Predictors of Physician Compassion,Empathy, and Related Constructs: a Systematic Review

BackgroundCompassion in healthcare provides measurable benefits to patients, physicians, and healthcare systems. However, data regarding the factors that predict care (and a lack of care) are scattered. This study systematically reviews biomedical literature within the Transactional Model of Physician Compassion and synthesizes evidence regarding the predictors of physician empathy, compassion, and related constructs (ECRC).MethodsA systematic literature search was conducted in CENTRAL, MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, OvidJournals, ProQuest, Web of Science, and Scopus using search terms relating to ECRC and its predictors. Eligible studies included physicians as participants. Methodological quality was assessed based on the Cochrane Handbook, using ROBINS-I risk of bias tool for quantitative and CASP for qualitative studies. Confidence in findings was evaluated according to GRADE-CERQual approach.ResultsOne hundred fifty-two included studies (74,866 physicians) highlighted the diversity of influences on compassion in healthcare (54 unique predictors). Physician-related predictors (88%) were gender, experience, values, emotions and coping strategies, quality of life, and burnout. Environmental predictors (38%) were organizational structure, resources, culture, and clinical environment and processes. Patient-related predictors (24%) were communication ease, and physicians’ perceptions of patients’ motives; compassion was also less forthcoming with lower SES and minority patients. Evidence related to clinical predictors (15%) was scarce; high acuity presentations predicted greater ECRC.DiscussionThe growth of evidence in the recent years reflects ECRC’s ongoing importance. However, evidence remains scattered, concentrates on physicians’ factors that may not be amenable to interventions, lacks designs permitting causal commentary, and is limited by self-reported outcomes. Inconsistent findings in the direction of the predictors’ effects indicate the need to study the relationships among predictors to better understand the mechanisms of ECRCs. The current review can guide future research and interventions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07055-2.     

Toward a Learning Health Care System: A Systematic Review and Evidence-Based Conceptual Framework for Implementation of Clinical Analytics in a Digital Hospital

Objective  A learning health care system (LHS) uses routinely collected data to continuously monitor and improve health care outcomes. Little is reported on the challenges and methods used to implement the analytics underpinning an LHS. Our aim was to systematically review the literature for reports of real-time clinical analytics implementation in digital hospitals and to use these findings to synthesize a conceptual framework for LHS implementation. Methods  Embase, PubMed, and Web of Science databases were searched for clinical analytics derived from electronic health records in adult inpatient and emergency department settings between 2015 and 2021. Evidence was coded from the final study selection that related to (1) dashboard implementation challenges, (2) methods to overcome implementation challenges, and (3) dashboard assessment and impact. The evidences obtained, together with evidence extracted from relevant prior reviews, were mapped to an existing digital health transformation model to derive a conceptual framework for LHS analytics implementation. Results  A total of 238 candidate articles were reviewed and 14 met inclusion criteria. From the selected studies, we extracted 37 implementation challenges and 64 methods employed to overcome such challenges. We identified common approaches for evaluating the implementation of clinical dashboards. Six studies assessed clinical process outcomes and only four studies evaluated patient health outcomes. A conceptual framework for implementing the analytics of an LHS was developed. Conclusion  Health care organizations face diverse challenges when trying to implement real-time data analytics. These challenges have shifted over the past decade. While prior reviews identified fundamental information problems, such as data size and complexity, our review uncovered more postpilot challenges, such as supporting diverse users, workflows, and user-interface screens. Our review identified practical methods to overcome these challenges which have been incorporated into a conceptual framework. It is hoped this framework will support health care organizations deploying near-real-time clinical dashboards and progress toward an LHS.     

Multimodal Percutaneous Intervention for Critical Venous Occlusive Disease

Critical deep venous thrombosis and occlusion constitutes a small percentage of patients with venous disease, who exhibit severe symptomatology. This study examined the results of multimodal percutaneous therapy for the treatment of complex critical venous thrombotic and occlusive disease. Twenty-five patients presented with critical venous thromboses or occlusions (11 with debilitating unilateral lower extremity edema causing ambulatory impairment, 2 with debilitating bilateral lower extremity edema, 3 with phlegmasia cerulea dolens, 2 with venous claudication, 2 with superior vena cava (SVS) syndrome with respiratory compromise, 4 with debilitating upper extremity edema, and 1 with renal insufficiency). Therapeutic modalities including thrombolysis, mechanical thrombectomy, percutaneous venoplasty and stent placement, temporary inferior vena cava filtration, and ultrasound guidance were used in all cases in conjunction with long-term systemic anticoagulation. The venous access site was determined by the anatomic location of the lesion and included popliteal, femoral, brachial, and lesser saphenous. Patients were followed with clinical exam and duplex surveillance. Resolution of symptoms was achieved in 18 of 25 patients (72%) and partial resolution occurred in 4 of 25 (16%). Failure of treatment identified as both lack of clinical response and evidence of continued venous thrombosis occurred 3 of 25 patients (12%). Restoration of arterial pulses and limb salvage was achieved in the three patients with phlegmasia cerulea dolens and acute limb-threatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The mean length of follow-up was 11 ± 2.7 months. Complications included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment. The relief of pain and resolution of acutely life and limb-threatening conditions in this most severely symptomatic subset of patients represents the immediate goal of treatment.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.     

Aortic dissection with branch vessel occlusion: percutaneous treatment with fenestration and stenting

Aortic dissection involves a tear in the intimal and medial layers of the aortic wall. Early surgical treatment of this condition can be fraught with complications especially when the procedure to be performed involves treatment of renal and visceral vessels. Additionally, patients with this problem can have severe compromise of the flow to branches or the entire aortic distribution. Methods of endovascular therapy for these problems limit the surgical stress and often can be performed in less time than surgical revascularization might require. The use of endovascular stenting to improve vessel perfusion and fenestration of the dissection membrane to decrease pressure within the false lumen can be performed to relieve ischemic vascular beds and potentially decrease the risk of aneurysmal dilatation of the aorta. The increasing use of these techniques may allow stabilization of these patients before open repair of more proximal aortic dissection or a combination of therapy with endovascular stent grafting techniques.     

The endovascular management of visceral artery aneurysms and pseudoaneurysms

OBJECTIVE: Visceral artery aneurysms may be treated by aneurysm exclusion, excision, revascularization, and endovascular techniques. The purpose of this study was to review the outcomes of the management of visceral artery aneurysms with catheter-based techniques. METHODS: Between 1997 and 2005, 90 patients were identified with a diagnosis of visceral artery aneurysm. This was inclusive of aneurysmal disease of the celiac axis, superior mesenteric artery (SMA), inferior mesenteric artery, and their branches. Surveillance without intervention occurred in 23 patients, and 19 patients underwent open aneurysm repair (4 ruptures). The endovascular treatment of 48 consecutive patients (mean age 58, 60% men) with 20 visceral artery aneurysms (VAA) and 28 visceral artery pseudoaneurysms (VAPA) was the basis for this study. Electronic and hardcopy medical records were reviewed for demographic data and clinical variables. Original computed tomography (CT) scans and fluoroscopic imaging were evaluated. RESULTS: The endovascular treatment of visceral artery aneurysms was technically successful in 98% of 48 procedures, consisting of 3 celiac axis repairs, 2 left gastric arteries, 1 SMA, 12 hepatic arteries, 20 splenic arteries, 7 gastroduodenal arteries, 1 middle colic artery, and 2 pancreaticoduodenal arteries. Of these, 29 (60%) were performed for symptomatic disease (5 ruptured aneurysms). Procedures were performed in the endovascular suite under local anesthesia with conscious sedation (94%). The femoral artery was used as the preferential access site (90%). Coil embolization was used for aneurysm exclusion in 96%. N-butyl-2-cyanoacrylate (glue) was used selectively (19%) using a triaxial system with a 3F microcatheter for persistent flow or multiple branches. The 30-day mortality was 8.3% (n = 4). One patient died from recurrent gastrointestinal bleeding after gastroduodenal embolization, and the remaining died of unrelated causes. All perioperative deaths occurred in patients requiring urgent or emergent intervention in the setting of hemodynamic instability. No patients undergoing elective intervention died in the periprocedural period. Postprocedural imaging was performed after 77% of interventions at a mean of 16 months. Complete exclusion of flow within the aneurysm sac occurred in 97% interventions with follow-up imaging, but coil and glue artifact complicated CT evaluation. Postembolization syndrome developed in three patients (6%) after splenic artery embolization. There was no evidence of hepatic insufficiency or bowel ischemia after either hepatic or mesenteric artery aneurysm treatment. Three patients required secondary interventions for persistent flow (n = 1) and recurrent bleeding from previously embolized aneurysms (n = 2). CONCLUSION: Visceral artery aneurysms and pseudoaneurysms can be successfully treated with endovascular means with low periprocedural morbidity; however, the urgent repair of these lesions is still associated with elevated mortality rates. Aneurysm exclusion can be accomplished with coil embolization and the selective use of N-butyl-2-cyanoacrylate. Current catheter-based techniques extend our ability to exclude visceral artery aneurysms, but imaging artifact hampers postoperative CT surveillance.     

Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts.

The RII beta regulatory subunit of cAMP-dependent protein kinase (PKA) contains an autophosphorylation site and a nuclear location signal, KKRK. We approached the structure-function analysis of RII beta by using site-directed mutagenesis. Ser114 (the autophosphorylation site) of human RII beta was replaced with Ala (RII beta-P) or Arg264 of KKRK was replaced with Met (RII beta-K). ras-transformed NIH 3T3 (DT) cells were transfected with expression vectors for RII beta, RII beta-P, and RII beta-K, and the effects on PKA isozyme distribution and transformation properties were analyzed. DT cells contained PKA-I and PKA-II isozymes in a 1:2 ratio. Over-expression of wild-type or mutant RII beta resulted in an increase in PKA-II and the elimination of PKA-I. Only wild-type RII beta cells demonstrated inhibition of both anchorage-dependent and -independent growth and phenotypic change. The growth inhibitory effect of RII beta overexpression was not due to suppression of ras expression but was correlated with nuclear accumulation of RII beta. DT cells demonstrated growth inhibition and phenotypic change upon treatment with 8-Cl-cAMP. RII beta-P or RII beta-K cells failed to respond to 8-Cl-cAMP. These data suggest that autophosphorylation and nuclear location signal sequences are integral parts of the growth regulatory mechanism of RII beta.     

Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B

RNA splicing plays a fundamental role in human biology. Its relevance in cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B in primary leukemia cells derived from patients with chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD-895 and pladienolide-B induce an early pattern of mRNA intron retention – spliceosome modulation. This process was associated with apoptosis preferentially in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of these compounds was observed regardless of poor prognostic factors such as Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect of culture conditions that resemble the tumor microenvironment. In addition, the activity of these compounds was observed not only in vitro but also in vivo using the A20 lymphoma murine model. Overall, these findings give evidence for the first time that spliceosome modulation is a valid target in chronic lymphocytic leukemia and provide an additional rationale for the development of spliceosome modulators for cancer therapy.