Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.

BACKGROUND: Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates. METHODS: Readmission rates were examined in 1,835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) ICD-10 codes (broad vs narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30-days), (4) follow-up period start (discharge date vs day following discharge), and (5) annual reference-period (calendar vs fiscal). The impact of different factors was assessed using linear-regression. RESULTS: The calculated 30-day readmission rate for HF varied more than 2-fold depending solely on the methodological approach (6.5% to 15.0%). All-cause admission rates exhibited similar variation (18.8% to 29.9%). The highest rates included all consecutive index admissions (HF 11.1-15.0%, all-cause 24.0-29.9%), and lowest only one index admission per patient per year (HF 6.5-11.3%, all-cause 18.8-22.7%). When including multiple index admissions and compared to blanking the 30-days post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (p<0.001). CONCLUSION: Calculated 30-day readmission rates varied more than 2-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.

Variability in Nonvitamin K Oral Anticoagulant Dose Eligibility and Adjustment According to Renal Formulae and Clinical Outcomes in Patients With Atrial Fibrillation With and Without Chronic Kidney Disease: Insights From ORBIT-AF II.

Background Nonvitamin K oral anticoagulants require dose adjustment based on kidney function.The most common estimate of kidney function employed in clinical practice is estimated glomerular filtration rate (eGFR); however, product monographs recommend the use of the Cockcroft-Gault estimated creatinine clearance (eCrCl) for dose adjustment. Methods and Results The authors included patients enrolled in the ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation AF II) trial. Dosing was considered inappropriate when use of eGFR resulted in a lower (undertreatment) or higher (overtreatment) dose than that recommended by the eCrCl. The primary outcome of major adverse cardiovascular and neurological events was a composite of cardiovascular death, stroke or systemic embolism, new-onset heart failure, and myocardial infarction. Among 8727 in the overall cohort, agreement between eCrCl and eGFR was observed in 93.5% to 93.8% of patients. Among 2184 patients with chronic kidney disease (CKD), the agreement between eCrCl and eGFR was 79.9% to 80.7%. Dosing misclassification was more frequent in the CKD population (41.9% of rivaroxaban users, 5.7% of dabigatran users, and 4.6% apixaban users). At 1 year, undertreated patients in the CKD group had significantly greater major adverse cardiovascular and neurological events (adjusted hazard ratio, 2.93 [95% CI, 1.08-7.92]) compared with the group with appropriate nonvitamin K oral anticoagulants dosing (P=0.03). Conclusions The prevalence of misclassification of nonvitamin K oral anticoagulants dosing was high when using eGFR, particularly among patients with CKD. Among patients with CKD, potential undertreatment due to inappropriate and off-label renal formulae may result in worse clinical outcomes. These findings highlight the importance of using eCrCl, and not eGFR, for dose adjustment in all patients with AF receiving nonvitamin K oral anticoagulants.

Efficacy of microcatheter-assisted trabeculotomy on secondary glaucoma after congenital cataract surgery.

AIM: To evaluate efficacy of microcatheter-assisted trabeculotomy (MAT) in eyes with secondary glaucoma after congenital cataract surgery and explore its correlation with the different degree of trabeculotomy. METHODS: A retrospective analysis was conducted on patients who underwent the said procedure between September 2019 and September 2020. The patients were classified into two groups according to the degree of trabeculotomy (group 1: ≤240-degree; group 2: 240-360-degree). The intraocular pressure (IOP) and anti-glaucoma drugs before and after operation was collected during the 12-month follow-up. RESULTS: Totally 27 eyes of 25 patients were included: 11 (40.7%) eyes in group 1 and 16 (59.3%) eyes in group 2. The mean IOP of all patients was 34.67±9.18 mm Hg preoperatively and 8.74±4.32, 9.95±5.65, 14.39±5.30, 16.02±4.37, 15.82±3.28, and 16.19±3.56 mm Hg 1d, 1wk, 1, 3, 6, and 12mo after surgery, respectively. In all patients, there were significant differences in IOP at each time point (F=65.614, P<0.01). In each group, IOP after surgery was lower than that before surgery (all P<0.01), but there was no difference in the rate of IOP reduction between the two groups (P=0.246). Furthermore, the amount of anti-glaucoma medications reduced to 0.30±0.67 (0-2) at 12mo from 2.63±0.49 (2-3) preoperatively (P<0.01), and there was no difference between the two groups (P>0.05). At the end of follow-up, the partial success rate was 81.8% in group 1 vs 93.75% in group 2 (P=0.549). Various amount of intraoperative and postoperative hyphema occurred in all eyes, which spontaneously absorbed or cleaned through paracentesis and irrigation. No other serious complications was observed. CONCLUSION: MAT can effectively reduce IOP in patients with secondary glaucoma after congenital cataract surgery with a high success rate and safety. And it can be used as the first choice for the treatment of secondary glaucoma after surgery for congenital cataracts.

Aging Impairs the Cellular Interplay between Myeloid Cells and Mesenchymal Cells during Skin Healing in Mice.

Impaired wound healing is a major issue in the elderly population and is associated with substantial health and economic burden, which is exponentially increasing with the growing aging population. While the underlying pathobiology of disturbed skin healing by aging is linked to several genetic and epigenetic factors, little is known about the cell-cell interaction during the wound healing process in aged individuals, particularly the mesenchymal stem cell (MSCs)-macrophages axis. In this study, by using a thermal injury animal model in which we compared the wound healing process of adult and young mice, we found that the insufficient pool of MSCs in adult animals are deficient in migrating to the wound bed and instead are restricted to the wound edge. We identified a deficiency of a CD90-positive MSC subpopulation in the wounds of adult animals, which is positively correlated with the number of F4/80+ macrophages. In vitro, we found that CD90+ cells preferentially adhere to the myeloid cells forming doublet cells. Thus, our findings highlight that in adult mice subjected to a thermal injury, impaired wound healing is likely mediated by a disturbed cellular interplay between myeloid cells and mesenchymal cells.

Anticoagulation management of postoperative atrial fibrillation after cardiac surgery: A systematic review.

BACKGROUND: Postoperative atrial fibrillation (POAF) often complicates cardiac surgery and is associated with increased mortality and risk of thromboembolism. However, the optimal oral anticoagulation (OAC) strategy is uncertain. We performed a systematic review to examine the OAC practice patterns and efficacy in these circumstances. METHODS: MEDLINE and EMBASE were searched from 2000 to 2019 using the search terms cardiac surgical procedures, cardiac surgery, postoperative complications, atrial fibrillation, atrial flutter, and terms for anticoagulants. Collected data included anticoagulation patterns (time of initiation, type, and duration) and outcomes (stroke, bleeding, and mortality). RESULTS: From 763 records, 4 prospective and 13 retrospective studies were included totaling 44,908 patients with 8929 (19.9%) who developed POAF. Anticoagulation rates ranged from 4% to 43% (mean 21% overall). Sixteen studies used warfarin, 3 nonvitamin K OAC (NOAC), and 2 both. Four studies reported the use of bridging unfractionated or low-molecular-weight heparin. Concomitant antiplatelet therapy was reported in half the studies, ranging from 80% to 99%. OAC use was associated with lower risk of thromboembolic events in two retrospective studies (including a national Danish cohort with 2108 patients with POAF). Patients discharged on warfarin experienced reduced mortality in a large, single center, retrospective analysis, but no association was observed in the Danish cohort. CONCLUSION: There is wide practice variation in the uptake, timing of initiation, duration, and choice of OAC for POAF following cardiac surgery. The evidence is largely retrospective and insufficient to assess the efficacy of different OAC strategies. Further studies are warranted to guide clinical practice.

Management strategies and clinical outcomes in breast cancer patients who develop left ventricular dysfunction during trastuzumab therapy.

BACKGROUND: Trastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). We assessed management patterns of trastuzumab-induced cardiotoxicity (TIC) in a contemporary real-world setting. METHODS: We reviewed charts of all breast cancer patients who received adjuvant trastuzumab in British Columbia between January 2010 and December 2013, spanning the opening of a cardio-oncology clinic. LV dysfunction (LVD) was classified as minimal (LVEF nadir 45-49%), mild (40-44%) or moderate-severe (< 40%). Charts were reviewed for baseline characteristics, management strategies, and outcomes. Multivariable analysis was performed to identify patient characteristics associated with trastuzumab completion and cardiology referral. RESULTS: Of 967 patients receiving trastuzumab, 171 (17.7%) developed LVD, including 114 patients (11.8%) with LVEF declines of ≥10 to < 50%. Proportions of patients receiving cardiology referrals and LVETx increased and wait times to consultation decreased after a dedicated cardio-oncology clinic opened. LVETx was used more frequently in patients with moderate-severe LVD compared to minimal or mild LVD. Factors associated with completion of trastuzumab included mastectomy (OR 5.1, 95% CI 1.1-23.0) and proximity to quaternary care centre (OR 7.7, 95% CI 2.2-26.2). Moderate-severe LVD was associated with a lower probability of completing trastuzumab (OR 0.07 vs. minimal LVD, 95% CI 0.01-0.74). Factors associated with cardiology referral included heart failure symptoms (OR 8.0, 95% CI 1.5-42.9), proximity to quaternary care centre (OR 6.8, 95% CI 1.3-34.2), later year of cancer diagnosis (OR 2.4 per year, 95% CI 1.4-4.3), node-positive disease (OR 0.18, 95% CI 0.06-0.56), mastectomy (OR 0.05, 95% CI 0.01-0.52), and minimal LVD (OR 0.14, 95% CI 0.05-0.46). LVEF recovered to > 50% in 90.7% of patients. CONCLUSIONS: Management strategies in patients with TIC are associated with cancer characteristics and severity of cardiotoxicity. Access to dedicated cardio-oncology clinics may facilitate optimal care of this complex patient population.

Impact of Female Sex on Clinical Presentation and Ablation Outcomes in the CIRCA-DOSE Study.

OBJECTIVES: This study sought to evaluate sex-specific differences in atrial fibrillation (AF) presentation and catheter ablation outcomes in the prospective, multicenter, randomized CIRCA-DOSE (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration) study. BACKGROUND: Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology, pathophysiology, presentation, and natural history of AF. Unfortunately, there are major gaps in our understanding of the pathophysiological basis for the observed sex-specific differences and their implications on therapy and prognosis. METHODS: This study examined sex-specific differences in AF presentation, symptom severity and health-related quality of life, symptomatic and asymptomatic arrhythmia recurrence, AF burden, and health care utilization. RESULTS: Freedom from any atrial tachyarrhythmia and symptomatic atrial tachyarrhythmia were similar between male (hazard ratio: 1.18; 95% confidence interval: 0.85 to 1.64; p = 0.39) and female patients (hazard ratio: 1.00; 95% confidence interval: 0.62 to 1.59; p = 0.92). Post-ablation, the median AF burden (percentage time in AF) was 0.00% (interquartile range: 0.00% to 0.16%) in male patients and 0.00% (interquartile range: 0.00% to 0.17%) in female patients, with no difference observed between the sexes (p = 0.30). Periprocedural complications occurred twice as frequently in female patients (3.5% vs. 7.0%; p = 0.18). In comparison to male patients, female patients reported a significantly worse symptom score and quality of life at baseline and all follow-up intervals, but they derived similar magnitude of improvement post-ablation. There was no difference between male and female patients with respect to emergency department visits, hospitalization, cardioversion, or repeat ablation. CONCLUSIONS: When compared with male patients, female patients have significantly worse symptom scores and quality of life at baseline. Despite this, female patients with symptomatic paroxysmal AF derive similar benefit in freedom from recurrent arrhythmia and similar improvements in quality of life following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration [CIRCA-DOSE]; NCT01913522).

Use of a standardized asthma severity score to determine emergency department disposition for paediatric asthma: A cohort study.

BACKGROUND: We recently introduced a clinical practice pathway for the management of asthma that uses the Pediatric Respiratory Assessment Measure (PRAM) to guide emergency department (ED) treatment and disposition. The pathway recommends discharge for patients who achieve improvement to PRAM <4 at 1 hour after the last bronchodilator. We evaluated practice variation and patient outcomes associated with PRAM-directed disposition recommendations. METHODS: We conducted a retrospective cohort study of children aged 2 to 17 years treated for moderate asthma (PRAM score 4-7) using our asthma clinical pathway. We measured 1) the proportion of children discharged per pathway criteria who returned to our ED within 24 hours and 2) the proportion of children observed beyond the pathway discharge criteria who deteriorated (PRAM ≥4). RESULTS: We analyzed 385 patient records from September 2013 to February 2015. Among 145 (37.7%) patients discharged per pathway criteria, 4 (4/145; 2.8%) returned within 24 hours. The remaining 240 (62.2%) were observed beyond the pathway discharge criteria; 76/240 (31.7%) had a subsequent deterioration (PRAM score ≥ 4) and 25/240 (10.4%) were hospitalized. Of those who deteriorated, 46/76 (60.5%) worsened within the first additional hour of observation. CONCLUSION: We observed significant deviation from our PRAM-directed pathway discharge criteria and that a significant proportion of observed patients experienced clinical deterioration beyond the first hour of observation. We recommend observing children with moderate asthma for 2 or 3 hours from last bronchodilator therapy if PRAM < 4 is maintained, to capture the majority (97.7% or 99.7%) of patients who require further intervention and hospitalization.

Sensitivity, specificity, positive and negative predictive values of identifying atrial fibrillation using administrative data: a systematic review and meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) is the commonest arrhythmia and a major cause of stroke and health care utilization. Researchers and administrators use electronic health data to assess disease burden, quality and variance in care, value of interventions and prognosis. We performed a systematic review and meta-analysis to assess the validity of AF case definitions in administrative databases. METHODS: Medline was searched from 2000 to 2018. Extracted information included sensitivity, specificity, positive and negative predictive values (PPV and NPV) for various AF case definitions. Estimates were pooled using random-effects models due to significant heterogeneity between studies. RESULTS: We identified 24 studies, including 21 from North America or Scandinavia. Hospital, ambulatory and mixed data sources were assessed in 10, 4 and 10 studies, respectively. Nine different AF case definitions were evaluated, most based on ICD-9 or 10 codes. Twenty-two studies assessed case definitions in patients diagnosed with AF and thus could generate PPV alone. Half the studies sampled unrestricted populations including a mix of those with and without AF to assess sensitivity. Only 13 studies included ECG confirmation as a gold standard. The pooled random effects estimates were: sensitivity 80% (95% CI 72-86%); specificity 98% (96-99%); PPV 88% (82-94%); NPV 97% (94-99%). Only 3 studies reported all accuracy parameters and included rhythm monitoring in the gold standard definition. CONCLUSION: Relatively few studies examined sensitivity, and fewer still included rhythm monitoring in the gold standard comparison. Administrative data may fail to identify a significant proportion of patients with AF. This, in turn, may bias estimates of quality of care and prognosis.

Clinical effectiveness of a systematic "pill-in-the-pocket" approach for the management of paroxysmal atrial fibrillation.

BACKGROUND: For patients with symptomatic, sustained atrial fibrillation (AF), a "pill-in-the-pocket" antiarrhythmic drug (PIP-AAD) strategy has been proposed to reduce emergency department (ED) use. OBJECTIVE: To assess the clinical utility of a protocolled PIP-AAD approach within contemporary practice. METHODS: Consecutive patients who hemodynamically tolerated symptomatic, sustained AF were prospectively managed with the PIP-AAD strategy. All patients were given an atrioventricular nodal blocker 30 minutes prior to a single oral dose of a class Ic antiarrhythmic drug. If the initial PIP-AAD in the ED was efficacious and tolerated, PIP-AADs were given out of hospital for subsequent sustained AF episodes. Usage and complications were systematically recorded. RESULTS: During a median follow-up period of 565 days, 43 of 80 patients presented to the ED for initial PIP-AAD. Sinus rhythm was restored without complication in 30 of 43 patients. The reasons for initial PIP-AAD failure were inefficacy (6 patients), significant hypotension (4 patients), conversion to flutter necessitating cardioversion (2 patients), and syncopal conversion pause (1 patient). For the 30 patients with successful initial PIP-AAD, 159 out-of-hospital PIP-AAD treatments occurred (mean 5.3 ± SD 1.3 per patient). Compared with ED visits in the period prior to PIP-AAD initiation, there was a significant reduction in visits (2.6 ± 3.0 vs. 0.4±0.9 ED visits per patient, P < .001) and the need for cardioversion (2.3 ± 3.1 vs. 0.0 ± 0.2 treatments per patient, P < .001). Adverse events associated with out-of-hospital PIP-AAD include presyncope (3 of 30 patients), syncope necessitating pacemaker implantation (1 patient), and conversion to flutter (1 patient). CONCLUSION: Out-of-hospital PIP-AAD can be an effective for highly selected patients; however, the rates of treatment failure and adverse events are clinically relevant, which limits the widespread application of a PIP-AAD approach.

HDAC and Proteasome Inhibitors Synergize to Activate Pro-Apoptotic Factors in Synovial Sarcoma.

Conventional cytotoxic therapies for synovial sarcoma provide limited benefit, and no drugs specifically targeting its driving SS18-SSX fusion oncoprotein are currently available. Patients remain at high risk for early and late metastasis. A high-throughput drug screen consisting of over 900 tool compounds and epigenetic modifiers, representing over 100 drug classes, was undertaken in a panel of synovial sarcoma cell lines to uncover novel sensitizing agents and targetable pathways. Top scoring drug categories were found to be HDAC inhibitors and proteasomal targeting agents. We find that the HDAC inhibitor quisinostat disrupts the SS18-SSX driving protein complex, thereby reestablishing expression of EGR1 and CDKN2A tumor suppressors. In combination with proteasome inhibition, HDAC inhibitors synergize to decrease cell viability and elicit apoptosis. Quisinostat inhibits aggresome formation in response to proteasome inhibition, and combination treatment leads to elevated endoplasmic reticulum stress, activation of pro-apoptotic effector proteins BIM and BIK, phosphorylation of BCL-2, increased levels of reactive oxygen species, and suppression of tumor growth in a murine model of synovial sarcoma. This study identifies and provides mechanistic support for a particular susceptibility of synovial sarcoma to the combination of quisinostat and proteasome inhibition.

Optimising the Haemodynamics of Aortic Valve-in-valve Procedures.

Bioprosthetic surgical valves are increasingly implanted during cardiac surgery, instead of mechanical valves. These tissue valves are associated with limited durability and as a result transcatheter valve-in-valve procedures are performed to treat failed bioprostheses. A relatively common adverse event of aortic valve-in-valve procedures is residual stenosis. Larger surgical valve size, supra-annular transcatheter heart valve type, as well as higher transcatheter heart valve implantation depth, have all been shown to reduce the incidence of elevated post-procedural gradients. With greater understanding of technical considerations and surgical planning, valve-in-valve procedures could be more effective and eventually may become the standard of care for our increasingly ageing and comorbid population with failed surgical bioprostheses.