Composite Outcome Research Articles

The Win Ratio for Composite Outcomes in Nephrology Clinical Trials.

The Win Ratio for Composite Outcomes in Nephrology Clinical Trials.

Decoupling Intrinsic Metal Ion Reduction Rates from Structural Outcomes in Multimetallic Nanoparticles.

Simultaneously controlling both stoichiometry and atom arrangement during the synthesis of multimetallic nanoparticles is often challenging, especially when the desired metal precursors exhibit large differences in their intrinsic reduction kinetics. In such cases, traditional synthetic methods often lead to the formation of exclusively phase-segregated structures. In this study, we demonstrate that the relative reduction kinetics of the metal precursors can be manipulated independently of their intrinsic differences in reduction rates by modulating the instantaneous concentrations of the metal cation precursors. We achieve this control by adjusting the precursor addition rate, which decouples chemical ordering outcomes from differences in precursor reduction kinetics. To guide these experiments, we describe a quantitative model to determine how metal ion reduction rates evolve with variations in the precursor addition rate and thereby predict optimal conditions for the synthesis of multimetallic nanoparticles with precise structural and compositional outcomes. We demonstrate the efficacy of this model experimentally by synthesizing both core@shell and alloyed nanoparticles with stoichiometric control using the same metal ion precursors in two different bimetallic systems (Au-Pd and Au-Pt) as well as in a quinary metal system (Co, Ni, Cu, Pd, and Pt). This approach enables the design of nanoparticle architectures independent of intrinsic differences in metal ion reduction potentials of the constituent metals while maintaining both stoichiometric and structural control.

Identifying subgroups benefiting from intensive glycaemic treatment to improve renal outcomes in type 2 diabetes: Insights from the ACCORD trial.

The ACCORD trial showed that intensive glucose-lowering therapy has a limited impact on renal function decline. We aimed to identify subgroups in the ACCORD population that might derive renal benefits from intensive glucose-lowering therapy. The primary renal outcome included a ≥50% decline in baseline estimated glomerular filtration rate or end-stage renal disease (ESRD). Using the causal tree model, we employed internal cross-validation to identify five pivotal variables influencing the renal efficacy of intensive glycaemic control. These variables were integrated into the model-based recursive partitioning approach, yielding a visualizable tree model that depicted benefitting subgroups. Node 4, characterized by no cardiovascular history, systolic blood pressure (SBP) ≤142.67 mm Hg, and triglycerides ≤172 mg/dL, showed significantly reduced hazards of the composite renal outcome (fully adjusted hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.49-0.89; p = 0.006) and doubling of serum creatinine (fully adjusted HR 0.59, 95% CI 0.36-0.98; p = 0.041). Node 7 (no cardiovascular history and SBP 142.67-154 mm Hg) showed reduced hazards of the primary renal outcome (fully adjusted HR 0.67, 95% CI 0.49-0.93; p = 0.016) and ESRD (fully adjusted HR 0.35, 95% CI 0.17-0.74; p = 0.0057). Encouragingly, neither node 4 nor node 7 displayed elevated cardiovascular risk or hypoglycaemic events. Through innovative machine learning, we identified ACCORD subgroups benefitting significantly from intensive glycaemic therapy for renal outcomes, without increased cardiovascular or hypoglycaemic risks.

Serum Neutrophil Biomarkers to Predict Crohn's Disease Progression and Infliximab Treatment Outcomes.

Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting. The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin-2, lactoferrin, and resistin (non-neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA. Over up to 2years of follow-up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p<0.001), lipocalin-2 (p<0.001), and lactoferrin (p<0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75-0.85); all other correlations were of small magnitude. Our real-world data do not support using serum neutrophil elastase, lipocalin-2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab -treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.

MELD score predicts outcomes in patients with advanced heart failure: A longitudinal evaluation.

Advanced heart failure (AHF) is characterized by recurrent episodes of haemodynamic instability and frequent hospitalizations, leading to a progressive decline in quality of life and high mortality rates. The objectives of this study were to evaluate the effect of the model for end-stage liver disease (MELD) score and its variations in predicting adverse outcomes [death, urgent heart transplant, and left ventricular assist device (LVAD) implant] among patients with AHF to assess the clinical associations of the MELD score in this population and to compare the efficacy of this tool with other prognostic scores in AHF. In this longitudinal prospective study, 162 patients with advanced heart failure (AHF) were enrolled; all patients included in the study were receiving the maximum tolerated medical therapy according to guidelines. The MELD score was measured at baseline and every 6months during follow-up. All patients underwent echocardiographic assessment and cardiopulmonary testing, which included the evaluation of maximal oxygen uptake (VO2max) and the minute ventilation/carbon dioxide production (VE/VCO2) slope. The mean age of the study group was 57.7±11.6years. There were 26 deaths, 5 urgent transplants, and 1 LVAD implantation during a follow-up period of 31.4±15.6months. The mean New York Heart Association (NYHA) class was 2.8±0.5, ejection fraction (EF) was 26.3±6.5%, the mean VO2max was 11.7±3.5mL/kg/min. Multiple regression analysis revealed a positive correlation between the MELD score and NT-proBNP (β=0.215; P=0.041) and furosemide dosage (β=0.187; P=0.040). Conversely, a negative correlation was observed between the MELD score and TAPSE (β=-0.204; P=0.047). Multivariate Cox regression on combined outcome shows a HR of 1.094 (95% CI 1.003-1.196) for unit increase in MELD considered as a continuous variable. The predictive role is independent by the effect of covariates considered in the analysis such as age, sex, NYHA class, EF, TAPSE, PASP, VO2max, NT-proBNP, MELD score worsening, and NT-proBNP increase. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality, urgent heart transplant and LVAD implant. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.887 for MELD score and composite outcome of death, urgent transplant, and need for LVAD. The predictive performance of MELD was even superior compared with MELD-Na, MELD-XI, MAGGIC risk score, and MECKI. The MELD score and its longitudinal changes are effective predictors of adverse outcomes in AHF.

Adverse Outcomes After Tunneled Dialysis Catheter-Related Bloodstream Infections-Too Dark at the End of This Tunnel?

Tunneled dialysis catheters (TDCs) are preferred over temporary noncuffed catheters for access in patients on maintenance hemodialysis. The removal of TDC after catheter-related blood stream infections (CRBSIs) is often not practiced even when indicated, and the adverse outcomes after such salvage are presently unclear. The study aimed to evaluate adverse outcomes after the first episode of definite or probable CRBSI. The composite adverse outcome was recorded as the presence of at least one of three adverse outcomes-death in the index hospital admission, occurrence of recurrent bacteremia, and death within 3 months. During the study period, the TDC CRBSI incidence rate was 6.9/1000 catheter days. Of the 110 study participants, majority were male (63%), with a median age of 35 years, belonging to rural (56%) and agrarian (39%) communities, and 66% were getting dialyzed at stand-alone dialysis units. Gram-negative infections predominated (64%), with 37% of isolates showing resistance to carbapenems. Catheter salvage was practiced in 80%, and immediate catheter removal was done only in the sickest of patients (in seven of eight with in-hospital mortality). Predictors of composite adverse outcomes included sites other than right internal jugular vein (OR 3.6) and resistance to β lactam-β lactamase inhibitors (OR 16.2). At a median follow-up of 7 months, all survivors at 3 months were alive and 46% had recurrent TDC CRBSIs. Up to one-half of patients with end-stage kidney disease experienced composite adverse outcomes after the first episode of TDC CRBSI, with infection-related 3-month mortality of 15%. Clinical trial number: CTRI/2023/10/058556.

Early postnatal effects of maternal obesity on breast milk composition and breastfeeding outcomes.

Breastfeeding can be challenging in mothers with overweight or obesity-related chronic low-grade inflammation, resulting in negative consequences for the newborn. The pre-gestational body mass index is negatively associated with lactogenesis II, the onset of colostrum secretion. Herein, we evaluated mothers' inflammation, metabolic status, and components of breast milk after birth to associate these factors with their nutritional and breastfeeding status. The study included volunteer mothers, categorized based on their nutritional status and anthropometric parameters, who gave birth in a tertiary maternity hospital. Serum and breast milk samples were collected 24 and 48 hours after birth to determine inflammatory biomarkers (SAA, leptin, CRP, IL-1β, TNF-α, IL-8, IL-6, MCP-1, IL-10, and IFN-γ), reproductive hormones (prolactin and progesterone), as well as the breast milk composition (total protein, fatty acid, percentage of fat and Kcal). Furthermore, we conducted a six-month follow-up to assess breastfeeding outcomes. Interestingly, the composition of breast milk did not vary in the different situations analyzed, indicating the stability of the breast milk´s composition in meeting infant needs, regardless of age, nutritional status, and type of birth. Our findings revealed a higher concentration of pro-inflammatory biomarkers (SAA, CRP, TNF-α, IL-8, and IFN-γ) than anti-inflammatory, IL-10, in breast milk. Our study showed that mothers who were overweight after pregnancy had a newborn with a higher birth weight compared to healthy post-pregnancy weight. Our study elucidates the intricate dynamics between maternal weight, inflammation, and breastfeeding outcomes. While maternal overweight or obesity-related inflammation may pose challenges to lactogenesis II and influence newborn birth weight, breast milk remains a stable and reliable source of essential nutrients for infant nourishment. However, the presence of pro-inflammatory biomarkers in breast milk warrants further investigation into its potential implications for infant health.

Extracorporeal Photopheresis for the prevention of rejection after lung transplantation - a prospective randomized controlled trial.

Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). To investigate the efficacy of ECP as a prophylactic treatment to prevent acute cellular rejection (ACR), CMV infections and reduce the risk of CLAD. Single-center prospective randomized controlled trial conducted at Medical University of Vienna between 2018 and 2020. It included 31 COPD recipients per group. Treatment group underwent extracorporeal photopheresis in addition to standard triple-drug immunosuppression protocol after lung transplantation. Control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation. In the control group, 19 patients (61.3%) achieved the primary combined endpoint, compared with only 6 patients (19.4%) in the treatment group (p<0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44 versus 0.56±0.94, p<0.05) and at 12 months (0.25±0.48 versus 1.0±1.45, p=0.002). The rate of infections was lower in the ECP group with 5 cases and 67 cumulative hospital days compared to 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at three years was significantly greater in the ECP group (p=0.015). Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.

Early predictors of unfavorable outcomes in pediatric acute respiratory failure

ObjectiveAcute respiratory failure is a leading cause of critical illness in children. However, patient outcomes and early predictors of unfavorable outcomes are not well understood. This study aimed to describe composite unfavorable outcomes, defined as in-hospital death or discharge with new comorbidities, and to identify early predictors in children with acute respiratory failure in acute care hospitals.DesignRetrospective cohort study using a national inpatient database in Japan.SettingAll acute care hospitals registered in the database.PatientsThis study included children under 20 years of age who were admitted with acute respiratory diseases between July 2010 and March 2022 and received ventilatory support within the first three days of hospitalization.InterventionNone.Measurements and main resultsAmong 29,362 eligible children, the median age was 1.2 (interquartile range, 0.3–3.7) years and 28.8% had underlying conditions. The highest level of ventilatory support within the first three days was invasive ventilation (69.4%), noninvasive ventilation (1.0%), and high-flow nasal cannula (29.7%). Respiratory diagnoses included pneumonia (58.6%), bronchiolitis (29.0%), and asthma (11.1%). Among these children, 669 (2.3%) died and 1994 (6.8%) were discharged with new comorbidities, resulting in 2663 (9.1%) children experiencing unfavorable outcomes. In the logistic regression model, older age, underlying conditions, pneumonia, and low hospital volume were associated with unfavorable outcomes after adjusting for covariates.ConclusionsA significant proportion of pediatric patients with acute respiratory failure experienced unfavorable outcomes, warranting future efforts to improve acute care services for at-risk children. Early predictors identified from national database analyses could inform risk stratification and optimize the provision of acute care services for vulnerable pediatric patients.

Exploring Infant Size and Body Composition at 18 Months: An Ambidirectional Peri-Urban South African Cohort Study.

The first 1000 days of life lay the foundations for subsequent growth. This ambidirectional study, including prenatal, perinatal and postnatal factors, aimed to identify exposure variables affecting body size and composition and corresponding Z-score outcomes at age 18 months in infants born to women at low risk of adverse pregnancy outcomes in a peri-urban area of South Africa. Prenatal factors (maternal age, HIV status, anthropometry, parity, food insecurity and umbilical artery resistance index Z-score (UmA-RIAZ) as a measure of placental function, with higher UmA-RIAZ indicating poorer placental function); perinatal factors (infant sex, gestational age and birth anthropometry) and postnatal factors (infant feeding) were included as exposure variables, with infant anthropometry and body composition at 18 months as outcomes. Simple linear regression analysis was used to investigate associations between exposure variables and infant outcomes, and variables with p < 0.10 were included in the subsequent multiple regression analyses. Multiple regression analysis showed that higher UmA-RIAZ predicted lower birthweight [-0.11 kg (95% CI: -0.17, -0.04 kg)], birthweight-for-age Z-score [-0.24 (95% CI: -0.39, -0.09)] and 18-month infant length [-0.9 cm (95% CI: -1.4, -0.4 cm)] and length-for-age Z-score [-0.28 (95% CI: -0.45, -0.11)]. Maternal HIV infection predicted reduced 18-month infant length-for-age Z-score [-0.46 (95% CI: -0.83, -0.09)]. Household food insecurity predicted reduced fat-free mass-for-age Z-score at 18 months [-0.27 (95% CI: -0.51, -0.03)]. Infant anthropometry and body composition outcomes, therefore, are greatly affected by pre- and postnatal nutrition-related factors, such as placental insufficiency in utero and household food insecurity, with long-term consequences including stunting, which impact the individual, future generations and society.

Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Hypertension is a risk factor for the development and progression of chronic kidney disease (CKD). It is unclear whether different thiazide diuretics have a differential impact on kidney outcomes. To compare kidney outcomes in patients with hypertension taking chlorthalidone and hydrochlorothiazide. This prespecified secondary analysis of the Diuretic Comparison Project, a randomized clinical trial comparing chlorthalidone and hydrochlorothiazide for the treatment of hypertension, was conducted between June 1, 2016, and June 1, 2022, through Veterans Affairs facilities nationwide. This analysis extended follow-up to December 31, 2023. Veterans 65 years or older with hypertension who were taking hydrochlorothiazide were included. The Diuretic Comparison Project randomized 13 523 participants to continue hydrochlorothiazide or switch to chlorthalidone. The main kidney outcome was CKD progression, defined as doubling of serum creatinine level from baseline, a terminal estimated glomerular filtration rate (eGFR) less than 15 mL/min, or dialysis initiation. Analysis included 12 265 participants (90.7%) with a baseline and 1 or more follow-up creatinine measurements (median [IQR] age, 71 [69-75] years; 3.2% female and 96.8% male). The mean (SD) study duration was 3.9 (1.3) years. Chlorthalidone was not superior to hydrochlorothiazide at preventing kidney outcomes (369 of 6118 [6.0%] vs 396 of 6147 [6.4%]; hazard ratio [HR], 0.94; 95% CI, 0.81-1.08; P = .37). Similar results were observed when a 40% or greater reduction of eGFR was substituted for doubling of creatinine in the above outcome, as well as any of the components of the primary composite outcome. There was no difference in the incidence of CKD (961 of 4520 [21.3%] for chlorthalidone vs 939 of 4518 [20.8%] for hydrochlorothiazide; P = .59) or acute kidney injury requiring hospitalization (391 [6.4%] for chlorthalidone vs 379 [6.2%] for hydrochlorothiazide; P = .63) between groups. However, a statistically significant increased incidence of hypokalemia for chlorthalidone vs hydrochlorothiazide was observed (545 [8.9%] vs 426 [6.9%]; P < .001). Chlorthalidone was not superior to hydrochlorothiazide for kidney outcomes but was associated with an increased risk for hypokalemia. Given these findings, clinicians should feel confident using either agent for the treatment of hypertension and kidney outcomes. ClinicalTrials.gov Identifier: NCT02185417.

Prognostic importance of extensive coronary calcium on lung cancer screening chest computed tomography.

Low-dose chest computed tomography (CT) is used for lung cancer screening, but can also detect coronary artery disease as coronary artery calcium. We sought to determine the prevalence and prognostic utility of coronary artery calcium in a population at high risk of cancer. We reviewed CT scans from consecutive participants screened for lung cancer between March 2017 and November 2018 as part of the Ontario Health Lung Cancer Screening Pilot for People at High Risk. We quantified coronary artery calcium using an estimated Agatston score. We identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from The Ottawa Hospital to December 2023. Among 1486 people who underwent screening CT, coronary artery calcium was detected in 1232 (82.9%) and was extensive in 439 (29.5%). On multivariable analysis, extensive coronary artery calcium was associated with the composite primary outcome (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.35-3.38), all-cause death (HR 2.39, 95% CI 1.34-4.27), and cardiovascular events (HR 2.06, 95% CI 1.13-3.77). Extensive coronary artery calcium remained predictive of cardiovascular events after we adjusted for noncardiovascular death as a competing risk (HR 2.05, 95% CI 1.09-3.85). Among people undergoing low-dose chest CT for lung cancer screening, extensive coronary artery calcium was an independent predictor of all-cause death and cardiovascular events, even after adjustment for noncardiovascular death. The opportunity to identify and reduce risks from coronary artery disease may represent an additional benefit of lung cancer screening.

Validation of a holistic composite outcome measure for the evaluation of chronic pain interventions.

Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention. To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool. This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis. The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a "leave-one-out" analysis (all P < 0.001). The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions.

Kidney effects of Glucagon-Like Peptide 1 (GLP1): from molecular foundations to a pharmacophysiological perspective.

GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature.

Effect of perioperative blood transfusion on preoperative haemoglobin levels as a risk factor for long-term outcomes in patients undergoing major noncardiac surgery: a prospective multicentre observational study

BackgroundPreoperative anaemia and red blood cell (RBC) transfusions are associated with poorer clinical outcomes. It is unknown whether perioperative RBC transfusions mediate the relationship between preoperative haemoglobin levels and postoperative outcomes. MethodsThis was a prospective observational study among patients aged ≥50 yr undergoing elective major noncardiac surgery from four Swedish hospitals. The co-primary outcomes were 1-yr major adverse cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality. The secondary outcome was a composite of 30-day mortality, MACCEs, acute kidney injury (AKI), pulmonary embolism, anastomotic leak, and postoperative infection. Mediation analyses were conducted with preoperative haemoglobin as the exposure and RBC transfusion as a mediator. ResultsAmong 1060 patients (mean age 70 [SD 9] yr; 472 [45%] women), 171 patients (16.1%) developed 1-yr MACCEs, and 105 patients (9.9%) died within 1 yr. Preoperative haemoglobin levels were significantly associated with both 1-yr MACCEs (b=–0.015, P=0.041) and all-cause mortality (b=–0.028, P<0.001). Volume of RBC transfusion was not directly associated with the outcomes and did not mediate the relationship between preoperative haemoglobin levels and 1-yr MACCEs (b=–0.001, P=0.451) or all-cause mortality (b=–0.002, P=0.293). For the secondary outcome, RBC transfusions had a significant mediating effect between preoperative haemoglobin and the composite 30-day outcome; however, no direct association was observed (b=0.006, P=0.554). ConclusionsPreoperative haemoglobin levels were significantly associated with 1-yr MACCEs and all-cause mortality. This effect was not mediated by perioperative RBC transfusions. Further research is needed to confirm these findings.

Outcomes for women with diabetes admitted for labour care to midwifery units in the UK: a national prospective cohort study and survey of practice using the UK Midwifery Study System (UKMidSS)

ObjectivesTo describe outcomes in women admitted for labour care to midwifery units with gestational or pre-existing diabetes, compare outcomes with other women admitted to the same units and describe admission...

Optimal circulatory arrest temperature for total aortic arch replacement: outcomes of neurological complications

BackgroundThe optimal hypothermic circulatory arrest (HCA) temperature during total arch replacement (TAR) and the impact of HCA temperature on postoperative neurological complications are still uncertain. ObjectiveThe aim of this study is to explore the impact of HCA temperature on short-term postoperative outcomes, especially neurological complications, for patients who undergo TAR. MethodsWe retrospectively analyzed data of 2351 patients who underwent TAR at one of seven selected aortic centers from January 2016 to June 2023. Restricted cubic splines (RCS) and subgroup analyses were performed to determine the relation between temperature and outcomes under different cerebral perfusion methods, cannulation strategies, diagnoses, and surgical timings. ResultsThe overall in-hospital mortality was 6.2% (n = 146). The incidence of stroke, paraplegia and total-arch composite outcome (TCO) was 6.0% (n = 142), 2.8% (n = 65) and 21.0% (n = 494), respectively. The average HCA temperature was 25.9 ± 1.9 °C, and the median circulatory arrest time was 23 (Q1, Q3: 18, 30) min. Adjusted RCS showed the lowest incidence of stroke, paraplegia, and TCO at temperatures of 26.6 °C, 27.4 °C, and 26.8 °C, but without statistical significance. In subgroup analysis, the unilateral antegrade cerebral perfusion (uACP) group revealed a significant nonlinear relation between HCA temperature and the risk of stroke, and the lowest risk showed at 26.5 °C. Other subgroup analyses did not reveal a significant nonlinear relation between temperature and outcomes. ConclusionsFor patients undergoing TAR with uACP, cooling to a temperature of 26-27 °C was associated with the lowest incidence of stroke.

Clinical effectiveness of oral antivirals for non-hospitalized adult COVID-19 patients aged 18–60 years

ABSTRACT Objective To investigate the effectiveness of oral antiviral agents – nirmatrelvir – ritonavir or molnupiravir in non-hospitalized COVID-19 patients aged <60 years. Methods This retrospective cohort study analyzed data of patients aged 18–60 years diagnosed with COVID-19 between 1 January 2022, and 30 June 2023. Propensity score matching was used to balance the demographic and clinical characteristics of patients receiving oral antivirals (nirmatrelvir – ritonavir or molnupiravir) and untreated controls. The primary outcome was a composite of all-cause emergency department visits, hospitalizations, or mortality within 30 days. The secondary outcomes included each individual component of the primary composite outcome. Results Two matched cohorts (antiviral group and control group) comprising 52,585 patients with balanced baseline characteristics were created using propensity score-matching. During follow-up period, the antiviral group demonstrated a lower risk of the primary outcome than the control group (hazard ratio [HR] 0.772, 95% confidence interval [CI] 0.736–0.808, p < 0.001). The antiviral group also exhibited a reduced risk of individual secondary outcomes, including emergency department visits (HR 0.780, 95% CI, 0.738–0.825), hospitalization (HR 0.755, 95% CI, 0.715–0.840), and mortality (HR 0.297, 95% CI, 0.147–0.600). Conclusion Oral antiviral agents were associated with lower risks of all-cause emergency department visits, hospitalizations, and mortality in non-hospitalized COVID-19 patients aged <60 years.

First-Trimester PLGF and PAPP-A and the Risk of Placenta-Mediated Complications: PREDICTION Prospective Study

ObjectivesTo estimate the association between low first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) and the risk of placenta-mediated complications. MethodsWe performed a secondary analysis of PREDICTION study including nulliparous participants recruited at 11–14 weeks of pregnancy. First-trimester PlGF and PAPP-A were reported in multiples of the median (MoM) adjusted for maternal characteristics and gestational age. Participants were stratified into four groups based on absence/presence of low (<0.4 MoM) PlGF and PAPP-A values. A composite of adverse pregnancy outcomes (including preeclampsia, fetal growth restriction, fetal death, and placental abruption) with delivery before 34, before 37 weeks, and at or after 37 weeks was calculated. ResultsOut of 7262 participants, 86 (1.2%) developed the composite outcome before 37 weeks, including 35 (0.4%) before 34 weeks. The combination of low PAPP-A and low PlGF was associated with the greatest risk of adverse outcomes before 37 weeks (21%) and before 34 weeks (12%) compared to low PlGF alone (7% and 3%), low PAPP-A alone (2% and 1%), or neither marker (1% and 0.4%, respectively, P < 0.001). Looking specifically at pre-term preeclampsia, the combination of low PAPP-A and low PlGF was also associated with a greater risk (12%) compared to low PlGF alone (6%), low PAPP-A alone (0.5%), or neither marker (0.7%, P < 0.001). ConclusionThe combination of low PAPP-A and low PlGF is associated with a very high risk for adverse outcomes before 34 and 37 weeks. An isolated low PAPP-A should not be considered a risk factor for adverse pregnancy outcomes.

Long-term Outcomes of Catheter Ablation Compared to Medical Therapy in Atrial Fibrillation.

The long-term effects of catheter ablation (CA) compared to medical therapy on cardiovascular outcomes for atrial fibrillation (AF) remain undetermined. Using a population-based cohort, we sought to determine what the association between CA as compared to medical therapy was on these outcomes. Using Alberta administrative data, patients with AF as the primary diagnosis during hospitalization, emergency department, or a physician visit were included between October 1, 2008 and March 31, 2018. Based on therapy received, patients were categorized into CA, rate control, or rhythm control with medication. The association of treatment with the primary composite outcome of all-cause death, hospitalization for heart failure or stroke was examined after adjusting for age, sex, comorbidities and baseline medications. Among 39,966 treated AF patients, 2,077 (5.2%), 29,467 (73.7%), 8,422 (21.1%) were treated with CA, rate control, and rhythm control with medication, respectively. Patients in the CA group had a lower incidence of the primary outcome compared (4.0/100 person-years) with rate (8.7/100 person-years) or rhythm control with medication (6.8/100 person-years) group over a median follow-up 6.3 years. In multivariable analysis, compared to CA, both rate (HR: 1.28; 95% CI: 1.09-1.50) and rhythm control with medication (HR: 1.21; 95% CI: 1.03-1.43) were associated with a higher risk of the primary outcome. In this cohort study, patients who received CA demonstrated a reduction in the risk of long-term adverse cardiovascular outcomes compared to medical therapy in patients with AF, providing some data to indicate the effects of CA over the long-term.