Primary Composite Outcome Research Articles

Effect of a perineal protection device in vacuum-assisted births—a prospective randomized controlled interventional trial

BackgroundBirth tears are common after vaginal birth with a prevalence of up to 85%, especially in vaginal-assisted births. As birth trauma can cause physical and psychological short-term and long-term maternal morbidity, it is essential to improve maternal outcome at birth. ObjectiveTo evaluate the effect of a perineal protection device on the rate of spontaneous birth tears in the posterior compartment in vacuum-assisted births, as well as the feasibility and safety of the device. Study DesignIn a prospective, randomized controlled interventional trial from July 2020 to October 2022 we evaluated the application of a perineal protection device in vacuum-assisted vaginal births in a tertiary care center. 1998 patients were asked for participation, and 1574 patients with singletons ≥ 36 weeks of gestation gave their informed consent before birth. Ultimately, 209 were included according to a power calculation performed in advance with a statistical power of 80% and a significance level of 5% in expectation to reduce the rate for the primary composite outcome by 20%. The primary composite outcome was the rate of low-grade perineal and/or vaginal tears in the posterior compartment. Secondary outcomes were the rate of high-grade perineal tears and episiotomies, the feasibility of the device, and its safety for mother and child. Descriptive statistics and a logistic regression analysis were performed in an “intention-to-treat” (ITT), a “per-protocol” (PP), and an “as-treated” (AT) analysis, using SPSS version 29.0.0.0 (IBM SPSS, Armonk, New York, USA) and the software “R” (The R Project for Statistical Computing, version 3.5.0). A p-value < 0.05 was considered statistically significant. ResultsOf the 1574 patients, 249 (15.8%) had an indication for vacuum-assisted vaginal birth, of which 217 (13.8%) were randomized. Another eight patients (0.5%) were excluded because of birth ending without vacuum-assistance. Of the remaining 209 patients, 105 formed the intervention group (application of the device), whereas 104 formed the control group (without application of the device). No differences in primary and secondary outcomes were found in the ITT and PP analysis. In the ITT analysis, 79 patients (75.2%) in the intervention group compared to 73 patients (70.2%) in the control group (p = 0.4) met the primary endpoint. In the PP analysis, the primary composite outcome was seen 53 patients (77.9%) in the intervention group compared to 73 patients (70.2%) in the control group (p = 0.27). For the AT analysis, 68 of the 105 patients (65%) remained in the intervention group after exclusion of 37 (35%) patients with failed application of the device. Consequently, 141 formed the control group. In the AT analysis, there was also no difference in the primary composite outcome between the two groups (53 patients (77.9%) in the intervention group compared to 99 patients (70.2%) in the control group). However, within the secondary outcomes, we found a significantly lower rate of mediolateral episiotomies in the intervention group (29% vs 45%, p = 0.034). No adverse outcomes for mother and child were seen. In one third of cases, the device was difficult to place correctly and/or to keep correctly in place. ConclusionThe perineal protection device was not able to reduce the primary composite outcome of the study in women giving birth by vacuum-assistance. Although this was not the primary end point, a lower rate of mediolateral episiotomies was observed, if the device had been used correctly. As a limitation, difficulties with the application of the device occurred in 33% of cases. Nevertheless, no adverse events in association with the device were observed for either mother or child in our cohort. Video Abstract [Display omitted]

GLP1R Gene Expression and Kidney Disease Progression

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control. To investigate the association of genetically proxied GLP-1RAs with kidney disease progression. This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024. Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project. The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression. Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status. In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.

Bilateral ultrasound-guided erector spinae plane block for postoperative analgesia in paediatric idiopathic scoliosis patients undergoing posterior spine fusion surgery: a randomized controlled trial.

Major spinal surgery causes severe pain. We examined the ability of erector spinae plane block (ESPB) to alleviate pain after posterior spinal fusion (PSF) in paediatric scoliosis patients. Seventy-two patients who underwent PSF were randomized into a preoperative ultrasound-guided ESPB group or a no-block control group. The composite primary outcome was the area under the curve (AUC) of the numerical rating scale (NRS) score in the first 24h after surgery and the number of parent-controlled intravenous analgesia (PCIA) boluses administered 24h after surgery. The secondary outcomes included the NRS score, opioid consumption, rescue analgesia, adverse events, and quality of recovery. The AUC-NRS at rest was 62 (13) in the ESPB group and 89 (13) in the control group (P < 0.001). There were 15 (5) 24-h PCIA boluses administered in the ESPB group and 30 (7) in the control group (P < 0.001). Compared with those in the control group, the NRS scores at rest were lower in the ESPB group at 0, 3, 6, and 9h postoperatively, and the NRS scores during movement were lower in the ESPB group at 0, 3, 6, 9 and 12h postoperatively. The ESPB group showed a lower need for PCIA than did the control group at 0-6, 6-12, 12-18 and 1-24h postoperatively. In the ESPB group, fewer patients required rescue analgesics, and patients exhibited a higher quality of recovery. Preoperative ESPB improves postoperative analgesia in paediatric scoliosis patients who underwent PSF. ChiCTR2300074505. August 8, 2023.

A comparison of the safety and effectiveness of insulin aspart with other bolus insulins in women with pre-existing Type 1 diabetes during pregnancy: A post hoc analysis of a prospective cohort study.

The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

Noninvasive risk assessment and prediction of cardiac outcomes in patients with congestive heart failure or myocardial infarction

BackgroundHeart rate turbulence (HRT) and T-wave alternans (TWA), recognized as promising noninvasive markers for ventricular tachyarrhythmias and cardiac death, have been studied predominantly in Western populations, specifically in patients with myocardial infarction (MI) or heart failure (HF) with reduced ejection fraction (EF). ObjectiveThe purpose of this study was to investigate the clinical implications of HRT and TWA in predicting adverse cardiac events, including cardiac death, ventricular tachyarrhythmia, and heart failure–related hospitalization (HFH). MethodsThe K-REDEFINE study, a prospective, observational, multicenter analysis of 26 tertiary hospitals in South Korea, investigated the prognostic implications of Holter-based variables including HRT and TWA in 1116 patients with acute MI or HF (age 60.8 ± 2.9 years; 76.3% male). All participants underwent 24-hour Holter recording within 6.8 ± 16.5 days after hospitalization. The primary composite outcome included cardiac death, ventricular tachyarrhythmias, and HFH. ResultsDuring 4.3 ± 1.2 years of follow-up, impaired HRT demonstrated the most powerful predictive value for the composite (adjusted hazard ratio [aHR] 3.41, 95% confidence interval [CI] 2.27–5.13) or individual events: cardiac death (aHR 4.08, 95% CI 2.17–7.70), ventricular tachyarrhythmia (aHR 3.72, 95% CI 1.29–10.77), and HFH (aHR 4.32, 95% CI 2.25–8.28). The predictive power of abnormal HRT remained consistently significant across subgroups of MI and HF, or across varying degrees of EF. When combined with reduced EF (<50%), the predictive power was further enhanced. However, abnormal TWA was significantly associated only with the composite outcome (aHR 1.51, 95% CI 1.06–2.16). ConclusionThe K-REDEFINE study identified abnormal HRT, mostly assessed within 1 month after hospitalization, as a significant predictor not only for cardiac death and ventricular tachyarrhythmia but also for HFH.

Patients with Inflammatory Bowel Disease are at Increased Risk for Complications of Herpes Zoster

Background and aimsPatients with inflammatory bowel disease (IBD) are at an increased risk for vaccine-preventable diseases, such as herpes zoster (HZ). The aim of this study was to determine whether complications of HZ are more frequent in patients with IBD than in non-IBD controls. MethodsThis was a retrospective, cohort study using the Optum Research Database. Patients with IBD were matched 1:1 to non-IBD controls based on age, sex, and index year, which was defined as the diagnosis of HZ. We then identified the complications of HZ that occurred up to 90 days after the index date. We compared patients with IBD with non-IBD controls and evaluated the 90-day risk of HZ complications. We used a composite primary outcome for any HZ complication. Secondary outcomes were risk factors for complications. ResultsFour thousand seven fifty-six patients with IBD met the inclusion criteria and were matched to the controls. Patients with IBD were more likely to have complications of HZ than controls [738 (15.52%) vs. 595 (12.51%), p < 0.0001]. Patients with IBD with higher comorbidity scores were more likely to develop complications (1.86 vs. 1.18 p < 0.0001). In the logistic regression analysis of patients with IBD having a higher comorbidity score, above 50 years of age, on anti-TNF or corticosteroids were all at increased risk of a complication of HZ. ConclusionPatients with IBD are more likely to have complications of HZ than controls. Efforts are needed to increase HZ vaccine uptake to reduce the morbidity of HZ.

Composite Primary Outcome Variables in Nephrology Clinical Trials

Composite Primary Outcome Variables in Nephrology Clinical Trials

Effect of a campaign with oral polio vaccine on general health: A cluster-randomised trial in rural Guinea-Bissau

To investigate in a cluster-randomised trial whether a campaign with oral polio vaccine (C-OPV) reduced mortality and morbidity. We randomised 222 village clusters under demographic surveillance to an intervention (health check and C-OPV) or control group (health check only). Children aged 0-8 months were eligible. In Cox proportional hazards models with age as the underlying timescale, we compared rates of non-accidental mortality/hospital admission (composite primary outcome) during 12 months of follow-up. Secondary analyses considered non-accidental admission and mortality as separate outcomes. Potential effect modifiers identified in prior studies including sex, season, and timing of the first routine OPV dose (OPV0, scheduled at birth) were assessed. Among 10,175 children (5,288 in 111 intervention clusters/4,887 in 111 control clusters), we observed 265 deaths/admissions during 7,616 person-years at risk (intervention: 129; control: 136). C-OPV did not reduce the composite endpoint, hazard ratio (HR): 0.87, 95%CI: 0.68-1.12 or its separate components. C-OPV reduced the risk in children receiving OPV0<15 days of birth (HR=0.66, 95%CI: 0.46-0.95), but not in other children (p for interaction: 0.03). Interactions for other potential effect modifiers were not statistically significant. C-OPV had no overall effect on mortality/admissions, but the effect differed by early priming with OPV0.

Finerenone Improves Outcomes in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction Irrespective of Age: A Prespecified Analysis of FINEARTS-HF.

Background: Finerenone improves outcomes in patients with HF and mildly reduced or preserved ejection fraction (HFmrHF/HFpEF). It is important to understand the efficacy and safety of finerenone in these patients according to age. Methods: The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone trial to investigate efficacy and safety compared to placebo in patients with heart failure). A total of 6,001 patients aged 40-97 years were stratified by quartile (Q 1-4) of baseline age: Q1 40-66 years (n=1,581), Q2 67-73 years (n=1,587), Q 3 74-79 years (n=1,421), and Q4 ≧ 80 years (n=1,412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) HF events, including HF hospitalization or urgent HF event, along with secondary efficacy and safety outcomes. Results: The incidence of primary outcome increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: RR (95% CI) Q1 0.70 (0.53- 0.92), Q2 0.83 (0.64-1.07), Q3 0.98 (0.76-1.26), and Q4 0.85 (0.67-1.07); p for interaction =0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change (95% CI) Q1 2.87 (1.09-4.66), Q2 1.24 (-0.59-3.07), Q3 0.94 (-0.98-2.86), and Q4 1.24 (-0.90-3.38); P-interaction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age. Conclusions: In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome, and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age. Trial Registration: URL: https://clinicaltrials.gov Unique Identifiers: NCT04435626 and EudraCT 2020-000306-29.

Effectiveness of comprehensive geriatric assessment adapted to primary care when provided by a nurse or a general practitioner: the CEpiA cluster-randomised trial

BackgroundThe benefits of comprehensive geriatric assessment (CGA) are well established for hospital care but less so for primary care. Our primary objective was to assess the effect of two multifaceted interventions based on a CGA adapted for primary care on a composite criterion combining all-cause mortality, emergency department visits, unplanned hospital admissions, and institutionalisation.MethodsThis open-label, pragmatic, three-arm, cluster-randomised controlled trial involved 39 general practices in France. It included 634 patients aged 70 years or over with chronic health conditions and/or an unplanned hospital admission in the past 3 months, between 05/2016 and 08/2018. Interventions were in arm 1: a systematic nurse-led CGA; arm 2: a GP-led CGA, at the GP’s discretion; arm 3: standard care. The primary composite endpoint was assessed at 12 months. The secondary endpoints included: components of the composite endpoint, health-related quality of life (Duke Health Profile), functional status (Katz Activities of Daily Living Index) and medications (number) at 12 months. Pairwise comparisons between the experimental groups and the control were tested. The main analysis was performed on the intention-to-treat (ITT) population, after imputing missing information and adjusting for baseline imbalances by mixed effects regressions.ResultsFor the primary composite outcome, no statistically significant difference was found between arm 1 and the control (adjusted odds ratio [aOR] = 0.81 [95%CI 0.54–1.21], P = 0.31), whereas arm 2 and the control differed significantly (aOR = 0.60 [0.39–0.93], P = 0.022). A statistically lower risk of unplanned hospital admission in arm 2 vs control (aOR = 0.57 [0.36–0.92], P = 0.020)) was observed, while no statistically significant differences were found for the other components and between arm 1 and the control. None of the other secondary endpoints differed between arms.ConclusionsOur study led in community-dwelling older patients with chronic conditions found no significant effect of a CGA adapted for primary care on mortality, functional independence and quality of life, but suggests that a GP-led CGA may reduce the risk of unplanned hospital admission. Our study demonstrates the feasibility of incorporating CGA into clinical practice and highlights its potential benefits when applied on a case-by-case basis, guided by the GPs who develop the resulting PCP.Trial registrationNCT02664454.

The safety of same-day discharge following percutaneous coronary intervention in regional Australia.

Same-day discharge (SDD) following percutaneous coronary intervention (PCI) has proven safe, and global adoption of this strategy has been increasing rapidly. These data are predominantly derived from high-volume, metropolitan centres with a relative paucity of data from regional and remote settings. The primary objective of this study was to evaluate the outcomes of a same-day, criteria-led discharge strategy following elective transradial PCI in a regional setting. This is a retrospective, single-centre cohort study. Consecutive outpatients aged ≥18 years presenting for elective transradial invasive coronary angiography between March 2019 and February 2024 were included in the analysis. We report the primary composite outcome of 30-day all-cause mortality and unplanned hospital readmission and compare proportions between those who were discharged on the day of their procedure with those admitted overnight in hospital and discharged the next day. A total of 555 eligible patients were identified, of which 330 (60%) were discharged on the day of their procedure. The composite primary end-point occurred in seven (2%) of the SDD patients and in six (3%) of the overnight admission patients (relative risk = 0.80; 95% confidence interval = 0.27-2.34; P = 0.68). No significant differences were seen in rates of readmission, or in other clinical outcomes assessed, including death, myocardial infarction, stroke and vascular complications or bleeding. In a regional setting, SDD following elective transradial PCI, in select patients, is a safe approach which was not associated with higher rates of unplanned readmission or adverse clinical outcomes.

Ferritin, inflammation, and iron deficiency in acute heart failure: evidence from the EDIFICA cohort

Abstract Background Ferritin is commonly used to evaluate iron stores and guide therapeutic decisions regarding intravenous iron supplementation. However, in the context of AHF, inflammation-driven upregulation of ferritin might disrupt its correlation with iron stores, restricting iron bioavailability and potentially amplifying the inflammatory response. Aim This study aims to assess the clinical and prognostic associations of ferritin levels in an AHF cohort and to determine whether the prognostic value of ferritin is influenced by the presence of infection, inflammatory activation, and other markers of iron deficiency. Methods The association between ferritin and clinical outcomes (180 days) in AHF was evaluated in a cohort of 526 patients from the EDIFICA registry. Results The median ferritin plasma concentration at admission was 180 pg/mL. Patients with higher ferritin levels at admission were predominantly men, exhibiting a high prevalence of chronic kidney disease and alcohol consumption, and presenting with lower blood pressure and a higher incidence of clinical infection. Higher ferritin levels were associated with increased risk of the composite of heart failure hospitalization or cardiovascular death (Tertile 2: HR 1.75; 95% CI 1.10–2.79; p = 0.017; Tertile 3: HR 1.79; 95% CI 1.08–2.97; p = 0.025), independently of classical HF prognostic factors, inflammatory and iron-related markers. No significant associations were found between admission serum iron or transferrin saturation tertiles, iron status categories, or guideline-defined iron deficiency (ID) criteria and the primary composite outcome. However, at discharge, patients who met the criteria for defective iron utilization, low iron storage, or guideline-defined ID had a lower risk of the composite endpoint compared to those with normal iron utilization or who did not meet the guideline-defined ID criteria, respectively. Conclusions Elevated ferritin levels are independently associated with poor prognosis in AHF. Low ferritin levels are associated with a favorable outcome and do not carry significant value in identifying ID in this population.

Implications of Myocardial Strain in Primary Mitral Regurgitation - A Cardiovascular Magnetic Resonance Study.

Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodeling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction. Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine-images. The aim of this study was to evaluate the prognostic value of CMR feature-tracking derived GLS in patients with primary MR. Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patient with LV ejection fraction <50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised of 1) referral for mitral surgery due to symptoms or LV systolic dysfunction or 2) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). On multivariable analysis, GLS≥ -16.6% was associated with primary outcome (hazard ratio 1.90,p=0.01). In moderate MR cohort, patient with GLS≥ -16.6% had worse event-free survival while no significant different in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (hazard ratio 2.24,p=0.02). In primary MR patients with preserved systolic function, GLS was associated with our composite outcomes and all-cause death. GLS may serve as a marker of cardiac dysfunction in primary MR patients with preserved systolic function allowing identification of patients likely to decompensate during observation.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Open versus robotic retromuscular ventral hernia repair: outcomes of the ORREO prospective randomized controlled trial.

Robotic retromuscular ventral hernia repair (rRMVHR) potentially combines the best features of open and minimally invasive VHR: myofascial release with abdominal wall reconstruction (AWR) with the lower wound morbidity of laparoscopic VHR. Proliferation of this technique has outpaced the data supporting this claim. We report 2-year outcomes of the first randomized controlled trial of oRMVHR vs rRMVHR. Single-center randomized control trial of open vs rRMVHR. 100 patients were randomized (50 open, 50 robotic). We included patients > 18 y/o with hernias 7-15cm with at least one of the following: diabetes, chronic obstructive pulmonary disease (COPD), body mass index (BMI) ≥ 30, or current smokers. Primary outcome was occurrence of a composite outcome of surgical site infection (SSI), non-seroma surgical site occurrence (SSO), readmission, or hernia recurrence. Secondary outcomes were length of stay, any SSI or SSO, SSI/SSOPI, operative time, patient reported quality of life, and cost. Analysis was performed in an intention-to-treat fashion. Study was funded by a grant from Society of American Gastrointestinal and Endoscopic Surgeons. 90 patients were available for 30-day and 62 for 2-year analysis (rRMVHR = 46 and 32, oRMVHR = 44 and 30). Hernias in the open group were slightly larger (10 vs 8cm, p = 0.024) and more likely to have prior mesh (36.4 vs 15.2%; p = 0.030), but were similar in length, prior hernia repairs, mesh use, and myofascial release. There was no difference in primary composite outcome between oRMVHR and rRMVHR (20.5 vs 19.6%, p = 1.000). Median length of stay was shorter for rRMVHR (1 vs 2days; p < 0.001). All patients had significant improvement in quality of life at 1 and 2years. Other secondary outcomes were similar. There is no difference in a composite outcome including SSI, SSOPI, readmission, and hernia recurrence between open and robotic RMVHR.

A Prospective European Trial Comparing Laparotomy, Laparoscopy, Robotic-Assisted, and Transanal Total Mesorectal Excision Procedures in High-Risk Patients with Rectal Cancer: The RESET Trial.

To compare total mesorectal excision (TME) techniques combined with sphincter-sparing procedure in high-risk patients (HRPs). TME is the standard treatment for rectal cancer, but can be challenging in HRPs. The available surgical approaches must be compared, especially in HRPs. Prospective, observational, multicenter trial to compare laparotomy (OTME), laparoscopy (LTME), robotic-assisted surgery (RTME), and transanal surgery (TaTME) in HRPs. The composite primary outcome included circumferential radial margin (CRM) ≥1mm, TME grade II-III, and absence of Clavien-Dindo grade III-IV complications. Three propensity score analyses were performed (LTME vs. RTME, RTME vs. TaTME, LTME vs. TaTME). 1078 HRPs (75% of men, median body mass index of 27kg/m2, 50% of tumors in the lower third of the rectum) underwent surgery. The RTME and TaTME groups included patients with more advanced and lower tumors and coloanal anastomosis (P<0.001). Operative time was longer for RTME surgery (P<0.001). Conversion rate was similar for minimally invasive procedures (4.5%). The global R0 resection rate was 96% without difference among techniques. The primary outcome rates were 82.4%, 64.3%, 74.7%, and 80.3% for LTME, OTME, RTME, and TaTME, respectively. None achieved the expected success rate (85%), and propensity score analyses found no differences. Operative results were similar between high- and low-volume inclusion centers only for RTME. The RESET trial yielded high-quality results despite focusing on HRPs. Minimally invasive procedures showed similar sphincter-sparing procedure outcomes, but LTME included patients with more favorable tumors. Oncologic and functional outcomes will be evaluated at 2 years (ClinicalTrials.gov, ID: NCT03574493).

Insights on prevalence and incidence of anemia and rapid up-titration of oral heart failure treatment from the STRONG-HF study.

Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers. The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment. The design and main results of the study have been previously described. Patients were randomized within 2days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90days were investigated. The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin. Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition.

Controlling Nutritional Status Score Predicts 1-Year Outcomes in Chronic Thromboembolic Pulmonary Hypertension.

The prognosis for patients with chronic thromboembolic pulmonary hypertension (CTEPH) using their nutritional status has not been established. We investigated the relationship between the prognosis of patients with CTEPH and the Controlling Nutritional Status (CONUT) score, which is a nutritional assessment tool. A total of 157 patients with CTEPH was enrolled in the study. The primary outcome was defined as the composite outcome of all-cause mortality and non-elective hospitalization due to heart failure. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff CONUT score for predicting the 1-year rate of the primary outcome. Patients were divided into 2 groups according to the significant cutoff value and compared. Undernutrition was observed in 51.6% of patients. ROC analysis revealed a significant cutoff CONUT score of 3.5 (area under the curve=0.789). The incidence rate of the primary composite outcome was higher in the high CONUT group (score ≥4) than in the low CONUT group (score ≤3; 20% vs. 2.2%; P<0.001). Cox analysis revealed the CONUT score per point increase was an independent risk factor for the primary composite outcomes (hazard ratio 2.301; 95% confidence interval 1.081-4.895; P=0.031). The CONUT score can predict the 1-year rate of all-cause death and non-elective hospitalization in patients with CTEPH.

Contemporary Outcomes of Infrainguinal Vein Bypass Surgery for Chronic Limb-Threatening Ischaemia: A Two-Centre Cross-Sectional Study.

Background/Objectives: Chronic limb-threatening ischaemia (CLTI) is a significant life and limb-threatening condition. Two recent seminal trials, BEST-CLI and BASIL-2, have provided seemingly conflicting results concerning the optimal treatment modality for patients with CLTI. We sought to investigate the outcomes of patient undergoing infrainguinal bypass at two centres in Aotearoa New Zealand. Methods: A cross-sectional retrospective review of all patients who underwent infrainguinal bypass grafting for CLTI at Auckland City Hospital and Waikato Hospital between January 2020 and December 2021 was performed. The primary outcome was a composite of death, above-ankle amputation, and major limb reintervention. The secondary outcome was minor limb reintervention. Kaplan-Meier survival analysis was performed to determine time to the primary and secondary endpoints. Demographic factors were examined using the log-rank test to examine the effect on the outcome. Results: One hundred and nineteen patients who underwent infrainguinal bypass for CLTI in the study period were identified. Of these, 93 patients had a bypass with ipsilateral or contralateral GSV. The median follow-up time was 1.85 years. The most common indication for surgery was tissue loss (69%, n = 63), with the most common distal bypass target being the below-knee popliteal artery (45%, n = 41). The primary composite outcome occurred in 42.8% of the cohort (n = 39). Death was the most common component of the primary outcome (26%, n = 24). Male sex (HR 0.48, 95% CI 0.26-0.88, p = 0.018) and statin use (HR 0.49, 95% CI 0.24-0.98, p = 0.044) were independent predictors of protection from the composite outcome on multivariate analysis. Dialysis dependence (HR 3.32, 95% CI 1.23-8.99, p = 0.018) was an independent predictor for patients meeting the composite outcome. Conclusions: This study's results are consistent with the published outcomes of BEST-CLI. The patient cohorts examined, anatomical disease patterns, and conduit use may explain some of the differences observed between this study, BEST-CLI and BASIL-2. Further work is required to define the specific patient populations who will benefit most from an open surgical or endovascular first approach to the management of CLTI.

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: Rationale and design of the CRAFT trial

BackgroundCo-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. MethodsThe Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. ConclusionsThis clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. Trial registrationThe trial is registered at ClinicalTrials.gov (NCT04347330)