Risk Of Major Adverse Events Research Articles

Income-Based Disparities in Outcomes Following Pediatric Appendectomy: A National Analysis.

Appendectomy remains a common pediatric surgical procedure with an estimated 80,000 operations performed each year. While prior work has reported the existence of racial disparities in postoperative outcomes, we sought to characterize potential income-based inequalities using a national cohort. All non-elective pediatric (<18years) hospitalizations for appendectomy were tabulated in the 2016-2020 National Inpatient Sample. Only those in the highest (HI) and lowest income (LI) quartiles were considered for analysis. Multivariable regression models were developed to assess the independent association of income and postoperative major adverse events (MAE). Of an estimated 87,830 patients, 36,845 (42.0%) were HI and 50,985 (58.0%) were LI. On average, LI patients were younger (11 [7-14] vs 12 [8-15] years, P < .001), more frequently insured by Medicaid (70.7 vs 27.3%, P < .05), and more commonly of Hispanic ethnicity (50.8 vs 23.4%, P < .001). Following risk adjustment, the LI cohort was associated with greater odds of MAE (adjusted odds ratio [AOR] 1.30 95% confidence interval [CI] 1.06-1.64). Specifically, low-income status was linked with increased odds of infectious (AOR 1.65, 95% CI 1.12-2.42) and respiratory (AOR 1.67, 95% CI 1.06-2.62) complications. Further, LI was associated with a $1670 decrement in costs ([2220-$1120]) and a +.32-day increase in duration of stay (95% CI [.21-.44]). Pediatric patients of the lowest income quartile faced increased risk of major adverse events following appendectomy compared to those of highest income. Novel risk stratification methods and standardized care pathways are needed to ameliorate socioeconomic disparities in postoperative outcomes.

Influence of a surgeon's exposure to operating room turnover delays on patient outcomes.

A surgeon's daily performance may be affected by operating room organizational factors, potentially impacting patient outcomes. The aim of this study was to investigate the link between a surgeon's exposure to delays in starting scheduled operations and patient outcomes. A prospective observational study was conducted from 1 November 2020 to 31 December 2021, across 14 surgical departments in four university hospitals, covering various surgical disciplines. All elective surgeries by 45 attending surgeons were analysed, assessing delays in starting operations and inter-procedural wait times exceeding 1 or 2 h. The primary outcome was major adverse events within 30 days post-surgery. Mixed-effect logistic regression accounted for operation clustering within surgeons, estimating adjusted relative risks and outcome rate differences using marginal standardization. Among 8844 elective operations, 4.0% started more than 1 h late, associated with an increased rate of adverse events (21.6% versus 14.4%, P = 0.039). Waiting time surpassing 1 h between procedures occurred in 71.4% of operations and was also associated with a higher frequency of adverse events (13.9% versus 5.3%, P < 0.001). After adjustment, delayed operations were associated with an elevated risk of major adverse events (adjusted relative risk 1.37 (95% c.i. 1.06 to 1.85)). The standardized rate of major adverse events was 12.1%, compared with 8.9% (absolute difference of 3.3% (95% c.i. 0.6% to 5.6%)), when a surgeon experienced a delay in operating room scheduling or waiting time between two procedures exceeding 1 h, as opposed to not experiencing such delays. A surgeon's exposure to delay before starting elective procedures was associated with an increased occurrence of major adverse events. Optimizing operating room turnover to prevent delayed operations and waiting time is critical for patient safety.

Role of Mechanical Circulatory Support in Complex High-Risk and Indicated Percutaneous Coronary Intervention: Current Indications, Device Options, and Potential Complications.

Improved expertise and technological advancements have enabled the safe and effective performance of complex and high-risk-indicated percutaneous coronary intervention (CHIP) in patients previously considered inoperable or high-risk. Mechanical circulatory support (MCS) devices play a crucial role in stabilizing hemodynamics during percutaneous coronary intervention (PCI) -related ischemia, thereby reducing the risk of major adverse events and achieving a more complete revascularization. However, the use of MCS devices in protected PCI is not without risks, including peri-procedural myocardial infarction (MI), bleeding, and access-related complications. Despite numerous observational studies, there is a significant lack of randomized clinical trials comparing different MCS devices in various CHIP scenarios and evaluating their long-term safety and efficacy profiles. This review aims to summarize the current evidence regarding the benefits of MCS devices during CHIPs, offer a practical guide for selecting appropriate devices based on clinical scenarios, and highlight the unanswered questions that future trials need to address.

External validation of the ability of the mRENAL nephrometry score to identify patients at risk for major adverse events or local tumor recurrence after percutaneous renal cryoablation.

The purpose of this study was to evaluate the ability of the mRENAL score to identify patients at risk of either major adverse events (AEs) and/or local tumor recurrence (LR) after percutaneous cryoablation (PCA) in an external patient population. Patient demographic data were recorded. The RENAL and mRENAL nephrometry scores were calculated. Clinical outcomes such as AEs, LR, cancer-specific survival (CSS), and overall survival (OS) were collected. AEs were classified according to SIR criteria. Continuous variables and categorical variables were analyzed using the Wilcoxon rank sum test and chi-square test, respectively. Logistic regression analysis was performed to identify variables associated with major AEs or LR. The study included 207 patients (Males: n = 117 (56.5%)) with a mean age of 65.8 (± 11.2) years (range:27-90). Overall, the mean tumor diameter, RENAL score, and mean mRENAL score were 30.1mm (± 11.4), 6.3 (± 1.7), and 6.8 (± 1.9), respectively. 14 patients (6.8%) and 13 patients (6.3%) experienced a major AE or LR after PCA, respectively. CSS and OS were 98.6% and 90.3%, respectively. For patients with major AEs after PCA, the mean tumor diameter (p < 0.0001), mean RENAL score (p = 0.03), and mean mRENAL score (p = 0.009) were all higher than those for patients without a major AE. Multi-variate regression analysis showed that only mean tumor diameter (p = 0.005) was predictive of a major AE. There were no statistically significant differences between patients with LR and patients without LR after PCA with regards to tumor size (p = 0.07), mean RENAL score (p = 0.32), or mean mRENAL score (p = 0.07). Multi-variate regression analysis showed that only mean tumor diameter (p = 0.01) was predictive of LR. The mRENAL score did not accurately identify patients at risk for either major AEs or LR. Maximum tumor diameter alone was predictive of both major AEs and LR, and should be the primary focus during patient selection.

Unchanged incidence of major adverse events amidst rising surgical interventions for osteoporotic vertebral fractures, 2015-2021.

Osteoporotic vertebral fracture (OVF) is a common condition in the aging population, often leading to increased morbidity and mortality. Here, we analyzed treatment trends and incidence of major adverse events in patients hospitalized for OVF. We conducted a cross-sectional descriptive study, using a large Japanese hospital administrative database. The cohort included hospitalized patients aged 65years or older, admitted for OVF from January 2015 to December 2021. The primary outcomes were the trend in the proportion of the patients undergoing surgery for OVF and the incidence of major adverse events within 30days of admission. As a secondary outcome, we evaluated the trend in hospitalization costs. The study cohort consisted of 14,714 patients, with a mean age of 82.4years. There was a significant increase in surgical interventions for OVF, from 3.7% of patients in 2015 to 9.8% in 2021 (p < 0.001). The incidence of major adverse events remained unchanged, with a risk ratio of 1.09 (95% confidence interval, 0.88 to 1.35) in 2021 compared to 2015. Average hospitalization costs increased significantly, from $7,570.6 (SD 6,047.0) in 2015 to $9,502.9 (SD 7,231.5) in 2021 (p < 0.001). Despite a significant increase in the proportion of surgical intervention for OVF, no reduction in the risk of major adverse events was observed between 2015 and 2021. Surgeons and policy makers need to interpret these findings and work towards an optimized approach to the management of OVF in the aging population.

Reoperative aortic root replacement following previous cardiac surgery or type A aortic dissection repair

ObjectiveReoperative aortic root replacement (ARR) is a technically challenging procedure. This study assesses the influence of reoperation on outcomes following ARR, particularly after prior acute type A aortic dissection repair. MethodsOf the 1823 patients in this study, 1592 (87.3%) underwent primary ARR, and 231 (12.7%) underwent reoperative ARR. Within the reoperative ARR group, 69 patients (29.9%) had previous acute type A aortic dissection repair, and 162 patients (70.1%) underwent reoperative ARR for other indications. ResultsReoperative ARR patients exhibited higher rates of ischemic heart disease (13.9% vs 3%; P < .001), diabetes (10% vs 5.3%; P = .009), chronic pulmonary disease (9.1% vs 5%; P = .018), renal impairment (17.7% vs 5.3%; P < .001), and had lower ejection fraction (45.5% ± 8.1% vs 47.6% ± 7.9%; P < .001) compared with primary ARR. The overall operative mortality was 0.4%, with no significant difference between groups (0.9% vs 0.3%; P = .485). At multivariable analysis, previous operation was the most powerful predictor for major adverse events (odds ratio, 3.20; 95% CI, 2.12-4.79; P < .001). Reoperative ARR had a lower 10-year survival compared with primary ARR (67.4% vs 85.9%; log-rank P < .001). Multivariable analysis further confirmed that reoperation was significantly associated with 10-year mortality (hazard ratio, 1.76; 95% CI, 1.01-3.06; P = .044). Among the reoperative ARR group, operative mortality after previous acute type A aortic dissection repair was similar to that for other etiologies (0% vs 1.2%; P = .880). ConclusionsPatients undergoing reoperative ARR have more comorbidities and extensive aortic disease compared with those undergoing primary surgery. They face a 3.5-fold increased risk of major adverse events but no difference in operative mortality compared with primary ARR.

Timing of Noncardiac Surgery Following Transcatheter Aortic Valve Replacement: A National Analysis

BackgroundThe optimal timing of noncardiac surgery (NCS) following transcatheter aortic valve replacement (TAVR) for aortic stenosis has not been elucidated by current national guidelines. ObjectivesThe aim of this study was to evaluate the effect of the time interval between TAVR and NCS (Δt) on the perioperative risk of major adverse events (MAEs). MethodsAll adult admissions for isolated TAVR for aortic stenosis were identified in the 2016 to 2020 Nationwide Readmissions Database. Patients who received NCS on subsequent admission were included for analysis and grouped by Δt as follows: ≤30, 31 to 60, 61 to 90, and >90 days. Multivariable regression models were constructed to examine the association of Δt with ensuing outcomes. ResultsOf 3,098 patients (median age = 79 years, 41.6% female), 19.1% underwent NCS at ≤30 days, 22.9% at 31 to 60 days, 16.7% at 61 to 90 days, and 41.3% at >90 days. After adjustment, the odds of MAEs were similar for operations performed at ≤30 days (adjusted OR [AOR]: 1.05; 95% CI: 0.74-1.50), 31 to 60 days (AOR: 0.97; 95% CI: 0.71-1.31), and 61 to 90 days (AOR: 0.95; 95% CI: 0.67-1.34), with those at >90 days as reference. When examining the average marginal effect of the interval to surgery, risk-adjusted MAE rates were statistically similar across Δt groups for elective status and NCS risk category combinations. ConclusionsNCS within 30, 31 to 60, or 61 to 90 days after TAVR was not associated with increased odds of MAEs compared with operations after 90 days irrespective of NCS risk category or elective status. Our findings suggest that the interval between NCS and TAVR may not be an accurate predictor of MAE risk in this population.

The addition of peripheral nerve blocks to routine spinal or general anesthesia was associated with decreased risks of major adverse events after total hip or knee arthroplasty: A retrospective, propensity score-matched cohort study

BackgroundAlthough total joint arthroplasty is the most effective procedures for end-stage arthritis, the incidence of postoperative death and complications remains high. The association of additional peripheral nerve blocks (PNBs) to routine spinal or general anesthesia with major adverse events (including mortality and complication rates) in elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) has been subject to inconclusive findings. MethodsThis retrospective observational single institution study included all patients ≧ 18 years undergoing their first elective THA or TKA from January 1, 2012 to December 31, 2021. A 1:2 propensity score matching (PSM) was performed to account for the baseline differences between two groups that were accepted to PNB or not. Kaplan–Meier curves were employed to estimate the effects of PNB on mortality. The associations of PNB and the complications were assessed by logistic regression models. ResultsWe identified 1328 patients, among whom 197 had PNB and 1131 had not. The 90-day all-cause mortality was significantly reduced in patients with PNBs (0 % vs 2.79 %, P = 0.041) after THA or TKA, when compared to the non-PNB group. PNB was also associated with a lower risk of pulmonary complications (odds ratio [OR], 0.430; 95%confidence interval [CI],0.216–0.857) and deep vein thrombosis (OR, 0.103; 95%CI, 0.011–0.954). InterpretationThe results of this observational, propensity score–matched cohort study suggested a strong association between the addition of PNBs to routine spinal or general anesthesia and decreased risks of major adverse events.

Patient-reported treatment burden: comparison between vitamin-K antagonist and non-vitamin K antagonist oral anticoagulants

Abstract Introduction Treatment burden (TB) is defined as the overall workload that maintenance or improvement of their functioning and well-being poses on patients with chronic medical conditions. A high patient-reported TB has been associated with lower adherence to treatment and increased risk of major adverse events including death. We explored the differences in patient-reported TB value and prevalence of unacceptably high TB score (≥59 points) between patients receiving vitamin K antagonist oral anticoagulants (VKA) and non-vitamin K antagonist oral anticoagulants (NOAC). Furthermore, we explored contributory factors associated with TB and the relationship between TB and quality of life (QoL) in these patients. Methods A single-centre study included consecutive adult in- and outpatients on long-term oral anticoagulation, seen at a university clinical centre a from April to June 2019, who were willing to complete the Treatment Burden Questionnaire encompassing 13 items assessing the TB associated with taking medicine, self-monitoring, laboratory assessments, medical consultations, organisational and administrative requirements, adherence to dietary and physical activity recommendations, as well as the social repercussions of the treatment. Results Of 320 enroled patients, 206 (64.4%) were taking a VKA. Atrial fibrillation was the most common indication for long-term oral anticoagulation (n=299, 93.4%). The mean TB score was significantly higher in patients on VKA versus those taking a NOAC (48.8 ±26.5 vs. 41.8 ±19.7, P= 0.014), mostly owing to significantly higher TB values for questions related to self-monitoring, including the International Normalized Ratio (INR) control (3.85±3.32 vs. 1.62±1.38, P&amp;lt;0.001) and diet restrictions (3.98±3.43 vs. 2.48±2.49, P&amp;lt;0.001) in patients taking VKA (Figure 1). In addition, these patients significantly more often reported an unacceptably high TB of ≥59 points compared with those taking NOAC (30.1% vs 18.4%, P= 0.024). Multivariable regression analysis of predictors of TB in patients taking a VKA or NOAC are presented in Table 1. Conclusion In our study, patients receiving a VKA reported significantly higher TB compared to those using NOAC, especially regarding the questions about self-monitoring (including INR control) and diet restrictions. An unacceptably high TB was also more prevalent among patients receiving a VKA. Our findings suggest that prescribing NOACs in preference to VKAs could help in decreasing the self-reported TB in patients who need oral anticoagulant therapy.

#691 Validation of a prognostic model for adverse events in advanced chronic kidney disease in the Chinese population

Abstract Background and Aims Currently, the Grams model has been developed to estimate risks of adverse events among advanced chronic kidney disease (CKD) patients in western populations. Its utility is noteworthy as it predicts multiple adverse events within a single model while taking competing risks into account. While no external validation has been conducted among Asian, especially Chinese population, restricting further practical application and clinical benefits evaluation. Hence, we aimed to validate the performance of Grams model for estimating risks of major adverse events among Chinese CKD population. Method The Grams model was validated in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a multicenter prospective cohort study which involved 39 renal departments of 39 hospitals from 28 cities of 22 provinces in China. Participants with estimated glomerular filtration rate (eGFR) &amp;lt;30 ml/min/1.73 m2 during baseline and follow-up were enrolled. The same predictors as those selected in the Gram model were considered, including age, sex, race, history of cardiovascular disease(CVD), smoking status, systolic blood pressure, diabetes mellitus, eGFR, and urine albumin-to-creatinine ratio (uACR). The outcomes included kidney replacement therapy(KRT), CVD and death within 2- and 4- year follow-up periods. The discrimination and calibration of the model were evaluated using the concordance index (C index), the ratio of observed and expected outcomes (O/E ratio), and the calibration curve. The clinical utility of the model was assessed through decision curve analysis. Intercept recalibration was used to update the model. Results Among 1333 included participants (54 (IQR, 43-64) years, 699(52.4%) male), 386(29.0%) developed KRT, 118(8.9%) developed CVD, 88(6.6%) died during the follow-up period. The Grams model showed a moderate to good discrimination for three outcomes, with the C index ranging from 0.656 to 0.720. According to the O/E ratios and calibration curves, the calibration for KRT was relatively accurate, but the model overestimated the predicted probability of CVD and death. Intercept recalibration led to closer alignment of observed and predicted risks. Decision curve analyses revealed the superior net benefit of the Grams model in guiding KRT preparation. Conclusion In summary, the Grams model exhibited moderate discrimination for predicting outcomes, with relatively accurate calibration for KRT but an overestimation of predicted probabilities for CVD and death, intercept recalibration improved the calibration of the model. Despite its limitations, the model offered a superior net benefit in guiding KRT preparation, suggesting its potential use in clinical decision-making process. Further investigations are warranted to improve the performance of the Grams model in Chinese population.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography

BackgroundCardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. MethodsThe study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. ResultsDetectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45–1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39–1.90) for the first tertile to 2.02 (95 % CI 1.74–2.35) for the third tertile. ConclusionsDetectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Same-day discharge after percutaneous coronary procedures-Consensus statement of the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology.

Percutaneous coronary intervention is awell-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and aclear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns. The aim of this consensus statement is to provide apractical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on astructured literature review and an in-depth analysis of available practice guidelines aconsensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology. Based on the available literature same-day discharge coronary procedures show afavorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides adetailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and astructured peri-interventional and postinterventional management plan. Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria.

Same-day discharge after percutaneous coronary procedures-Structured review and comprehensive meta-analysis.

Percutaneous coronary intervention is awell-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on asame-day discharge basis for selected patients has been studied in alarge number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries. The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. Astructured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures. Atotal of 44clinical trials and 4large meta-analyses were retrieved, spanning 21years of clinical evidence from 2001 to 2022. The outcome data from awide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials acomprehensive meta-analysis was compiled. Using 1‑month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I2 0%), indicating a noninferiority in carefully selected patients. Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.

Trends in the adoption of diverting loop ileostomy for acute complicated diverticulitis in the United States

BackgroundAcute complicated diverticulitis poses a substantial burden to individual patients and the health care system. A significant proportion of the cases necessitate emergency operations. The choice between Hartmann’s procedure and primary anastomosis with diverting loop ileostomy remains controversial. MethodsUsing American College of Surgeons National Surgical Quality Improvement Program patient user file data from 2012 to 2020, patients undergoing Hartmann’s procedure and primary anastomosis with diverting loop ileostomy for nonelective sigmoidectomy for complicated diverticulitis were identified. Major adverse events, 30-day mortality, perioperative complications, operative duration, reoperation, and 30-day readmissions were assessed. ResultsOf 16,921 cases, 6.3% underwent primary anastomosis with diverting loop ileostomy, showing a rising trend from 5.3% in 2012 to 8.4% in 2020. Primary anastomosis with diverting loop ileostomy patients, compared to Hartmann’s procedure, had similar demographics and fewer severe comorbidities. Primary anastomosis with diverting loop ileostomy exhibited lower rates of major adverse events (24.6% vs 29.3%, P = .001). After risk adjustment, primary anastomosis with diverting loop ileostomy had similar risks of major adverse events and 30-day mortality compared to Hartmann’s procedure. While having lower odds of respiratory (adjusted odds ratio 0.61, 95% confidence interval 0.45–0.83) and infectious (adjusted odds ratio 0.78, 95% confidence interval 0.66–0.93) complications, primary anastomosis with diverting loop ileostomy was associated with a 36-minute increment in operative duration and increased odds of 30-day readmission (adjusted odds ratio 1.30, 95% confidence interval 1.07–1.57) compared to Hartmann’s procedure. ConclusionPrimary anastomosis with diverting loop ileostomy displayed comparable odds of major adverse events compared to Hartmann’s procedure in acute complicated diverticulitis while mitigating infectious and respiratory complication risks. However, primary anastomosis with diverting loop ileostomy was associated with longer operative times and greater odds of 30-day readmission. Evolving guidelines and increasing primary anastomosis with diverting loop ileostomy use suggest a shift favoring primary anastomosis, especially in complicated diverticulitis. Future investigation of disparities in surgical approaches and patient outcomes is warranted to optimize acute diverticulitis care pathways.

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

The use of mechanical circulatory support in elective high-risk percutaneous coronary interventions: a literature-based review.

Contemporary medical practices allow complete percutaneous coronary intervention (PCI) in a considerable number of patients who previously would have been considered too 'high-risk' for such procedures. The use of mechanical circulatory support (MCS) devices during these high-risk PCIs (HR-PCIs) is thought to reduce the potential risk for major adverse events during and after revascularization. The intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), and the Impella are the most common MCS devices in use. This review aims to summarize the clinical evidence for each of these devices and the potential mechanisms for the improvement in patient outcomes in HR-PCI. The IABP use has rapidly declined in recent years due to no evidence of benefit in HR-PCI and cardiogenic shock. The V-A ECMO results in low rates of major adverse cardiac and cerebrovascular events (MACCEs) but higher rates of acute kidney injury and increased need for transfusions. In initial studies, Impella resulted in a reduced need for repeat interventions and reduced rates of hypotension, but no benefit in mortality. However, MACCE rates with Impella have gradually declined over the last 10 years, reflecting increased operator experience and technical improvements. Thus, a large, randomized trial is needed to assess the efficacy of Impella in HR-PCI with contemporary standards of care. There is currently no individual parameter that can identify patients who would benefit from MCS use in elective HR-PCI. To address this gap, we propose an algorithm that combines anatomical complexity, comorbidities, and clinical presentation to accurately identify candidates for MCS-assisted HR-PCI.

Comparative Safety of Pulsed Field Ablation and Cryoballoon Ablation Technologies for Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation: A Critical Literature Review and Indirect Treatment Comparison.

Cryoballoon ablation (CBA) is a standard catheter ablation technology with demonstrated clinical effectiveness for the treatment of paroxysmal atrial fibrillation (PAF); however, it can be associated with major adverse events, including phrenic nerve paralysis. Pulsed field ablation (PFA) is a novel, minimally thermal technology with comparable effectiveness and low safety risk. This study aimed to compare the safety profiles of PFA and CBA through critical analyses of the literature and indirect treatment comparisons. Studies were identified by searching the MEDLINE database and the Clinicaltrials.gov registry. Registered clinical trials and/or Food and Drug Administration Investigation Device Exemption (FDA IDE) studies evaluating PFA or CBA in adult patients with drug-refractory PAF between January 2008 and March 2023 were selected. Comparative safety between PFA and CBA was assessed for major and prespecified adverse events. Indirect comparisons were conducted using the proportion of patients experiencing adverse events and confirmed with single-arm meta-analyses and sensitivity analyses. Data were extracted from three PFA publications including a total of 497 patients and six CBA studies including a total of 1113 patients. The analysis revealed that PFA was associated with significantly lower risk of major adverse events {risk difference-4.3% [95% confidence interval (CI)-5.8,-2.8]; risk ratio 0.16 [95% CI 0.07, 0.45]} and prespecified adverse events [risk difference -2.5% (95% CI-4.4,-0.5); risk ratio 0.53 (95% CI 0.31, 0.96)]. Meta-analyses confirmed the lower rate of major adverse events for PFA [0.4% (95% CI 0.0, 1.3)] vs. CBA [5.6% (95% CI 2.6, 8.6)] and prespecified adverse events for PFA [2.7% (95% CI 1.2, 4.1)] vs. CBA [5.8% (95% CI 2.7, 9.0)]. Sensitivity analyses exploring heterogeneity across studies confirmed robustness of the main analyses. The findings of this study show that PFA has a more favorable safety profile than CBA, with significantly lower risks of major and prespecified adverse events. These indirect comparisons help contextualize the safety of PFA compared to CBA for the treatment of drug-refractory PAF in the absence of head-to-head studies.

Safety profile and adherence to treatment with ocrelizumab in multiple sclerosis – long-term observations

Among the available disease modifying drugs used in the treatment of multiple sclerosis, there is an increasing relevance of high-efficacy therapies recommended for early use to control the disease activity effectively. In the course of treatment, efficacy as well as safety measures of high-efficacy therapies have to be regularly evaluated. Ocrelizumab, an anti-CD20+ antibody, is the only high-efficacy therapy approved for the treatment of both relapsing-remitting and primary progressive type of multiple sclerosis. Consequently, the drug can be used in a wide population of multiple sclerosis patients. Recently, the cumulative data have been acquired from 10-year follow-up of ocrelizumab use in clinical trials and real-world evidence in as many as 300,000 patients with multiple sclerosis. Based on these data, the general safety profile of the drug has been reviewed (considering the risk of major adverse events, including infusion-related reactions, infections and malignancies), along with specific aspects associated with vaccines and pregnancy/post-partum period. Moreover, the indices of adherence and persistence in long-term treatment with ocrelizumab have been analysed, together with their potential contributing factors. The above data indicate that treatment with ocrelizumab has a beneficial safety profile and is well-tolerated by patients with multiple sclerosis, which supports the choice of ocrelizumab as a therapeutic option. Ongoing clinical and observational trials and registries will provide further data on the safety of the drug, which would allow an update of recommendation in this field.

How Good Are Cardiologists at Predicting Major Adverse Events in Fontan Patients?

BackgroundIt is unknown how well cardiologists predict which Fontan patients are at risk for major adverse events (MAEs). ObjectivesThe purpose of this study was to examine the accuracy of cardiologists' ability to identify the “good Fontan” patient, free from MAE within the following year, and compare that predicted risk cohort to patients who experienced MAE. MethodsThis prospective, multicenter study included patients ≥10 years with lateral tunnel or extracardiac Fontan. The cardiologist was asked the yes/no “surprise” question: would you be surprised if your patient has a MAE in the next year? After 12 months, the cardiologist was surveyed to assess MAE. Agreement between cardiologist predictions of MAE and observed MAE was determined using the simple kappa coefficient. Multivariable generalized linear mixed effects models were performed to identify factors associated with MAE. ResultsOverall, 146 patients were enrolled, and 99/146 (68%) patients w`ere predicted to be a “good Fontan.” After 12 months, 17 (12%) experienced a MAE. The simple kappa coefficient of cardiologists’ prediction was 0.17 (95% CI: 0.02-0.32), suggesting prediction of MAE was 17% better than random chance. In the multivariable cardiologist-predicted MAE (N = 47) model, diuretic/beta-blocker use (P ≤ 0.001) and systolic dysfunction (P = 0.005) were associated with MAE. In the observed multivariable MAE (N = 17) model, prior unplanned cardiac admission (P = 0.006), diuretic/beta-blocker use (P = 0.028), and ≥moderate atrioventricular valve regurgitation (P = 0.049) were associated with MAE. ConclusionsCardiologists are marginally able to predict which Fontan patients are at risk for MAE over a year. There was overlap between factors associated with a cardiologist’s prediction of risk and observed MAE, namely the use of diuretic/beta-blocker.

Clinical Phenotyping with an Outcomes-driven Mixture of Experts for Patient Matching and Risk Estimation.

Observational medical data present unique opportunities for analysis of medical outcomes and treatment decision making. However, because these datasets do not contain the strict pairing of randomized control trials, matching techniques are to draw comparisons among patients. A key limitation to such techniques is verification that the variables used to model treatment decision making are also relevant in identifying the risk of major adverse events. This article explores a deep mixture of experts approach to jointly learn how to match patients and model the risk of major adverse events in patients. Although trained with information regarding treatment and outcomes, after training, the proposed model is decomposable into a network that clusters patients into phenotypes from information available before treatment. This model is validated on a dataset of patients with acute myocardial infarction complicated by cardiogenic shock. The mixture of experts approach can predict the outcome of mortality with an area under the receiver operating characteristic curve of 0.85 ± 0.01 while jointly discovering five potential phenotypes of interest. The technique and interpretation allow for identifying clinically relevant phenotypes that may be used both for outcomes modeling as well as potentially evaluating individualized treatment effects.