Sex-based Differences in the Phenotypic Expression and Prognosis of Idiopathic Non-ischemic Cardiomyopathy: A Cardiovascular Magnetic Resonance Study.

AIMS: We sought to characterize sex-related differences in CMR-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia.A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; p-value<0.01 for all) versus males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (23% versus 36%; p-value<0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; p-value=0.003 and 0.005). There was no association of sex with the outcome. CONCLUSIONS: In a large contemporary cohort, NICM was uniquely expressed in females versus males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

Impact of myocardial perfusion and coronary calcium on medical management for coronary artery disease.

AIMS: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) remains one of the most widely used imaging modalities for the diagnosis and prognostication of coronary artery disease (CAD). Despite the extensive prognostic information provided by MPI, little is known about how this influences the prescription of medical therapy for CAD. We evaluated the relationship between MPI with computed tomography (CT) attenuation correction and prescription of acetylsalicylic acid (ASA) and statins. METHODS AND RESULTS: We performed a retrospective analysis of consecutive patients who underwent SPECT MPI at a single centre between 2015 and 2021. Myocardial perfusion abnormalities and coronary calcium burden were assessed, with attenuation correction imaging 77.8% of patients. Medication prescriptions before and within 180 days after the test were compared. Associations between abnormal perfusion and calcium burden with ASA and statin prescription were assessed using multivariable logistic regression. In total, 9908 patients were included, with a mean age 66.8 ± 11.7 years and 5337 (53.9%) males. The prescription of statins increased more in patients with abnormal perfusion (increase of 19.2 vs. 12.0%, P < 0.001). Similarly, the presence of extensive CAC led to a greater increase in statin prescription compared with no calcium (increase 12.1 vs. 7.8%, P < 0.001). In multivariable analyses, ischaemia and coronary artery calcium were independently associated with ASA and statin prescription. CONCLUSION: Abnormal MPI testing was associated with significant changes in medical therapy. Both calcium burden and perfusion abnormalities were associated with increased prescriptions of medical therapy for CAD.

Outcomes and Healthcare Utilization Among New Persistent Opioid Users and Nonopioid Users After Curative-intent Surgery for Cancer.

OBJECTIVE: The aim of the study was to compare the health outcomes and resource use of cancer patients who were new persistent opioid users with those who were not, after undergoing curative intent surgery for cancer. BACKGROUND: Little is known about long-term health outcomes (overdose, mortality) and resource utilization of new persistent opioid users among cancer patients undergoing curative-intent surgery. METHODS: This retrospective cohort study included all adults with a diagnosis of solid cancers who underwent curative-intent surgery during the study period (2011-2015) in Alberta, Canada and were opioid-naïve before surgery, with a follow-up period until December 31, 2019. The key exposure, "new persistent opioid user," was defined as a patient who was opioid-naive before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. The primary outcome was opioid overdose that occurred within 3 years of surgery. All-cause death, noncancer caused death, and department visit (yes vs. no), and hospitalization (yes vs. no) in the follow-up periods were also included as outcomes. RESULTS: In total, 19,219 patients underwent curative intent surgery with a median follow-up of 47 months, of whom 1530 (8.0%) were identified as postoperative new persistent opioid users. In total, 101 (0.5%) patients experienced opioid overdose within 3 years of surgery. Compared with nonopioid users, new persistent opioid users experienced a higher rate of opioid overdose (OR = 2.37, 95% CI: 1.44-3.9) within 3 years of surgery. New persistent opioid use was also associated with a greater likelihood of being hospitalized (OR = 2.03, 95% CI: 1.76-2.33) and visiting an emergency room (OR = 1.83, 95% CI: 1.62-2.06) in the first year after surgery, and a higher overall (HR = 1.28, 95% CI: 1.1-1.49) and noncancer caused mortality (HR = 1.33, 95% CI: 1.12-1.58), when compared with nonopioid users. CONCLUSION: Postoperative new persistent opioid use among cancer patients undergoing curative-intent surgery is associated with subsequent opioid overdose, worse survival, and more health resource utilization.

Performance of machine learning algorithms for surgical site infection case detection and prediction: A systematic review and meta-analysis.

Background: Medical researchers and clinicians have shown much interest in developing machine learning (ML) algorithms to detect/predict surgical site infections (SSIs). However, little is known about the overall performance of ML algorithms in predicting SSIs and how to improve the algorithm's robustness. We conducted a systematic review and meta-analysis to summarize the performance of ML algorithms in SSIs case detection and prediction and to describe the impact of using unstructured and textual data in the development of ML algorithms. Methods: MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science were searched from inception to March 25, 2021. Study characteristics and algorithm development information were extracted. Performance statistics (e.g., sensitivity, area under the receiver operating characteristic curve [AUC]) were pooled using a random effect model. Stratified analysis was applied to different study characteristic levels. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed. Results: Of 945 articles identified, 108 algorithms from 32 articles were included in this review. The overall pooled estimate of the SSI incidence rate was 3.67%, 95% CI: 3.58-3.76. Mixed-use of structured and textual data-based algorithms (pooled estimates of sensitivity 0.83, 95% CI: 0.78-0.87, specificity 0.92, 95% CI: 0.86-0.95, AUC 0.92, 95% CI: 0.89-0.94) outperformed algorithms solely based on structured data (sensitivity 0.56, 95% CI:0.43-0.69, specificity 0.95, 95% CI:0.91-0.97, AUC = 0.90, 95% CI: 0.87-0.92). Conclusions: ML algorithms developed with structured and textual data provided optimal performance. External validation of ML algorithms is needed to translate current knowledge into clinical practice.

Personalized prediction of incident hospitalization for cardiovascular disease in patients with hypertension using machine learning.

BACKGROUND: Prognostic information for patients with hypertension is largely based on population averages. The purpose of this study was to compare the performance of four machine learning approaches for personalized prediction of incident hospitalization for cardiovascular disease among newly diagnosed hypertensive patients. METHODS: Using province-wide linked administrative health data in Alberta, we analyzed a cohort of 259,873 newly-diagnosed hypertensive patients from 2009 to 2015 who collectively had 11,863 incident hospitalizations for heart failure, myocardial infarction, and stroke. Linear multi-task logistic regression, neural multi-task logistic regression, random survival forest and Cox proportional hazard models were used to determine the number of event-free survivors at each time-point and to construct individual event-free survival probability curves. The predictive performance was evaluated by root mean squared error, mean absolute error, concordance index, and the Brier score. RESULTS: The random survival forest model has the lowest root mean squared error value at 33.94 and lowest mean absolute error value at 28.37. Machine learning methods provide similar discrimination and calibration in the personalized survival prediction of hospitalizations for cardiovascular events in patients with hypertension. Neural multi-task logistic regression model has the highest concordance index at 0.8149 and lowest Brier score at 0.0242 for the personalized survival prediction. CONCLUSIONS: This is the first personalized survival prediction for cardiovascular diseases among hypertensive patients using administrative data. The four models tested in this analysis exhibited a similar discrimination and calibration ability in predicting personalized survival prediction of hypertension patients.

New method for determining breast cancer recurrence-free survival using routinely collected real-world health data.

BACKGROUND: In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence. METHODS: Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review. RESULTS: In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan-Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P-values) were very similar. CONCLUSION: The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.

Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension.

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Frequency of laboratory testing and associated abnormalities in patients with hypertension.

Clinical practice guidelines recommend several routine laboratory tests in patients diagnosed with hypertension. However, the rates of clinically relevant laboratory abnormalities are unknown. Therefore, we conducted a retrospective cohort study using administrative and laboratory data of patients diagnosed with hypertension between April 2010 and March 2015 in Alberta, Canada. Laboratory investigations for renal function, serum electrolytes (sodium and potassium), low-density lipoprotein (LDL) cholesterol, and diabetes (fasting blood glucose and hemoglobin A1c), measured within 1 year of diagnosis, were examined, and the frequency of abnormalities determined. A total of 225 296 cases of incident hypertension were identified. Of these, 74.3% received at least one of the four guideline-recommended laboratory tests, but only 42.3% received all four tests. Patients who received any testing, compared to subjects who did not, were on average older (median age 55.9 vs 51.2 years, P < .001) and had more comorbidity (14.5% vs 2.8% with a Charlson comorbidity index ≥ 3, P < .001). Laboratory abnormalities with the potential to affect clinical decision-making were more common among multi-comorbid patients. Patients with renal dysfunction (6.7% vs 11.6%, 26.3%, P < .001), electrolyte abnormalities (9.8% vs 12.6%, 20.5%, P < .001), and diabetes (13.4% vs 25.1% vs 38.8%, P < .001) were found in patients with Charlson scores of 0 vs 1-2 vs ≥3, respectively. Our study found most patients diagnosed with hypertension received some laboratory testing, but rates of laboratory testing and frequency of abnormalities varied by clinical context. Testing and abnormalities detected were both more common among older patients and patients with comorbidities.

A peptide-based biological coating for enhanced corrosion resistance of titanium alloy biomaterials in chloride-containing fluids.

Titanium alloys are common materials in the manufacturing of dental and orthopedic implants. Although these materials exhibit excellent biocompatibility, corrosion in response to biological fluids can impact prosthesis performance and longevity. In this work, a PEGylated metal binding peptide (D-K122-4-PEG), derived from bacteria Pseudomonas aeruginosa, was applied on a titanium (Ti) alloy, and the corrosion resistance of the coated alloy specimen was investigated in simulated chloride-containing physiological fluids by electrochemical impedance spectroscopy and micro-electrochemical measurements, surface characterization, and biocompatibility testing. Compared to uncoated specimen, the D-K122-4-PEG-coated Ti alloy demonstrates decreased corrosion current density without affecting the natural passivity. Morphological analysis using atomic force microscopy and scanning electron microscopy confirms a reduction in surface roughness of the coated specimens in the fluids. The D-K122-4-PEG does not affect the binding of HEK-293T cells to the surface of unpolished Ti alloy, nor does it increase the leukocyte activation properties of the metal. D-K122-4-PEG represents a promising coating to enhance the corrosion resistance of Ti alloys in physiological fluids, while maintaining an excellent biocompatibility.

Peptide-based biocoatings for corrosion protection of stainless steel biomaterial in a chloride solution.

In this work, PEGylated D-amino acid K122-4 peptide (D-K122-4-PEG), derived from the type IV pilin of Pseudomonas aeruginosa, coated on 304 stainless steel was investigated for its corrosion resistant properties in a sodium chloride solution by various electrochemical measurements, surface characterization and molecular dynamics simulation. As a comparison, stainless steel electrodes coated with non-PEGylated D-amino acid retroinverso peptide (RI-K122-4) and D-amino acid K122-4 peptide (D-K122-4) were used as control variables during electrochemical tests. It was found that the D-K122-4-PEG coating is able to protect the stainless steel from corrosion in the solution. The RI-K122-4 coating shows corrosion resistant property and should be investigated further, while the D-K122-4 peptide coating, in contrast, shows little to no effect on corrosion. The morphological characterizations support the corrosion resistance of D-K122-4-PEG on stainless steel. The adsorption of D-K122-4 molecules occurs preferentially on Fe2O3, rather than Cr2O3, present on the stainless steel surface.

Characterization of the complete mitochondrial genome and phylogenetic relationship of Neodon sikimensis (Rodentia: Arvicolinae).

The Sikkim Mountain vole (Neodon sikimensis) belongs to the subfamily Arvicolinae. In this study, we sequenced the complete mitochondrial genome of N. sikimensis. It was determined to be 16,330 bp long and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. The nucleotide sequence data of 12 heavy-strand protein-coding genes of N. sikimensis and other 22 rodents were used for phylogenetic analysis. Tree constructed using Bayesian phylogenetic methods demonstrated that N. sikimensis was a sister to N. irene, and Microtus genus species did not cluster together with each other, making the genus a paraphyletic group.