Does off-hours endoscopic hemostasis affect outcomes of nonvariceal upper gastrointestinal bleeding?

Aim: Different researches showed controversial results about the ‘off-hours effect’ in nonvariceal upper gastrointestinal bleeding (NVUGIB). Materials & methods: A total of 301 patients with NVUGIB were divided into regular-hours group and off-hours group based on when they received endoscopic hemostasis, and the relationship of the clinical outcomes with off-hours endoscopic hemostasis was evaluated. Results: Patients who received off-hours endoscopy were sicker and more likely to experience worse clinical outcomes. Off-hours endoscopic hemostasis was a significant predictor of the composite outcome in higher-risk patients (adjusted OR: 4.63; 95% CI: 1.35–15.90). However, it did not associate with the outcomes in lower-risk patients. Conclusion: Off-hours effect may affect outcomes of higher-risk NVUGIB patients receiving endoscopic hemostasis (GBS ≥12).

Clinical Utility of KidneyIntelX in Early Stages of Diabetic Kidney Disease in the CANVAS Trial

<b><i>Introduction:</i></b> KidneyIntelX is a composite risk score, incorporating biomarkers and clinical variables for predicting progression of diabetic kidney disease (DKD). The utility of this score in the context of sodium glucose co-transporter 2 inhibitors and how changes in the risk score associate with future kidney outcomes are unknown. <b><i>Methods:</i></b> We measured soluble tumor necrosis factor receptor (TNFR)-1, soluble TNFR-2, and kidney injury molecule 1 on banked samples from CANagliflozin cardioVascular Assessment Study (CANVAS) trial participants with baseline DKD (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m² or urine albumin-to-creatinine ratio [UACR] ≥30 mg/g) and generated KidneyIntelX risk scores at baseline and years 1, 3, and 6. We assessed the association of baseline and changes in KidneyIntelX with subsequent DKD progression (composite outcome of an eGFR decline of ≥5 mL/min/year [using the 6-week eGFR as the baseline in the canagliflozin group], ≥40% sustained decline in the eGFR, or kidney failure). <b><i>Results:</i></b> We included 1,325 CANVAS participants with concurrent DKD and available baseline plasma samples (mean eGFR 65 mL/min/1.73 m² and median UACR 56 mg/g). During a mean follow-up of 5.6 years, 131 participants (9.9%) experienced the composite kidney outcome. Using risk cutoffs from prior validation studies, KidneyIntelX stratified patients to low- (42%), intermediate- (44%), and high-risk (15%) strata with cumulative incidence for the outcome of 3%, 11%, and 26% (risk ratio 8.4; 95% confidence interval [CI]: 5.0, 14.2) for the high-risk versus low-risk groups. The differences in eGFR slopes for canagliflozin versus placebo were 0.66, 1.52, and 2.16 mL/min/1.73 m² in low, intermediate, and high KidneyIntelX risk strata, respectively. KidneyIntelX risk scores declined by 5.4% (95% CI: −6.9, −3.9) in the canagliflozin arm at year 1 versus an increase of 6.3% (95% CI: 3.8, 8.7) in the placebo arm (<i>p</i> &#x3c; 0.001). Changes in the KidneyIntelX score at year 1 were associated with future risk of the composite outcome (odds ratio per 10 unit decrease 0.80; 95% CI: 0.77, 0.83; <i>p</i> &#x3c; 0.001) after accounting for the treatment arm, without evidence of effect modification by the baseline KidneyIntelX risk stratum or by the treatment arm. <b><i>Conclusions:</i></b> KidneyIntelX successfully risk-stratified a large multinational external cohort for progression of DKD, and greater numerical differences in the eGFR slope for canagliflozin versus placebo were observed in those with higher baseline KidneyIntelX scores. Canagliflozin treatment reduced KidneyIntelX risk scores over time and changes in the KidneyIntelX score from baseline to 1 year associated with future risk of DKD progression, independent of the baseline risk score and treatment arm.

Effect of a low-salt diet on chronic kidney disease outcomes: a systematic review and meta-analysis

ObjectiveThe benefits of a low-salt diet for patients with chronic kidney disease (CKD) are controversial. We conducted a systematic review and meta-analysis of the effect of a low-salt diet on major clinical outcomes.DesignSystematic review and meta-analysis.Data sourcesMEDLINE by Ovid, EMBASE and the Cochrane Library databases.Eligibility criteria for selecting studiesWe included randomised controlled trials (RCTs) and cohort studies that assessed the effect of a low-salt diet on the renal composite outcomes (more than 50% decline in estimated glomerular filtration rate (eGFR) during follow-up, doubling of serum creatinine or end-stage renal disease), rate of eGFR decline, change in proteinuria, all-cause mortality events, cardiovascular (CV) events, and changes in systolic blood pressure and diastolic blood pressure.Data extraction and synthesisTwo independent researchers extracted data and evaluated their quality. Relative risks (RRs) with 95% CIs were used for dichotomous data. Differences in means (MDs) or standardised mean differences (SMDs) with 95% CIs were used to pool continuous data. We used the Cochrane Collaboration risk-of-bias tool to evaluate the quality of RCTs, and Newcastle–Ottawa Scale to evaluate the quality of cohort studies.ResultsWe found 9948 potential research records. After removing duplicates, we reviewed the titles and abstracts, and screened the full text of 230 publications. Thirty-three studies with 101 077 participants were included. A low-salt diet produced a 28% reduction in renal composite outcome events (RR: 0.72; 95% CI: 0.58 to 0.89). No significant effects were found in terms of changes in proteinuria (SMD: −0.71; 95% CI: −1.66 to 0.24), rate of eGFR (decline MD: 1.16; 95% CI: −2.02 to 4.33), risk of all-cause mortality (RR: 0.92; 95% CI: 0.58 to 1.46) and CV events (RR: 1.01; 95% CI: 0.46 to 2.22).ConclusionA low-salt diet seems to reduce the risk for renal composite outcome events in patients with CKD. However, no compelling evidence indicated that such a diet would reduce the eGFR decline rate, proteinuria, incidence of all-cause mortality and CV events. Further, more definitive studies are needed.PROSPERO registration numberCRD42017072395.

Risk of Cardiovascular Events after Covid-19: a double-cohort study

Objective: To determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular events and all-cause mortality. Methods: We conducted a retrospective double-cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection [COVID-19(+) cohort] and its documented absence [COVID-19(-) cohort]. The study investigators drew a simple random sample of records from all Oregon Health & Science University (OHSU) Healthcare patients (N=65,585) with available COVID-19 test results, performed 03.01.2020 - 09.13.2020. Exclusion criteria were age < 18y and no established OHSU care. The primary outcome was a composite of cardiovascular morbidity and mortality. All-cause mortality was the secondary outcome. Results: The study population included 1355 patients (mean age 48.7 ± 20.5 y; 770(57%) female, 977(72%) white non-Hispanic; 1072(79%) insured; 563(42%) with cardiovascular disease (CVD) history). During a median 6 months at risk, the primary composite outcome was observed in 38/319 (12%) COVID-19(+) and 65/1036 (6%) COVID-19(-) patients (p=0.001). In Cox regression adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk of the primary composite outcome (HR 1.71; 95%CI 1.06-2.78; p=0.029). Inverse-probability-weighted estimation, conditioned for 31 covariates, showed that for every COVID-19(+) patient, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19(-): average treatment effect on the treated -65.5 (95%CI -125.4 to -5.61) days; p=0.032. Conclusions: Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.

Real-World Comparative Cost-Effectiveness Analysis of Different Classes of Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in Saudi Arabia

The very fact that multiple sclerosis (MS) is incurable and necessitates life-long care makes it one of the most burdensome illnesses. The aim of this study was to compare the cost-effectiveness of orally administered medications (e.g., fingolimod, dimethyl fumarate, and teriflunomide), interferon (IFN)-based therapy, and monoclonal antibodies (MABs) (e.g., natalizumab and rituximab) in the management of relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia using real-world data. This was a retrospective cohort study in which patients with RRMS aged ≥18 years without any other chronic health conditions with non-missing data for at least 12 months were recruited from the electronic health records of a university-affiliated tertiary care center. Multiple logistic regressions controlling for age, sex, and duration of therapy were conducted to examine the odds of disability progression, clinical relapse, MRI lesions, and composite outcome (e.g., relapse, lesion development on MRI, disability progression). The number of patients who met the inclusion criteria and were included in the analysis was 146. Most of the patients were female (70.51%) and young (e.g., ≤35 years of age). There were 40 patients on the orally administered agents (e.g., dimethyl fumarate, teriflunomide, fingolimod), 66 patients were on IFN-based therapy (e.g., Rebif®), and 40 patients were on monoclonal antibodies (e.g., rituximab and natalizumab). Patients on MABs had lower odds of the composite outcome (OR = 0.17 (95% CI: 0.068–0.428)). The use of orally administered agents was dominant (e.g., more effective and less costly), with average annual cost savings of USD −4336.65 (95% CI: −5207.89–−3903.32) and 8.11% higher rate of effectiveness (95% CI: −14.81–18.07) when compared with Rebif®. With regard to the use of MABs in comparison to Rebif®, MABs were associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 1381.54 (95% CI: 421.31–3621.06) and 43.11% higher rate of effectiveness (95% CI: 30.38–61.15) when compared with Rebif®. In addition, the use of MABs was associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 5717.88 (95% CI: 4970.75–8272.66) and 35% higher rate of effectiveness (95% CI: 10.0–42.50) when compared with orally administered agents. The use of MABs in the management of RRMS among the young patient population has shown to be the most effective therapy in comparison to both IFN-based therapy (e.g., Rebif®) and orally administered agents, but with higher cost. Orally administered agents resulted in better outcomes and lower costs in comparison to IFN-based therapy. Future studies should further examine the cost-effectiveness of different disease-modifying therapies for the management of RRMS using more robust study designs.

Retrospective comparison of open vs minimally invasive cystotomy in 28 cats using a composite outcome score

Objectives The aim of this study was to compare the outcomes of cats undergoing open cystotomy with those undergoing minimally invasive surgery (MIS) for removal of cystic calculi by use of a composite outcome score. Methods Twenty-eight cats were retrospectively enrolled and divided into two groups: open cystotomy (n = 14) and MIS (n = 14). The primary outcome measure was a composite outcome score, including three variables: pain scores ⩾2 at either 6 or 12 h postoperatively; failure to remove all stones as determined by postoperative radiographs; and postoperative complications requiring a visit to the hospital separate from the planned suture removal appointment. Other data collected included signalment, history, other procedures performed during anesthesia, willingness to eat the day after surgery and the financial cost of the procedures. Results There was no significant difference in age, weight, sex or breed between the two groups. The risk of experiencing the composite outcome was 3/14 (21.4%) in the MIS group and 10/14 (71%) in the open procedure group ( P = 0.02). The cats in the open surgery group had 8.3 times greater odds of developing the composite outcome than cats in the MIS group (odds ratio 8.3, 95% confidence interval 1.3–74.4; P = 0.02). In the MIS group, 10/14 cats were eating the day after surgery vs 3/14 in the open procedure group ( P = 0.02). The procedural cost was higher in the MIS group, with a median cost of US$945 (interquartile range [IQR] US$872–1021) vs US$623 (IQR US$595–679) in the open group ( P <0.01). Conclusions and relevance In this study the composite outcome score provided evidence to support the use of MIS techniques in cats with cystic calculi. The composite outcome score should be considered in future veterinary studies as a promising method of assessing clinically relevant outcomes.

Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial

Folic acid (FA) supplementation prevents neural tube defects (NTDs), but the effects on other reproductive outcomes are unclear. While common recommendation is 0.4 mg/day in addition to regular nutrition, the most appropriate dose of FA is still under debate. We investigated the effects of a higher dose of periconception FA on reducing adverse reproductive outcomes. In this multicenter double-blind randomized controlled trial (RCT), 1060 women (aged 18–44 years and planning a pregnancy) were randomly assigned to receive 4.0 mg or 0.4 mg of FA daily. The primary outcome was the occurrence of congenital malformations (CMs). A composite outcome including one or more adverse pregnancy outcomes was also evaluated. A total of 431 women had a natural conception within 1 year. The primary outcome occurred in 8/227 (3.5%) women receiving 4.0 mg FA and 9/204 (4.4%) women receiving 0.4 mg FA (RR 0.80; 95%CI 0.31 to 2.03). The composite outcome occurred in 43/227 (18.9%) women receiving 4.0 mg FA and 75/204 (36.8%) women receiving 0.4 mg FA (RR 0.51; 95%CI 0.40 to 0.68). FA 4.0 mg supplementation was not associated with different occurrence of CMs, compared to FA 0.4 mg supplementation. However, FA 4.0 mg supplementation was associated with lower occurrence of other adverse pregnancy outcomes.

490 Right ventricular free wall longitudinal strain negatively impacts prognosis of patients with functional mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair

Aims Although right ventricular (RV) systolic dysfunction seems to be associated with adverse outcome after transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip system, the prognostic value of RV free wall longitudinal strain (RVFWLS) in this setting has not been yet investigated. The aim of this study is to evaluate RVFWLS as predictor of outcome in patients with severe or moderate-to-severe functional MR undergoing TEER and its prognostic role compared with tricuspid annular plane systolic excursion (TAPSE). Methods and results 102 patients [73 (IQR: 66.8–77.0) years, 73 males (71.6%)] were retrospectively selected from March 2012 to February 2021. Echocardiograms were performed by using General Electric machines. RVFWLS was assessed through RV modified apical 4-chamber view, setting the region of interest to minimum size. Values of RVFWLS &gt; −20% were recognized as abnormal. We considered a composite endpoint including rehospitalization for heart failure (HF) and overall death as primary outcome. Secondary outcomes were overall death, cardiac death and rehospitalization for HF. All patients were assessed at the longest available follow-up [median 22.1 (IQR: 9.7–49.3) months]. Baseline clinical and echocardiographic characteristics are listed in Table 1. Primary outcome was found in 60 (58.8%) patients, while secondary outcomes, i.e. overall death, cardiac death and rehospitalization for HF, were found respectively in 50 (50.0%), 31 (30.4%), and 36 (35.3%) patients. Mean TAPSE was 16.7 ± 4.0 mm and mean RVFWLS was −16.9 ± 6.0%. At univariable analysis both TAPSE (HR: 0.907, CI: 0.848–0.970, P-value: 0.004) and RVFWLS (HR: 0.937, CI: 0.897–0.979, P-value: 0.004) were significantly associated with the primary outcome. Kaplan–Meier survival curves showed that patients with TAPSE &lt;17 mm had a lower survival free from the composite outcome compared with those with TAPSE ≥17 mm (Log-Rank = 0.030); patients with RVFWLS value &gt; −20% also showed a lower survival free from the composite outcome compared with patients with RVFWLS ≤ −20% (Log Rank 0.004). Among patients with preserved RV systolic longitudinal function as indicated by TAPSE ≥ 17 mm, subjects with RVFWLS &gt; −20% had a significantly higher incidence of the composite outcome compare with those with RVFWLS ≤ −20% (Log-Rank = 0.008). Conversely, no difference was found among patients with TAPSE &lt;17 mm. Conclusions RV dysfunction assessed either by TAPSE and RVFWLS is associated with poorer outcome in patients with severe or moderate-to-severe functional MR undergoing TEER. Compared with TAPSE, RVFWLS seems to be superior in identifying patients at higher risk of adverse events during follow-up. Our data encourage the use of this speckle tracking-derived echocardiographic parameter in routinely evaluation of patients with functional MR candidate for TEER.