An Intensive Intervention to Reduce Readmissions for Frequently Hospitalized Patients: the CHAMP Randomized Controlled Trial

BackgroundA small number of patients are disproportionally readmitted to hospitals. The Complex High Admission Management Program (CHAMP) was established as a multidisciplinary program to improve continuity of care and reduce readmissions for frequently hospitalized patients.ObjectiveTo compare hospital utilization metrics among patients enrolled in CHAMP and usual care.DesignPragmatic randomized controlled trial.ParticipantsInclusion criteria were as follows: 3 or more, 30-day inpatient readmissions in the previous year; or 2 inpatient readmissions plus either a referral or 3 observation admissions in previous 6 months.InterventionsPatients randomized to CHAMP were managed by an interdisciplinary team including social work, physicians, and pharmacists. The CHAMP team used comprehensive care planning and inpatient, outpatient, and community visits to address both medical and social needs. Control patients were randomized to usual care and contacted 18 months after initial identification if still eligible.Main MeasuresPrimary outcome was number of 30-day inpatient readmissions 180 days following enrollment. Secondary outcomes were number of hospital admissions, total hospital days, emergency department visits, and outpatient clinic visits 180 days after enrollment.Key ResultsThere were 75 patients enrolled in CHAMP, 76 in control. Groups were similar in demographic characteristics and baseline readmissions. At 180 days following enrollment, CHAMP patients had more inpatient 30-day readmissions [CHAMP incidence rate 1.3 (95% CI 0.9–1.8) vs. control 0.8 (95% CI 0.5–1.1), p=0.04], though both groups had fewer readmissions compared to 180 days prior to enrollment. We found no differences in secondary outcomes.ConclusionsFrequently hospitalized patients experienced reductions in utilization over time. Though most outcomes showed no difference, CHAMP was associated with higher readmissions compared to a control group, possibly due to consolidation of care at a single hospital. Future research should seek to identify subsets of patients with persistently high utilization for whom tailored interventions may be beneficial.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640KEY WORDS: care transitions, readmissions, care models, continuity of care, randomized controlled trial

A small number of patients account for a disproportionate number of hospital readmissions.¹ While medically diverse, many patients who are frequently hospitalized have behavioral or social needs that require holistic care models emphasizing more than medical care alone.² This population challenges a system of care that fragments hospital-based care and ambulatory care, creating systematic discontinuity for patients who may require longitudinal relationship-based care to meet their complex needs.³ In qualitative studies, patients who are frequently hospitalized report frustration with care fragmentation, causing them to perceive a lack of continuity and a loss of trust with the medical system.⁴Innovative care models have sought to reduce readmissions through redesigning care delivery, improving care coordination, and connecting patients to existing resources.^5–8 A systematic review of interventions for frequently hospitalized patients found a heterogeneous group of care models.⁹ Importantly, the majority of studies were observational. Many patients experience a reduction in utilization after an initial period of frequent admissions,¹⁰ limiting the ability of observational studies to measure a specific program’s effect due to the natural decline in readmissions over time. A randomized trial of a “healthcare hotspotting” intervention for patients in Camden, NJ, reported no change in hospitalization rates compared to a control group.¹¹ Though this intervention was an intensive interdisciplinary effort that enrolled patients while still hospitalized, it focused primarily on connecting patients to existing outpatient resources. Other intensive outpatient-only interventions have failed to reduce healthcare utilization.¹² Interventions that focus on improving care across clinical settings (i.e., both inside and outside of the hospital) may have a different effect.We created the Complex High Admission Management Program (CHAMP) as a quality improvement initiative to improve inpatient and outpatient care and reduce inpatient readmissions of patients frequently admitted to our hospital. The CHAMP multidisciplinary team works to foster longitudinal relationships with patients who suffer from systematic discontinuity. A pilot pre-post analysis of CHAMP observed reductions in readmission;¹³ however, results may have been confounded by the aforementioned tendency for utilization to decline over time.¹⁰ In this study, we conducted a randomized trial of CHAMP compared with usual care to accurately assess the program’s effect on hospital readmissions.     

Cancer‐associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse‐strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage

Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal‐binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3′ end of the 5p miRNA strand of a pre‐mRNA hairpin. To investigate the effects of these cancer‐associated 'hotspot' mutations, we engineered mouse DICER1‐deficient ES cells to express wild‐type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal‐binding site mutations were compared to each other and to wild‐type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation‐carrying cells were distinct from both wild‐type and DICER1‐deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p‐derived miRNAs. We therefore conclude that cancer‐associated somatic hotspot mutations of DICER1, affecting any one of four metal‐binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The use of atrial pacing to induce atrial fibrillation and flutter

We studied the clinical and electrophysiological significance of induction of atrial fibrillation or atrial flutter by atrial electrical stimulation. Our atrial fibrillation/flutter induction protocol included incremental atrial pacing up to a rate of 200 beats/min, ramp up to 250 and 300 beats/min, and bursts up to 600 beats/min. The end point was sustained atrial fibrillation/flutter induction (30 sec). We performed a provocative study on 72 subjects previously divided into three groups: the first was the control group; the second comprised patients with spontaneous paroxysmal atrial fibrillation/flutter; the third comprised patients without spontaneous atrial fibrillation/flutter, but with pathologies assumed to put them at risk for atrial fibrillation/flutter. We were unable to induce sustained atrial fibrillation/flutter in the control group, but were able to induce these arrhythmias in 95% of the subjects with spontaneous atrial fibrillation/flutter. Thus the methods have a sensitivity of 95% and a specificity of 100%. We were also able to induce atrial fibrillation/flutter in 57% of patients at risk for atrial fibrillation/flutter, that is a lower incidence than patients with spontaneous episodes. When sustained atrial fibrillation/flutter could be induced, it was well tolerated and stopped spontaneously in less than 24 hours without treatment. The technique thus involves no risk and demonstrates that antiarrhythmic therapy is usually superfluous in interrupting induced atrial fibrillation/flutter.     

Coronary artery reconstruction for extensive coronary disease: 108 patients and two year follow-up

BACKGROUND: Surgical coronary artery reconstruction for diffuse coronary disease is described and assessed. METHODS: A long arteriotomy, internal thoracic artery graft, and exclusion of atheromatous plaques from the coronary lumen are the bases of the technique. One hundred eighteen reconstructions were performed in 108 patients with a mean age of 59 years. Stable angina was present in 62% of patients and unstable angina in 22%. Sixteen percent had had a recent myocardial infarction. The reconstructions involved 94 left anterior descending coronary arteries, 17 marginal, 5 diagonal, and 2 right coronary arteries. RESULTS: The perioperative mortality rate was 3.7% (4 patients). The rate of perioperative myocardial infarction was 6.3%. Mean follow-up was 29 months (standard deviation, 10 months). Two patients were lost to follow-up. Ninety patients were free from angina and cardiac-related events. Five patients sustained a myocardial infarction, 3 were in congestive heart failure, 3 had class II angina, and 1 died of stroke. Seventy-four of the surgical coronary artery reconstructions have been angiographically evaluated (29 months): 94.6% of the internal thoracic artery grafts were completely patent, and 70 of the reconstructions were patent without restenosis. String signs and occlusions were present in two internal thoracic arteries each. CONCLUSIONS: This technique allows revascularization of severely and diffusely diseased coronary arteries with encouraging results.     

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Synergistic inhibition of platelet activation by plasmin and prostaglandin I2

Endothelial cell prostacyclin (PGI2) inhibits platelet activation by raising platelet cyclic AMP. Previously, platelet activation was also shown to be blocked by plasmin formed by endothelium-derived tissue plasminogen activator (TPA). We have now studied interactions between PGI2 and plasmin in the control of platelet function. PGI2 and plasmin cause synergistic inhibition of thrombin- and ADP-induced aggregation of washed platelets. Inhibition by PGI2 is similarly potentiated by TPA added to platelet-rich plasma to generate plasmin. Thrombin-stimulated rise in platelet cytosolic Ca2+, measured by fura2 fluorescence, and thromboxane A2 formation, measured by radioimmunoassay (RIA), are likewise synergistically inhibited by PGI2 and plasmin. Plasmin neither increases nor potentiates PGI2-stimulated increases in platelet cyclic AMP. Thus, PGI2 and plasmin cause synergistic inhibition of platelet activation by both cyclic AMP-dependent and independent mechanisms. This interaction between two different endothelium-derived products may play an important role in localizing the hemostatic plug to a site of vascular injury by preventing further thrombin-mediated accrual of platelets.     

氯化四乙基铵及维拉帕米对家兔缺血心肌不应期的影响

实验比较了K⁺通道阻断剂氯化四乙基铵(TEA)及Ca²⁺通道阻断剂维拉帕米(verapamil,Ver)对家兔缺血性心室肌不应期(ERP)的影响。结果表明,阻断冠脉10min及30min后,缺血中心区(CIZ)和缺血边缘区(BIZ)心肌ERP比缺血前均明显缩短,而TEA和Ver均能延长急性缺血性心肌的ERP,可能对心肌缺血引起的心律失常有预防作用。     

Food consumption and cancer of the colon and rectum in north-eastern Italy.

The relation between dietary factors and the risk of colorectal cancer was investigated in a case-control study conducted in Pordenone province, North-eastern Italy, on 123 cases of colon cancer, 125 of rectal cancer and 699 controls admitted to hospital for acute, non-neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of bread (odds ratio, OR = 2.1 for colon and 2.2 for rectum for highest vs. lowest tertile), polenta (OR = 2.1 for colon, 1.9 for rectum), cheese (OR = 1.7 for colon, 1.8 for rectum) and eggs (2.5 for colon, 1.9 for rectum), whereas reduced ORs were observed in subjects reporting more frequent consumption of tomatoes (OR = 0.5 for colon and 0.4 for rectum). High consumption of margarine exerted a significant protection against cancer of the colon whereas high consumption of carrot spinach, whole-grain bread and pasta (favorably) and red meat (unfavorably) affected rectal cancer risk in particular. Thus the present study gives support for a protective effect associated with a fiber-rich or vegetable-rich diet, while it indicates that frequent consumption of refined starchy foods, eggs and fat-rich foods such as cheese and red meat is a risk factor for colo-rectal cancer.