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"Yao, Ren Jie"
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Sensitivity, specificity, positive and negative predictive values of identifying atrial fibrillation using administrative data: a systematic review and meta-analysis
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.
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.
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.
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.
Journal Article
Use of a standardized asthma severity score to determine emergency department disposition for paediatric asthma: A cohort study
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.
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).
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.
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.
Journal Article
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.
Journal Article
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 1835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) International Classification of Diseases-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 two-fold depending solely on the methodological approach (6.5–15.0%). All-cause admission rates exhibited similar variation (18.8–29.9%). The highest rates included all consecutive index admissions (HF 11.1–15.0%, all-cause 24.0–29.9%), and the 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 with blanking the 30-day 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 two-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.
Graphical Abstract
Graphical Abstract
Journal Article
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.
Journal Article
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 l) 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. Keywords: Asthma; Clinical decision tool; Disposition from emergency.
Journal Article
Complications Following Radiofrequency Ablation of Benign Thyroid Nodules： A Systematic Review
Objective： This systematic review examined whether radiofrequency ablation （RFA） is a sate treatment modality for benign thyroid nodules （BTNs）. Data Sources： PubMed, Embase, and the Cochrane Library database were searched for articles that （a） targeted human beings and （b） had a study population with BTNs that were confirmed by fine-needle aspiration cytology and/or core needle biopsy. Study Selection： Thirty-two studies relating to 3409 patients were included in this systematic review. Results： Based on literatures, no deaths were associated with the procedure, serious complications were rare, and RFA appears to be a sale and well-tolerated treatment modality. However, a broad spectrum of complications offers insights into some undesirable complications, such as track needle seeding and Hornet syndrome. Conclusions： RFA appears to be a safe and well-tolerated treatment modality for BTNs. More research is needed to characterize the complications of RFA for thyroid nodules.
Journal Article
Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active （S）-Pregabalin and （R）-Baclofen
Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access （S）-Pregabalin and （R）-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles （1a） or 3-（4＇-chlorophenyl）glutaronitriles （1b） as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of la and lb to form optically active 3-（cyanomethyl）-5-methylhexanoic acid （2a） and 3-（4＇-chlorophenyl）-4-cyanobutanoic acid （2b） with high enantiomeric excesse （ee）, respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated （R）-2b whereas BjNIT6402 and HsN1T produced the opposite （S）-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substitueut of the substrates also exerted great effect on the enzyme activity and stereoselectivity. （S）-2a and （S）-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of （S）-2a and （S）-2b, followed by the acidic hydrolysis, afforded （S）-Pregabalin and （R）-Baclofen. This offers a new platform methodology for the synthesis of optically active β-substituted T-amino acids of pharmaceutical importance.
Journal Article
Sintering flue gas desulfurization with different carbon materials modified by microwave irradiation
Modification of metallurgical coke, biomass char and semi-coke was carried out using a microwave device with power of 450–850 W and irradiation time of 6–12 min. The desulfurization rates of three carbon materials before and after modification were tested. The effects of microwave power and irradiation time on the pore texture and surface chemical characteristics of the three carbon materials were examined by SEM, BET and Fourier transform infrared spectroscopy (FTIR). The results showed that the specific surface area, total pore volume and pore diameter of biomass char and semi-coke after irradiation decreased slightly. Noteworthily, the pore diameter turned small and the acidic functional groups on their surface decomposed, thereby the basicity of carbon surface increased by microwave modification. The optimal promotion of desulfurization rate of three carbon materials was semi-coke irradiated at 850 W for 9 min and the sulfur dioxide adsorption rate was up to 45%.
Journal Article