic veins are important in the maintenance of AF in dogs.

Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation.

Repetitive rapid activities are present in the pulmonary veins (PVs) in dogs with pacing-induced sustained atrial fibrillation (AF). The mechanisms are unclear. We induced sustained (>48 h) AF by rapidly pacing the left atrium (LA) in six dogs. High-density computerized mapping was done in the PVs and atria. Results show repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation originated from the middle of the PV and then propagated to the LA and distal PV with conduction blocks. The right atrium (RA) was usually activated by a single large wavefront. Mean AF cycle length in the PVs (left superior, 82 +/- 6 ms; left inferior, 83 +/- 6 ms; right inferior, 83 +/- 4 ms) and LA posterior wall (87 +/- 5 ms) were significantly (P < 0.05) shorter than those in the LA anterior wall (92 +/- 4 ms) and RA (107 +/- 5 ms). PVs in normal dogs did not have focal activations during induced AF. No reentrant wavefronts were demonstrated in the PVs. We conclude that nonreentrant focal activations are present in the PVs in a canine model of pacing-induced sustained AF.