Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions: A Systematic Review and Meta-Analyses.

BACKGROUND: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney outcomes in patients with varying combinations of heart failure, chronic kidney disease, and type 2 diabetes mellitus have not been quantified. METHODS: PubMed and Scopus were queried up to December 2023 for primary and secondary analysis of placebo-controlled trials of SGLT2i in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus. Outcomes of interest were composite kidney endpoint (combination of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, sustained doubling of serum creatinine, varying percent change in eGFR, and need for kidney replacement therapy), rate of eGFR slope decline and albuminuria progression. Hazard ratios (HR) and mean differences with their 95% confidence intervals (CI) were extracted onto an excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). RESULTS: Eleven trials (n=80,928 patients) were included. Compared with the placebo, SGLT2i reduced the risk of the composite kidney endpoint by 41% (hazard ratio 0.59; 95%CI 0.42-0.83) in heart failure with reduced ejection fraction, 36% (hazard ratio 0.64;95%CI 0.55-0.73) in chronic kidney disease, and 38% (hazard ratio 0.62;95%CI 0.56-0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities, as well as patients without baseline heart failure, chronic kidney disease, or type 2 diabetes mellitus. SGLT2i slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (hazard ratio 0.64; 95%CI 0.56-0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. CONCLUSIONS: SGLT2i improved kidney outcomes in cohorts with heart failure, chronic kidney disease, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.

Role of telemedicine in the management of obesity: State-of-the-art review.

Obesity is a worsening public health epidemic that remains challenging to manage. Obesity substantially increases the risk of cardiovascular diseases and presents a significant financial burden on the healthcare system. Digital health interventions, specifically telemedicine, may offer an attractive and viable solution for managing obesity. During the COVID-19 pandemic, the need for a safer alternative to in-person visits led to the increased popularity of telemedicine. Multiple studies have tested the efficacy of telemedicine modalities, including digital coaching via videoconferencing sessions, e-health monitoring using wearable devices, and asynchronous forms of communication such as online chatrooms with counselors. In this review, we discuss the available evidence for telemedicine interventions in managing obesity, review current challenges and barriers to using telemedicine, and outline future directions to optimize the management of patients with obesity using telemedicine.

Association of low diastolic blood pressure with cardiovascular outcomes and all-cause mortality: A meta-analysis.

BACKGROUND: Reduction of diastolic blood pressure (DBP) below 70 mmHg may decrease perfusion to the heart and worsen cardiovascular (CV) outcomes. AIMS: Explore the association between low DBP and CV outcomes. METHODS: We searched the online databases until August 2023 for studies reporting the risk of all-cause mortality (ACM) or CV outcomes in patients with low versus normal DBP (70-80mm Hg). RESULTS: Inclusion of 10 studies (n = 1,998,223 patients) found that a mean achieved DBP < 60 mmHg was associated with an increased risk of all-cause mortality (HR 1.48; 95 % CI [1.26-1.74]), especially in patients with pre-existing CV disease. It was also associated to a higher risk of major adverse cardiovascular events (HR 1.84; [1.28-2.65]) and myocardial infarction (HR 1.49; [1.13-1.97]). A DBP of 60-69 mmHg was associated with an increased risk of all-cause mortality (HR 1.11; [1.03-1.20]). CONCLUSION: Reduction of DBP, particularly below 60 mmHg, is associated with increased risk of ACM.

Clinical Outcomes in Hypertensive Emergency: A Systematic Review and Meta-Analysis.

Background To study the prevalence and types of hypertension-mediated organ damage and the prognosis of patients presenting to the emergency department (ED) with hypertensive emergencies. Methods and Results PubMed was queried from inception through November 30, 2021. Studies were included if they reported the prevalence or prognosis of hypertensive emergencies in patients presenting to the ED. Studies reporting data on hypertensive emergencies in other departments were excluded. The extracted data were arcsine transformed and pooled using a random-effects model. Fifteen studies (n=4370 patients) were included. Pooled analysis demonstrates that the prevalence of hypertensive emergencies was 0.5% (95% CI, 0.40%-0.70%) in all patients presenting to ED and 35.9% (95% CI, 26.7%-45.5%) among patients presenting in ED with hypertensive crisis. Ischemic stroke (28.1% [95% CI, 18.7%-38.6%]) was the most prevalent hypertension-mediated organ damage, followed by pulmonary edema/acute heart failure (24.1% [95% CI, 19.0%-29.7%]), hemorrhagic stroke (14.6% [95% CI, 9.9%-20.0%]), acute coronary syndrome (10.8% [95% CI, 7.3%-14.8%]), renal failure (8.0% [95% CI, 2.9%-15.5%]), subarachnoid hemorrhage (6.9% [95% CI, 3.9%-10.7%]), encephalopathy (6.1% [95% CI, 1.9%-12.4%]), and the least prevalent was aortic dissection (1.8% [95% CI, 1.1%-2.8%]). Prevalence of in-hospital mortality among patients with hypertensive emergency was 9.9% (95% CI, 1.4%-24.6%). Conclusions Our findings demonstrate a pattern of hypertension-mediated organ damage primarily affecting the brain and heart, substantial cardiovascular renal morbidity and mortality, as well as subsequent hospitalization in patients with hypertensive emergencies presenting to the ED.

An Individual Patient-Level Meta-Analysis of Ischemic Versus Nonischemic Cardiomyopathy and Trajectory of Decongestion in Patients With Acute Decompensated Heart Failure.

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.

Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations.

BACKGROUND: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on heart failure (HF) outcomes and cardiovascular (CV) death in patients with varying combinations of type 2 diabetes mellitus (T2DM), HF, and chronic kidney disease (CKD) are uncertain. OBJECTIVES: The authors conducted a meta-analysis assessing the effects of SGLT2 inhibitors on HF outcomes and CV death across different patient populations. METHODS: Online databases were queried up to November 2022 for primary and secondary analyses of trials of SGLT2 inhibitors in patients with HF, T2DM, or CKD. Outcomes of interest were composite of first heart failure hospitalization (HFH) or CV death (first HFH/CV death), first HFH, and CV death. Data were pooled by means of a random-effects model to derive HRs and 95% CIs. RESULTS: Thirteen trials (n = 90,413) were included. Compared with placebo, SGLT2 inhibitors reduced the risk of first HFH/CV death by 24% in HF (HR: 0.76; 95% CI: 0.72-0.81), 23% in T2DM (HR: 0.77; 95% CI: 0.73-0.81), and 23% in CKD (HR: 0.77; 95% CI: 0.72-0.82). The benefit was consistent in HF with reduced or preserved ejection fraction, HF with or without T2DM, and HF with or without CKD. The benefit was also consistent in T2DM with or without CKD, T2DM without HF, CKD without HF, and in patients with all 3 comorbidities. SGLT2 inhibitors significantly reduced CV death by 16% in HF, 15% in T2DM, and 12% in CKD. CONCLUSIONS: SGLT2 inhibitors reduce HF events and CV death in cohorts of HF, T2DM and CKD, and these effects appear consistent in patients with varying combinations of these diseases.

Effect of vitamin D on postoperative atrial fibrillation in patients who underwent coronary artery bypass grafting: A systematic review and meta-analysis.

BACKGROUND: Vitamin D insufficiency/deficiency has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). This is associated with significantly increased morbidity and mortality leading to not only prolonged hospital and intensive care unit (ICU) stay, but increased risk of stroke, heart failure, dementia, and long-term atrial fibrillation. This analysis aims to evaluate the efficacy of vitamin D supplementation in preventing POAF in patients undergoing CABG. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to June 2022 for randomized controlled trials (RCTs). The outcome of interest was the incidence of POAF. Secondarily, we analyzed the length of ICU stay, length of hospital stay, cardiac arrest, cardiac tamponade, and blood transfusion. Results were pooled using a random-effect model. Three RCTs consisting of 448 patients were included. RESULTS: Our results suggest that vitamin D significantly reduced the incidence of POAF (RR: 0.60; 95 % CI: 0.40, 0.90; p = 0.01; I2 = 8 %). It was also observed that vitamin D significantly reduced the duration of ICU stay (WMD: -1.639; 95 % CI: -1.857, -1.420; p < 0.00001). Furthermore, the length of hospital stay (WMD: -0.85; 95 % CI: -2.14, 0.43; p = 0.19; I2 = 87 %) was also reduced, however, the result was not significant. CONCLUSION: Our pooled analysis suggests that vitamin D prevents POAF. Future large-scale randomized trials are needed to confirm our results.

Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories.

BACKGROUND: Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction. OBJECTIVES: The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively). METHODS: A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. RESULTS: In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved. CONCLUSIONS: The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.

Association of Electronic Cigarette Exposure on Cardiovascular Health: A Systematic Review and Meta-Analysis.

Despite the growing use of electronic cigarettes (EC) in the Unites States, particularly among young people, and their perceived safety, current evidence suggests that EC usage may cause adverse clinical cardiovascular effects. Therefore, we aim to pool all studies evaluating the association of EC exposure with cardiovascular health. Medline, Cochrane CENTRAL, and Scopus were searched for studies from January 1, 2006 until December 31, 2022. Randomized and observational studies reporting cardiovascular outcomes, hemodynamic parameters, and biomarkers of platelet physiology, before and after acute or chronic EC exposure were pooled using a random-effects model. Overall, 27 studies (n = 863) were included. Heart rate increased significantly after acute EC exposure (weighted mean difference [WMD]: 0.76 bpm; 95% confidence interval [CI], 0.48, 1.03; P < 0.00001; I2 = 92%). Significant increases in systolic blood pressure (WMD: 0.28 mmHg; 95% CI, 0.06, 0.51; P = 0.01; I2 = 94%), diastolic blood pressure (WMD: 0.38 mmHg; 95% CI, 0.16, 0.60; P = 0.0006; I2 = 90%), and PWV (WMD: 0.38; 95% CI, 0.13, 0.63; P = 0.003; I2 = 100%) were also observed. Augmentation index increased significantly (SMD: 0.39; 95% CI, 0.11, 0.67; P = 0.007; I2 = 90%), whereas reduction in flow-mediated dilation (WMD: -1.48; 95% CI, -2.49, -0.47; P = 0.004; I2 = 45%) was observed. Moreover, significant rise in both soluble P-selectin (WMD: 4.73; 95% CI, 0.80, 8.66; P = 0.02; I2 = 98%) and CD40L (WMD: 1.14; 95% CI, 0.41, 1.87; P = 0.002; I2 = 79%) was observed. Our results demonstrate that smoking EC is associated with a significant increase in cardiovascular hemodynamic measures and biomarkers. Our findings can aid policymakers in making informed decisions regarding the regulation of EC to ensure public safety.

High-Intensity Interval Training Versus Moderate Continuous Training in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

High-intensity interval training (HIIT) is a novel training approach that improves cardiopulmonary fitness and functional capacity in numerous chronic conditions, however its impact in patients with heart failure (HF) with preserved ejection fraction (HFpEF) is uncertain. We evaluated data from prior studies reporting the effects of HIIT versus moderate continuous training (MCT), on cardiopulmonary exercise outcomes in patients with HFpEF. PubMed and SCOPUS were queried from inception till February 1st, 2022 for all randomized controlled trials (RCT) comparing the effect of HIIT versus MCT in patients with HFpEF on peak oxygen consumption (peak VO2), left atrial volume index (LAVI), respiratory exchange ratio (RER), and ventilatory efficiency (VE/CO2 slope). A random-effects model was applied, and the weighted mean difference (WMD) of each outcome was reported with 95% confidence intervals (CI). Three RCTs (total N = 150 patients with HFpEF), with a follow-up of 4 to 52 weeks were included in our analysis. Our pooled analysis demonstrated that HIIT significantly improved peak VO2 (WMD = 1.46 mL/kg/min (0.88, 2.05); P < 0.00001; I2 = 0%), as compared to MCT. However, no statistically significant change was demonstrated for LAVI (WMD = -1.71 mL/m2 (-5.58, 2.17); P = 0.39; I2 = 22%), RER (WMD = -0.10 (-0.32, 0.12); P = 0.38; I2 = 0%), and VE/CO2 slope (WMD = 0.62 (-1.99, 3.24); P = 0.64; I2 = 67%) in patients with HFpEF. Across current RCT data, HIIT, compared to MCT, had a significant impact on improving peak VO2. Conversely, there was no significant change in LAVI, RER, and VE/CO2 slope between HFpEF patients undertaking HIIT as opposed to MCT.

Health status across major subgroups of patients with heart failure and preserved ejection fraction.

AIMS: There are limited data on health status and changes in it over time across major subgroups of patients with heart failure and preserved ejection fraction (HFpEF), including ejection fraction spectrum, age, sex, region, body mass index (BMI), and comorbidities including diabetes, chronic kidney disease (CKD), anaemia, and atrial fibrillation/flutter. METHODS AND RESULTS: In the EMPEROR-Preserved trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was assessed at baseline, 12, 32 and 52 weeks. Determinants of baseline KCCQ score and change over time, and the impact of empagliflozin on KCCQ scores were studied in specified subgroups. A Cox model was used to assess the association between 5- and 10-point increase and 5-point decrease in KCCQ score from baseline to week 12 and later outcomes. Among 2979 participants in the placebo arm, mean KCCQ clinical summary score (CSS) was 70.7 (20.8). Older age, female sex, BMI, anaemia, and a history of diabetes, and CKD were associated with worse scores. KCCQ-CSS score improved during follow-up; patients with atrial fibrillation/flutter at enrollment (p trend = 0.014) and CKD (p trend < 0.001) had less improvement. A 5-point increase in KCCQ-CSS at week 12 was associated with lower risk of cardiovascular death or heart failure hospitalization (5%), cardiovascular death (8%), and first heart failure hospitalization (4%) subsequently. A similar trend was seen with KCCQ total symptom score (TSS) and overall summary score (OSS). Empagliflozin improved KCCQ-CSS, -TSS and -OSS scores similarly across subgroups studied except for greater improvement in patients with the highest BMI (p trend = 0.153, 0.08 and 0.078, respectively). CONCLUSION: Health status in patients with HFpEF is impaired, especially in elderly, women, and those with obesity and comorbidities. Empagliflozin improved health status among all key subgroups studied with a greater effect in obese patients.

Remote Monitoring in Heart Failure patients: A Systemic Review and Meta-analysis.

Heart failure (HF) approximately affects about 1%-2% of the adult population in developed countries and is a leading cause of morbidity and mortality worldwide. Inadequate HF management occurs because of poor adherence to prescribed medications. This meta-analysis compares and contrasts standard care with remote medication monitoring in HF patients. Six randomized control trials were selected using the PubMed database from inception until October 25, 2022, incorporating a total of 2390 patients with HF, out of which 1260 were subjected to remote monitoring while the remaining were in the control group. An odds ratio (OR) with a confidence interval (CI) of 95% was calculated. Remote monitoring in HF patients did not significantly reduce the risks of Cardiovascular (CV) hospitalization <6 months (RR = 0.32, P = 0.27), emergency department (ED) visits (RR = 0.95, P = 0.56) and all-cause mortality (RR = 1.08, P = 0.36). However, a significant reduction in CV hospitalization >6 months was associated with remote monitoring (RR = 0.83, P = 0.002). The meta-analysis revealed that remote monitoring does not significantly reduce the risks of CV hospitalizations, ED visits, or mortality in patients with HF. Therefore, standard care methods must continue to be utilized in HF management.

Trajectory of Decongestion and Mortality in Young Adults with Acute Heart Failure.

Although the prevalence of HF in young adults (age <50 years) is increasing, there are limited data on the trajectory of decongestion and short-term outcomes in young adults with acute heart failure (AHF). We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network (the Diuretic Optimization Strategies trial, the Renal Optimization Strategies Trial, and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The association between young age (<50 years and >50 years) and in-hospital changes in various measures of decongestion as well as short-term outcomes including risk for rehospitalization, and all-cause mortality was evaluated. Of 762 patients, 72 (10.3%) patients were young. Young adults were more likely to be African American (53.8% vs 19.3%), to have a lower rate of ischemic HF etiology (25.6% vs 60.4%, P <0.001), and a lower burden of hypertension, chronic kidney disease and atrial fibrillation. Young adults had a lower left ventricular ejection fraction (median 20% vs 33%, P < 0.001); they had a higher admission weight (median 242.7 lbs vs 201.5 lbs, P < 0.001), but lower NT-pro BNP levels (median 3622 pg/mL vs 4676 pg/mL, P = 0.003). After covariate adjustment, there was no difference in the change in NT-pro BNP (P = 0.25), net fluid loss (P = 0.42), or renal function (P = 0.56) between young and older adults by 72 or 96 hours of randomization. There was no difference in orthodema congestion score or the composite clinical endpoint during the follow-up (all-cause mortality or any rehospitalization) (adjusted odds ratios (95% confidence intervals): 2.51 (0.78-8.01), P = 0.12). In this pooled analysis of 3 clinical trial cohorts, compared with older adults, younger adults had a unique demographic and clinical profile. Despite these differences, there was no difference by age group in in-hospital decongestion or post-discharge readmission or mortality.

Is it safe and effective to administer COVID-19 vaccines during pregnancy? A systematic review and meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of COVID-19 vaccines in pregnant women performing an updated meta-analysis. METHODS: We searched PubMed, Cochrane Central, and SCOPUS from inception to March 2022. Outcomes of interest were incidence of adverse maternal, fetal and neonatal consequences pertaining to safety of the vaccines. Secondarily, we analyzed the number of SARS-CoV-2 infections, hospitalization for COVID-19, and admission to the I.C.U. for COVID-19 assessing the effectiveness of vaccines. Results were pooled using a random effects model. RESULTS: Ten observational studies (n=326,499) analyzing pregnant women were included. Our results suggest that COVID-19 vaccination prevents infection (OR: 0.56, 95% CI: 0.47, 0.67; P = <0.00001) and related hospitalizations (OR: 0.50, 95% CI: 0.31, 0.82; P = 0.006) effectively. It was also observed that vaccination does not change adverse outcomes in pregnancy, namely preeclampsia or eclampsia, stroke (four weeks of delivery), meconium-stained amniotic fluid, spontaneous vaginal delivery, operative vaginal delivery, cesarean delivery, postpartum hemorrhage, and blood transfusions. Furthermore, the vaccine was observed to be protective against neonatal COVID-19 I.C.U. admissions (OR: 0.85; 95% CI: 0.81, 0.90; P = <0.00001). CONCLUSION: Our pooled analysis suggests that the COVID-19 vaccination in pregnant women prevents infection effectively and has no adverse outcomes. Future large-scale trials in a randomized fashion are needed to confirm our results.

Inconsistent Outcome Reporting in Heart Failure Randomized Controlled Trials.

BACKGROUND: Randomized controlled trials (RCTs) may report outcomes different from those prespecified on trial-registration websites, protocols and statistical analysis plans (SAPs). This study sought to investigate the prevalence and characteristics of heart failure (HF) RCTs that report outcomes different from those prespecified. METHODS AND RESULTS: MEDLINE via PubMed was searched to include phase II-IV HF RCTs in 9 high-impact journals from 2010 to 2020. Outcomes reported in trial publications were compared with prespecified outcomes in protocols, registration websites and SAPs. We used the χ2 or Fisher exact test to analyze correlations between trial characteristics and inconsistencies. Among 216 trials, 32 inconsistencies were observed in 28 trials (13.0%). Among 32 inconsistencies, 2 (6.3%) pertained to omission of prespecified primary outcomes, 4 (12.5%) to omission of prespecified secondary outcomes, 2 (6.3%) to changing prespecified primary outcomes to secondary outcomes, and 2 (6.3%) to changing prespecified secondary outcomes to primary outcomes. Of the inconsistencies, 3 (9.4%) pertained to addition of new primary outcomes, 17 (53.1%) to addition of new secondary outcomes, and 2 (6.3%,) to changes in the timing of assessment of primary outcomes. The majority of the inconsistencies favored statistically significant findings; 78 (36.1%) were registered retrospectively. Single-center recruitment was associated with outcome inconsistencies (ß = -0.14; 95% CI, -0.22 - -0.01; P = 0.035). CONCLUSIONS: More than 1 in 10 trials reported outcomes inconsistent with those specified in trial registration websites, SAPs and protocols. An action plan is warranted to minimize selective reporting and improve transparency.

Physio-biochemical, agronomical, and gene expression analysis reveals different responsive approach to low nitrogen in contrasting rice cultivars for nitrogen use efficiency.

BACKGROUND: Nitrogen (N) is an essential macronutrient for plant growth and development as it is an essential constituent of biomolecules. Its availability directly impacts crop yield. Increased N application in crop fields has caused environmental and health problems, and decreasing nitrogen inputs are in demand to maintain crop production sustainability. Understanding the molecular mechanism of N utilization could play a crucial role in improving the nitrogen use efficiency (NUE) of crop plants. METHODS AND RESULTS: In the present study, the effect of low N supply on plant growth, physio-biochemical, chlorophyll fluorescence attributes, yield components, and gene expression analysis were measured at six developmental stages in rice cultivars. Two rice cultivars were grown with a supply of optimium (120 kg ha-1) and low N (60 kg ha-1). Cultivar Vikramarya excelled Aditya at low N supply, and exhibits enhanced plant growth, physiological efficiency, agronomic efficiency, and improved NUE due to higher N uptake and utilization at low N treatment. Moreover, plant biomass, leaf area, and photosynthetic rate were significantly higher in cv. Vikramarya than cv. Aditya at different growth stages, under low N treatment. In addition, enzymatic activities in cultivar Vikramarya were higher than cultivar Aditya under low nitrogen, indicating its greater potential for N metabolism. Gene expression analysis was carried out for the most important nitrogen assimilatory enzymes, such as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamate synthase (GOGAT). Expression levels of these genes at different growth stages were significantly higher in cv. Vikramarya compared to cv. Aditya at low N supply. Our findings suggest that improving NUE needs specific revision in N metabolism and physiological assimilation. CONCLUSION: Overall differences in plant growth, physiological efficiency, biochemical activities, and expression levels of N metabolism genes in N-efficient and N-inefficient rice cultivars need a specific adaptation to N metabolism. Regulatory genes may separately or in conjunction, enhance the NUE. These results provide a platform for selecting crop cultivars for nitrogen utilization efficiency at low N treatment.

Trends in Heart Failure-Related Mortality Among Older Adults in the United States From 1999-2019.

BACKGROUND: The U.S. population is aging with concurrent increases in heart failure (HF) burden. However, HF-related mortality trends among adults ≥75 years have not been investigated. OBJECTIVES: The purpose of this study was to assess the trends and regional differences in HF-related mortality among older adults in the United States. METHODS: Death certificates from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were examined from 1999 to 2019 for HF-related mortality in adults ≥75 years of age. Age-adjusted mortality rates (AAMRs) per 10,000 persons and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, and geographic region. RESULTS: Between 1999 and 2019, 5,014,919 HF-related deaths occurred among adults ≥75 years. The AAMR declined from 141.0 in 1999 to 108.3 in 2012 (APC: -2.1; 95% CI: -2.4 to -1.9), after which it increased to 121.3 in 2019 (APC: 1.7; 95% CI: 1.2-2.2). Men had consistently higher AAMR than women from 1999 (AAMR men: 158.3 vs women: 131.0) to 2019 (AAMR men: 141.1 vs women: 107.8). Non-Hispanic (NH) White adults had the highest overall AAMR (127.2), followed by NH Black (108.7), NH American Indian/Alaska Native (102.0), Hispanic or Latino (78.0), and NH Asian or Pacific Islander adults (57.1) AAMR also varied substantially by region (overall AAMR: Midwest 133.9; South: 119.2; West: 116.3; Northeast: 113.5), and nonmetropolitan areas had higher HF-related AAMR (147.0) than metropolitan areas (115.2). States in the top 90th percentile of HF-related AAMR were Mississippi, Oklahoma, West Virginia, Oregon, and Indiana, which had approximately double the AAMRs compared with states that fell into the lower 10th percentile. CONCLUSIONS: Following a period of steady decline, HF-related mortality in U.S. adults ≥75 years has increased since 2012. The highest AAMRs were observed among White adults and men, and among patients living in the Midwestern and nonmetropolitan United States. Targeted strategies are needed to prevent and treat HF among older adults to curb increasing levels of HF-related mortality.