Secondary Outcome Analysis Research Articles

Efficacy of Colchicine for Prevention of Stroke and Adverse Cardiovascular Events: A Meta-analysis of 16 Randomized Controlled Trials.

Colchicine has been shown to reduce adverse cardiovascular events (ACE) and stroke among patients with coronary artery disease. However, its efficacy with short- and long-term use and risk of stroke has not been well studied, with conflicting results to date. We sought to evaluate the efficacy of colchicine for the prevention of stroke and other cardiovascular outcomes and to evaluate the effect of short- and long-term use. We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (ORs) were pooled using a random-effect model, and a p value of <0.05 was considered statistically significant. A total of 16 RCTs with 24,967 patients were included (12,538 in colchicine group and 12,429 in the control group) in the analysis. Pooled analysis of primary outcomes showed that risk of incidence of stroke was comparable between colchicine and placebo groups (OR 0.78, 95% confidence interval [CI] 0.59-1.02, p = 0.07). Pooled analysis of secondary outcomes showed that colchicine significantly reduced the risk of incidence of ACE by 33% (OR 0.67, 95% CI 0.54-0.82, p < 0.001), and myocardial infarction by 21% (OR 0.79, 95% CI 0.65-0.95, p = 0.01) compared with placebo. However, the risk of all-cause mortality (OR 0.98, 95% CI 0.79-1.21, p = 0.83) and cardiovascular mortality (OR 0.78, 95% CI 0.56-1.08, p = 0.14) were comparable between both groups of patients. Colchicine was associated with an overall reduction in the risk of incidence of ACE and MI; however, no such effect was observed with mortality and stroke.

The Impact of RNA Interference on Atherosclerotic Plaque Progression: A Meta-Analysis of Preclinical Studies

Background: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of plaque within arteries, remains a leading cause of cardiovascular morbidity and mortality. RNA interference (RNAi) has emerged as a promising therapeutic strategy for atherosclerosis by targeting genes involved in plaque formation and progression. This meta-analysis aimed to evaluate the efficacy of RNAi in preclinical models of atherosclerosis. Methods: A systematic search of PubMed, Embase, and Web of Science databases was conducted from January 2013 to December 2023 to identify preclinical studies investigating the impact of RNAi on atherosclerotic plaque progression. Studies utilizing various RNAi modalities (siRNA, miRNA mimics/inhibitors, shRNA) targeting different genes involved in atherosclerosis were included. The primary outcome was plaque size reduction. Secondary outcomes included changes in plaque composition, lipid profiles, and inflammatory markers. A random-effects model was used to pool data and calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Seven preclinical studies met the inclusion criteria, encompassing a total of 210 animals. RNAi interventions significantly reduced atherosclerotic plaque size compared to controls (SMD -1.51; 95% CI -2.36 to -0.66; p&lt;0.00001; I²=12%). Analysis of secondary outcomes revealed favorable effects of RNAi on plaque composition, with a significant decrease in lipid content and an increase in collagen content. Furthermore, RNAi significantly improved lipid profiles by reducing total cholesterol and LDL-cholesterol levels. A significant reduction in inflammatory markers, such as TNF-α and IL-6, was also observed. Conclusion: This meta-analysis provides compelling evidence supporting the therapeutic potential of RNAi in attenuating atherosclerotic plaque progression in preclinical models. RNAi effectively reduced plaque size, improved plaque stability, and modulated lipid metabolism and inflammation.

Associations Between Sleep Disorders and Treatment Response in Service Members With Post-traumatic Stress Symptoms: A Secondary Outcome Analysis

ABSTRACT Introduction Compared with the civilian population, a higher rate of reported sleep apnea exists among military service members resulting in inadequate sleep. Those who experience chronic sleep deprivation may suffer from debilitating problems that may compromise military mission readiness and unit safety. The purpose of the study on which this secondary outcome analysis was based was to evaluate the effect of manual standardized stress acupuncture as an adjunct therapy to an abbreviated form of cognitive behavioral therapy for insomnia for sleep disturbances in post-deployment service members. The aim of this secondary outcome analysis was 2-fold: (1) to assess the relationship between sleep disorder symptoms and post-traumatic stress symptoms (PSS) and (2) to determine if the presence of sleep disorder symptoms influenced the effects of acupuncture and cognitive behavioral therapy as compared to cognitive behavior therapy only on PSS) in post-deployment military service members. Materials and Methods The study was a 2-arm, single-center, randomized controlled trial approved by the Naval Medical Center San Diego and the Vanderbilt University Institutional Review Board. It was conducted at the U.S. Naval Hospital in Okinawa, Japan. Participants were active duty service members from all military branches who were stationed in Okinawa. Two measures were used to analyze the data: the Global Sleep Assessment Questionnaire (GSAQ) and the Post-traumatic Stress Disorder Checklist. A Pearson correlation coefficient was calculated to determine the relationship between sleep disorder symptoms (i.e., 11 pre-intervention GSAQ symptoms) and PSS treatment outcomes (i.e., PCL and PTSD clusters). Results Results indicated associations between the GSAQ components and PCL total and PTSD cluster scores. Findings showed that the presence of sleep disorder symptoms influenced PSS treatment response in post-deployment military service members. Conclusions Results from this secondary outcome analysis showed associations between GSAQ components (i.e., excessive daytime sleepiness, working conditions causing inadequate sleep, involuntary movements in sleep, and sadness or anxiousness) and PCL total and PTSD cluster scores (i.e., avoidance, negative cognition and mood, avoidance, and hyperarousal). Furthermore, sleep disorder symptoms such as having stressful working conditions (e.g., shift work), probable obstructive sleep apnea, insomnia, anxiety, and depression influenced PSS treatment responses. This study provided information on the major contribution of sleep disorder symptoms in the treatment of PSS through self-report. Future researchers should consider the use of physiologic measures to further understand the mechanisms of how sleep disorder symptoms affect treatment responses in service members with PSS. Implications for this study may assist clinicians in determining effective PSS treatments for those with OSA and insomnia.

Macronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

Background/Objectives: Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. Methods: This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks corrected age) Nutritional intake was analyzed using a 24 h recall at 6 weeks CA and 3-day dietary records at 12 weeks, 6, 9, and 12 months CA. Results: In total, 115 infants were assigned to the early and 82 to the late group. The timing of solid food introduction did not affect macronutrient intake, except for a lower fat and higher carbohydrate intake (% of energy) in the early group at 12 weeks and 6 months CA: early vs. late, fat-12 weeks: 47.0% vs. 49.0%, 6 months: 39.2% vs. 43.3%; carbohydrates-12 weeks: 44.9% vs. 43.2%, 6 months: 51.3% vs. 48.0%. Apart from docosahexaenoic acid (DHA) and arachidonic acid (AA), dietary intake recommendations were met in both groups. While nutrient intakes varied significantly between breastfed and formula-fed infants, those with comorbidities exhibited similar nutrient intake levels compared to those without. Conclusions: Our findings suggest adequate macronutrient intakes in VLBW infants irrespective of the timing of solid introduction. However, there is a notable need to enhance dietary intakes of DHA and AA. Future research is crucial to assess whether current nutrient intakes are sufficient for VLBW infants with comorbidities.

Efficacy of a pharmacist care protocol to manage uncomplicated female cystitis in community pharmacies: an open-label, multicenter, randomized, controlled, cluster study: the PharmaCyst’ protocol

BackgroundUrinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score.MethodsPharmaCyst’ is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student’s t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher’s exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population.DiscussionPharmaCyst’ is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol.Trial registrationThe protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Effects of controlled supramaximal high-intensity interval training on muscle capacities and physical functions for older adults: analysis of secondary outcomes from the Umeå HIT study-a randomised controlled trial.

This study investigated the effectiveness of supramaximal high-intensity interval training (supramaximal HIT) on muscle capacities and physical function compared to moderate-intensity training (MIT) for older adults. Sixty-eight older adults (66-79years, 56% women), not engaged in regular exercise, were randomised to 3months of twice-weekly supramaximal HIT (20minutes including 10 × 6-second intervals) or MIT (40minutes including 3 × 8-minute intervals). Both groups performed the training on stationary bicycles in a group setting. Target intensity was watt-controlled, with standardised cadence and individualised resistance. Outcomes analysed with linear-mixed models included leg power (Nottingham Power Rig), hand grip strength (Jamar dynamometer), static and dynamic balance (One leg stance, 30-second step test), chair stand (30-second chair stand), and anaerobic cycling performance (modified Borg Cycle Strength Test). Baseline values were (supramaximal HIT/MIT, mean ± SD) leg power 198 ± 60/189 ± 53W, hand grip strength 4.2 ± 1.0/4.3 ± 1.1N/kg, static balance 64 ± 41/62 ± 41s, dynamic balance 39 ± 7/38 ± 5 steps, chair stands 22 ± 6/22 ± 6 and anaerobic cycling performance 224 ± 60/217 ± 55W. At 3-month follow-up, a between-group difference in favour of supramaximal HIT [95% CI] was observed in anaerobic cycling performance of 19[3;35] W. Within-group mean changes for supramaximal HIT/MIT were for leg power 8.4[0.9;15.8]/6.0[-1.3;13.3] W, hand grip strength 0.14[0.00;0.27]/0.13[-0.01;0.26] N/kg, static balance 11[3;20]/10[1;18] s, dynamic balance 1.6[0.3;2.8]/2.3[1.1;3.6] steps, 2.1[1.1;3.1]/1.4[0.4;2.3] chair stands and anaerobic cycling performance 31.3[19.6;43.0]/12.0[0.4;23.5] W. Supramaximal HIT showed superior effect on anaerobic cycling performance when compared to MIT. Additionally, the results indicate that supramaximal HIT is comparably beneficial as MIT in terms of effects on muscle capacity and physical function for older adults.

Cardiorespiratory effects of Gamma-Hydroxybutyric Acid (GHB) during isoflurane anaesthesia in pigs

ObjectiveTo investigate the haemodynamic effects of gamma-hydroxybutyric acid (GHB) in isoflurane anaesthetised pigs. Study DesignExperimental, randomized, non-blinded, cross-over study. AnimalsA group of six stress-resistant Landrace pigs (approximately 3 months old; three male, three female; bodyweight 39.2 ± 4 kg (mean ± standard deviation). MethodsAfter premedication (midazolam 0.5 mg kg-1 and ketamine 10 mg kg-1 intramuscularly), and induction [propofol 0.25–0.5 mg kg-1 intravenously IV)], anaesthesia was maintained with isoflurane in oxygen, and either GHB 250 mg kg-1 IV or an equal volume of saline was administered (minimum washout period 1 week). Systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures, heart rate and rhythm, respiratory rate, were recorded every 5 minutes for 2 hours. Arterial samples were collected for blood gas and pharmacokinetic analyses. Relative changes from baseline were calculated and compared between treatments using a mixed model with time, period, and treatment as variables (α < 0.05). ResultsChanges from baseline differed significantly between treatments (p < 0.001) for SAP (GHB -1.6 ± 10.7; saline -5.9 ± 14.8 mmHg), DAP (GHB +2.9 ± 9.6; saline -6.5 ± 10.7 mmHg) and MAP (GHB +2.2 ± 10.5; saline -5.7 ± 9.6 mmHg). Statistical analysis of secondary outcomes suggested effects on PaO2 (GHB -45.2 ± 29.8 mmHg [-6.03 ± 3.97 kPa]; saline +24.5 ± 32.4 mmHg [+3.27 ± 4.32 kPa]; p < 0.001) and PaCO2 (GHB -2 ± 10 mmHg [-0.27 ± 1.33 kPa]; saline -9 ± 8 mmHg [-1.20 ± 1.07 kPa]; p < 0.001). Mean maximum plasma concentration of GHB was 1171.1 ± 229.3 μg mL-1, with volume of distribution 335.3 ± 68.5 mL kg-1, clearance 77.2 ± 19.12 mL kg-1 hour-1 and elimination half-life 3.10 ± 0.80 hours. Conclusions and clinical relevanceGHB did not cause severe physiological side effects and may reduce cardiovascular depression.

A custom tailored, evidence-based, theory-informed intervention for healthcare professionals to prevent burnout (LAGOM): study protocol for a pragmatic randomized controlled trial

BackgroundHealthcare professionals in hospitals are exposed to a high level of professional stress, time pressure, workload, and often times poor organizational support. This makes them especially susceptible to burnout. In this pragmatic randomized controlled trial, we test the hypothesis that participation in a 9-week program (LAGOM) that was designed in close collaboration with healthcare professionals, incorporating both individual and organizational aspects reduces emotional exhaustion in healthcare professionals (primary outcome).MethodsEighty four nurses and physicians working at the Charité – Universitätsmedizin Berlin and the Immanuel Hospital Berlin are automatically randomized to the LAGOM program (n = 42) or to usual care (n = 42) in a one-to-one allocation rate. The primary outcome emotional exhaustion is measured by the Maslach Burnout Inventory—Human Services Survey at baseline, post-intervention, and 1-month follow-up via an online survey. Secondary outcomes include depersonalization, personal accomplishment, subjective stress, mental well-being, self-care, self-efficacy, working conditions, mindfulness, and adverse events. Electrophysiological measures for heart rate variation analysis are captured. The PRECIS-2 tool is used to characterize the degree of pragmatism in our trial. Data analysis and primary intention-to-treat analysis using repeated measures analysis of variance are performed blind to intervention allocation. Per-protocol, subgroup, and secondary outcome analyses are conducted exploratively. An advisory board consisting of various stakeholders accompanies the study process.DiscussionIf LAGOM proves to be effective in reducing symptoms of burnout, the program could make an important contribution to tackling the problem of the very high burnout rates among healthcare professionals and become an integral part of preventive services offered by hospitals.Trial registrationGerman Clinical Trials Register, DRKS00034060. Registered 31 May 2024.

Micronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

Background/Objectives: The complementary feeding period is crucial for addressing micronutrient imbalances, particularly in very low birth weight (VLBW) infants. However, the impact of the timing of solid food introduction on micronutrient intake in a representative VLBW population remains unclear. Methods: This prospective, observational study investigated micronutrient intake during complementary feeding in VLBW infants categorized based on whether solids were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks CA). Nutritional intake was assessed using a 24 h recall at 6 weeks CA and with 3-day dietary records at 12 weeks and at 6, 9, and 12 months CA. Results: Among 218 infants, 115 were assigned to the early group and 82 to the late group. In total, 114-170 dietary records were valid for the final analysis at each timepoint. The timepoint of solid introduction did not affect micronutrient intake, except for a higher iron and phosphorus intake at 6 months CA in the early group (early vs. late: iron 0.71 vs. 0.58 mg/kg/d, adjusted p-value (p-adj.) = 0.04; phosphorus 341 vs. 286 mg/d, p-adj. = 0.04). Total vitamin D, calcium, zinc, and phosphorus greatly met intake recommendations; however, dietary iron intake was insufficient to equalize the iron quantity from supplements during the second half year CA. While nutrient intakes were similar between infants with and without comorbidities, breastfed infants had lower micronutrient intakes compared with formula-fed infants. Conclusions: This study suggests that micronutrient intakes were sufficient during complementary feeding in VLBW infants. However, prolonged iron supplementation may be necessary beyond the introduction of iron-rich solids. Further research is essential to determine micronutrient requirements for infants with comorbidities.

Acetylsalicylic acid alone or in combination with either enoxaparin or unfractionated heparin for postoperative thromboprophylaxis in coronary artery bypass surgery patients. A randomised clinical trial assessing surrogate outcomes

IntroductionCoronary artery bypass graft surgery has considerable effects on patient haemostasis. Heparins as thromboprophylaxis may be beneficial but may also increase the risk of bleeding complications. ObjectivesTo assess the effects of heparins on haemostasis in post-coronary artery bypass graft patients. MethodsAcross one year, we randomised 60 participants scheduled for an elective coronary artery bypass graft-procedure with or without aortic valve replacement. The trial was a prospective, open-label (though blinded for the laboratory), randomised, single-centre trial with three intervention groups (n = 20 in each): group 1 received acetylsalicylic acid, group 2 received subcutaneous low molecular weight heparin and acetylsalicylic acid, and group 3 received intravenous unfractionated heparin and acetylsalicylic acid. Primary outcomes were platelet activation (Multiplate® ASPI-test) and time to clot initiation (TEG® R-time). We secondly assessed several additional Multiplate® and TEG® parameters. ResultsGroup 3 (intravenous unfractionated heparin) compared with group 1 (acetylsalicylic acid alone) showed evidence of 1) increased clot initiation time (R-time + 0.9 min; 95 % CI: +0.4 to +1.4 min; P = 0.009), and 2) decreased 30-min lysis (−1.3 %; 95 % CI: −2.1 to −0.5 %; P = 0.02). The remaining analyses of primary and secondary outcomes showed no evidence of a difference between the three groups. DiscussionIntravenous unfractionated heparins may increase the clot initiation time post-operatively after coronary artery bypass graft surgery and reduce lysis. Otherwise, there seems to be no effect of low molecular weight or unfractionated heparin on haemostatic parameters after coronary artery bypass surgery patients.

Effect of zoledronic acid and pamidronate on renal function.

There is limited data on the effect bisphosphonates have on renal function and the use of bisphosphonates in patients with baseline renal dysfunction. The purpose of this study was to determine the incidence of acute kidney injury (AKI) in patients after receiving zoledronic acid or pamidronate. A retrospective cohort analysis was conducted of patients who received one dose of a bisphosphonate, either zoledronic acid or pamidronate. The primary objective of this study was to determine the incidence of AKI after bisphosphonate administration. Baseline characteristics were compared, and unadjusted analyses of primary and secondary outcomes were completed using Pearson's chi-square or Fisher's exact test for categorical data and Mann-Whitney U test for continuous data. There was no difference found in AKI incidence between zoledronic acid and pamidronate (17.1% vs. 15.0%; p = 1.00). Additionally, there was no difference found in AKI incidence between patients with baseline renal dysfunction and those without, (25.0% vs. 15.0%; p = 0.322). There were no differences observed in either corrected calcium within seven days or serum creatinine (SCr) within 30 days returning to baseline after administration, nor were there differences in fever or hypophosphatemia incidences. Bisphosphonates may be used to treat hypercalcemia of malignancy in patients with and without renal dysfunction. AKI may occur post infusion; however, long-term effects on renal function are infrequent when hydrating patients prior to administration and adhering to the manufacturer's recommended infusion rate.

Effects on patient activation of eHealth support in addition to standard care in patients after radical prostatectomy: Analysis of secondary outcome from a randomized controlled trial.

Prostate cancer is often treated with radical prostatectomy, but surgery can leave patients with side effects. Patients who actively take part in their rehabilitation have been shown to achieve better clinical outcomes. eHealth support has the potential to increase patient activation, but has rarely been evaluated in long-term randomized controlled trials. Therefore, we evaluated the effects on patient activation of eHealth support (electronic Patient Activation in Treatment at Home, ePATH) based on motivational theory. The aim was to investigate the effects of eHealth support on patient activation at 6 and 12 months after radical prostatectomy, compared with standard care alone, and associations with baseline patient activation and depression. A multicentre randomized controlled trial with two study arms was conducted. Men planned for radical prostatectomy at three county hospitals in southern Sweden were included and randomized to the intervention or control group. The effects of ePATH on the secondary outcome, patient activation, were evaluated for one year after surgery using the patient activation measure and analysed using a linear mixed model. The study included 170 men during 2018-2019. In the intervention group, 64% (53/83) used ePATH. The linear mixed model showed no significant differences between groups in patient activation [β -2.32, P .39; CI -7.64-3.00]. Baseline patient activation [β 0.65, P < .001; CI 0.40-0.91] and depression [β -0.86, P .03; CI -1.64- -0.07] statistically impacted patient activation scores over one year. ePATH had no impact on patient activation during long-term prostate cancer rehabilitation. However, patient activation at baseline and depression scores significantly influenced patient activation, underlining the need to assess these aspects in prostate cancer surgery rehabilitation. ISRCTN Registry ISRCTN18055968, (07/06/2018); https://www.isrctn.com/ISRCTN18055968; International Registered Report Identifier: RR2-10.2196/11625.

Phenobarbital as an adjunctive agent for sedation in pediatric intensive care unit patients: A single-center, retrospective study from Colorado

Abstract Background: Pediatric patients require pharmacological management of pain and agitation associated with mechanical ventilation. Pain and agitation may be refractory to opioids and alpha-2 agonists, prompting the use of adjunctive analgesics and sedatives with alternative mechanisms. The purpose of this study was to describe the use of phenobarbital as an adjunctive agent for refractory agitation in critically ill, mechanically ventilated pediatric patients. Subjects and Methods: This was a single-center, retrospective chart review at a pediatric intensive care unit (PICU) at a pediatric academic medical center in America between 2016 and 2021. Children aged 2 months to 18 years old were admitted to the PICU were mechanically ventilated and received phenobarbital for adjunct sedation. Sixty-three patients had phenobarbital dosing data evaluated, and the 38 patients who were not receiving continuous neuromuscular blockade were included in the primary and secondary outcome analysis of time within the goal sedation score. Descriptive statistics was used to assess baseline characteristics and the primary outcome. Wilcoxon signed-rank tests were used to evaluate secondary outcomes. Results: Patients spent significantly more time within the goal sedation score range after phenobarbital compared to before phenobarbital. The median number of rescue sedative boluses, morphine equivalents (MEs), and benzodiazepine equivalents (BZDE) significantly decreased 2 days after the first phenobarbital dose compared to the 2 days before the first phenobarbital dose. Conclusions: The use of phenobarbital as an adjunct sedative was associated with a statistically significant increase in time spent in the goal sedation score range and decrease in ME, BZDE, and concomitant sedative boluses.

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Association between different diet quality scores and depression risk: the REGICOR population-based cohort study

BackgroundOur aim was to determine the association between diet quality and depression incidence in the population-based REGICOR cohort study, Catalonia, Spain.MethodsProspective observational study using participants’ baseline (2003–2006), follow-up (2007–2013) and clinical records data. Five diet quality scores were derived from a food frequency questionnaire (FFQ) at baseline: the relative Mediterranean Diet Score (rMED), the Modified Mediterranean Diet Score (ModMDS), a Dietary Approaches to Stop Hypertension (DASH) score, a Healthful Plant-based Diet Index (HPDI) and the World Health Organization Healthy Diet Indicator (WHO-HDI). Participants using pharmacological antidepressant treatment were excluded as a proxy for presence of depression at baseline. At follow-up, the Patient Health Questionnaire (PHQ-9) was applied to assess depressive symptoms (≥ 10 defining depressive disorder). A secondary outcome was depression diagnosis assessed through clinical records. Logistic regression and Cox proportional hazards models were used.ResultsMain analysis included 3046 adults (50.3% women) with a mean age of 54.7 (SD = 11.6) years. After 6-years follow-up, 184 (6.04%) cases of depressive disorder were identified. There was 16% lower odds of depressive disorder per 1SD increase of rMED (OR = 0.84; 95%CI = 0.71–0.98). Secondary outcome analysis (n = 4789) identified 261 (5.45%) incident cases of clinical depression diagnosis over 12 years follow-up, and 19% lower risk of clinical depression was observed with the WHO-HDI (HR = 0.81; 95%CI = 0.70–0.93). Adjusting for BMI did not attenuate the findings.ConclusionsA significant inverse association between diet quality and depression incidence was found in this population-based cohort study, independent of sociodemographic, health and lifestyle. Adherence to a healthy diet could be a complementary intervention for the prevention of depression.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Effects of Interrupting Prolonged Sitting with Light-Intensity Physical Activity on Inflammatory and Cardiometabolic Risk Markers in Young Adults with Overweight and Obesity: Secondary Outcome Analyses of the SED-ACT Randomized Controlled Crossover Trial.

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m2, glycated hemoglobin A1C (HbA1c) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T0), 1 h after lunch (T1) and 8 h after baseline (T2). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 (p = 0.014), TG (p = 0.012), TC (p = 0.017), HDL-C (p = 0.020), LDL-C (p = 0.021), albumin (p = 0.003), total protein (p = 0.021), and uric acid (p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP (p = 0.529), creatinine (p = 0.199), TyG (p = 0.331), and the lipid ratios TG/HDL-C (p = 0.793) and TC/HDL-C (p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity.

Machine Learning Prediction of Autism Spectrum Disorder From a Minimal Set of Medical and Background Information

Early identification of the likelihood of autism spectrum disorder (ASD) using minimal information is crucial for early diagnosis and intervention, which can affect developmental outcomes. To develop and validate a machine learning (ML) model for predicting ASD using a minimal set of features from background and medical information and to evaluate the predictors and the utility of the ML model. For this diagnostic study, a retrospective analysis of the Simons Foundation Powering Autism Research for Knowledge (SPARK) database, version 8 (released June 6, 2022), was conducted, including data from 30 660 participants after adjustments for missing values and class imbalances (15 330 with ASD and 15 330 without ASD). The SPARK database contains participants recruited from 31 university-affiliated research clinicals and online in 26 states in the US. All individuals with a professional ASD diagnosis and their families were eligible to participate. The model performance was validated on independent datasets from SPARK, version 10 (released July 21, 2023), and the Simons Simplex Collection (SSC), consisting of 14 790 participants, followed by phenotypic associations. Twenty-eight basic medical screening and background history items present before 24 months of age. Generalizable ML prediction models were developed for detecting ASD using 4 algorithms (logistic regression, decision tree, random forest, and eXtreme Gradient Boosting [XGBoost]). Performance metrics included accuracy, area under the receiver operating characteristics curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and F1 score, offering a comprehensive assessment of the predictive accuracy of the model. Explainable AI methods were applied to determine the effect of individual features in predicting ASD as secondary outcomes, enhancing the interpretability of the best-performing model. The secondary outcome analyses were further complemented by examining differences in various phenotypic measures using nonparametric statistical methods, providing insights into the ability of the model to differentiate between different presentations of ASD. The study included 19 477 (63.5%) male and 11 183 (36.5%) female participants (mean [SD] age, 106 [62] months). The mean (SD) age was 113 (68) months for the ASD group and 100 (55) months for the non-ASD group. The XGBoost (termed AutMedAI) model demonstrated strong performance with an AUROC score of 0.895, sensitivity of 0.805, specificity of 0.829, and PPV of 0.897. Developmental milestones and eating behavior were the most important predictors. Validation on independent cohorts showed an AUROC of 0.790, indicating good generalizability. In this diagnostic study of ML prediction of ASD, robust model performance was observed to identify autistic individuals with more symptoms and lower cognitive levels. The robustness and ML model generalizability results are promising for further validation and use in clinical and population settings.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

Comparative Efficacy of Biologics and Small Molecule Therapies in Improving Patient-Reported Outcomes in Ulcerative Colitis: Systematic Review and Network Meta-Analysis

Abstract Background Ulcerative colitis (UC) is a chronic disorder with a considerable negative impact on health-related quality of life (HRQoL), which has been recently recognized as an important treatment target. The purpose of this study is to compare the efficacy of different biologics and small molecule therapies in achieving better patient-reported outcomes and HRQoL in patients with UC. Methods We performed a systematic review and network meta-analysis of the EMBASE, MEDLINE, and Cochrane Central databases from inception until February 1, 2024. The primary endpoint was clinical remission in the patient-reported outcome (PRO-2) score in UC patients who were treated with different biologics or small molecules during induction and maintenance phases. PRO-2 score is the sum of both stool frequency and rectal bleeding subscores. The secondary outcome was improvement of HRQoL defined as an increase in Inflammatory Bowel Disease Questionnaire score of ≥16 points from baseline or any change in total score from baseline. A random effects model was used, and outcomes were reported as odds ratio with 95% confidence interval. Interventions were ranked per the SUCRA (surface under the cumulative ranking curve) score. Results A total of 54 studies were included in the primary outcome analysis and 15 studies were included in the secondary outcome analysis. The primary analysis showed that during the induction phase all of included drugs were better than placebo in improving the PRO-2 score. Interestingly, upadacitinib was found to be superior to most medications in improving PRO-2 scores. The secondary analysis showed that guselkumab ranked first in the improvement of the Inflammatory Bowel Disease Questionnaire score, followed by upadacitinib during the induction phase. Conclusion Upadacitinib ranked first in PRO-2 clinical remission during the induction and maintenance phases. Guselkumab, mirikizumab, tofacitinib, and upadacitinib were the only novel medications that were superior to placebo in improving HRQoL in UC, with guselkumab ranking the highest, followed by tofacitinib and upadacitinib. During maintenance of remission, tofacitinib ranked highest in improving HRQoL.