Abstract Background Heart failure with reduced ejection fraction (HFrEF) is the global public health burden with a prevalence of 1% of adults. The current guidelines suggest the use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce mortality. Soluble guanylyl cyclase (sGC) and omecamtiv mecarbil (OMM) have also been studied in HFrEF. However, there has been no head-to-head comparison of the efficacy and cumulative incidence interpretation of the outcome of the novel drugs. Purpose To compare all drugs and possible combinations of guideline-directed medical therapy (GDMT) including ACEI, ARB, BB, and MRA, and novel drugs including ivabradine (IVA), ARNI, SGLT2i, sGC and OMM to find the best additional novel drug to the GDMT. Methods This network meta-analysis (MA) is part of the study registered on PROSPERO (CRD42021262029). A systematic search of MAs and randomised controlled trials (RCT) was performed on biomedical databases from inception to June 2021. All MAs and RCTs were selected against eligibility criteria. A primary composite outcome or a composite of cardiovascular death or heart failure hospitalisation was the outcome of focus. In addition, secondary outcomes, i.e., cardiovascular death and heart failure hospitalisation were analysed. Individual patient data was constructed from Kaplan-Meier-extracted data; then data from all studies were combined. A mixed-effect parametric survival model with accelerated failure time was used, considering individual study as random effects and treatments as a fixed-effect. Median failure time for each regimen and hazard ratios (HR) comparing between regimens with 95% confidence intervals (CI) were then estimated from KM data. Results Cumulative incidence of the primary outcome from each regimen is displayed in Figure 1. Compared to the GDMT or ACEI+BB+MRA, BB+MRA+ARNI (HR 0.80, 95% CI 0.74–0.88), ACEI+BB+MRA+IVA (HR 0.82, 95% CI 0.75–0.90), ACEI+BB+MRA+SGLT2i (HR 0.75, 95% CI 0.68–0.82), ACEI+BB+MRA+sGC (HR 0.91, 95% CI 0.83–0.99), and ACEI+BB+MRA+OMM (HR 0.92, 95% CI 0.86–0.99) showed superior benefits. However, ACEI+BB (HR 0.68, 95% CI 0.59–0.79) and ACEI+BB+ARB (HR 0.81, 95% CI 0.67–0.98) were both statistically significantly inferior to the GDMT. The treatment combination of ACEI+BB+MRA+SGLT2i showed the highest risk reduction of 25%. More details are provided in Figure 2. The analysis of secondary outcomes showed a corresponding trend with ACEI+BB+MRA+SGLT2i combination reducing the risk of cardiovascular death by 25% (HR 0.75, 95% CI 0.68–0.82) and heart failure hospitalisation by 25% (HR 0.75, 95% CI 0.68–0.82) versus the GDMT. Conclusion The network MA showed that the SGT2i is currently the best additional drug to the GDMT in the treatment of HFrEF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Faculty of Medicine Ramathibodi Hospital, Mahidol University
Conclusiones de los autores del estudio: indometacina o ibuprofeno, administrados a prematuros mayores de un dia de vida, favorecen el cierre del conducto arterioso pero no se han observado otros beneficios a corto plazo. El tratamiento con ibuprofeno puede incrementar el riesgo de enfermedad pulmonar cronica.
Comentario de los revisores: ambos farmacos son eficaces para el cierre del conducto arterial persistente, pero la eleccion entre uno u otro dependera de criterios de seguridad, teniendo en cuenta que el ibuprofeno parece relacionarse con mayor incidencia de enfermedad pulmonar cronica y la indometacina con mayor oliguria.
To evaluate the effects of indomethacin or ibuprofen compared with placebo on closure, morbidity and mortality in preterm infants <37 weeks9 gestation with echocardiographically and/or clinically important patent ductus arteriosus (PDA) at >24 h of life.
Data sources
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Cochrane Library, clinicaltrials.gov, controlled-trials.com, American Pediatric and European Paediatric Research Societies and Effective Care of the Newborn Infant.
Review methods
Systematic review with network meta-analysis of randomised studies comparing intravenous indomethacin, ibuprofen or placebo for PDA in preterm infants at >24 h of life.
Results
Ten trials compared intravenous indomethacin versus intravenous ibuprofen, nine intravenous indomethacin versus placebo and one intravenous ibuprofen versus placebo. Both intravenous indomethacin (pooled RR 2.39 (95% CI 2.05 to 2.78)) and intravenous ibuprofen (RR 2.40 (95% CI 2.03 to 2.84)) closed a PDA more effectively than placebo. Intravenous ibuprofen was associated with approximately 30% greater risk of chronic lung disease than intravenous indomethacin (RR 1.28 (95% CI 1.03 to 1.60)) or placebo (RR 1.29 (95% CI 0.99 to 1.70)). Differences in risk or benefit were not significant between any combination of intravenous indomethacin, intravenous ibuprofen or placebo groups for intraventricular haemorrhage, necrotising enterocolitis and death. Reporting on neurological outcomes was insufficient for pooling.
Conclusions
Intravenous indomethacin or ibuprofen administered to preterm infants for PDA at >24 h of life promoted ductal closure, but other short-term benefits were not seen. Treatment with intravenous ibuprofen may increase the risk of chronic lung disease. Good-quality evidence of treatment effect on morbidity, mortality and improved neurodevelopment is urgently needed.
To determine survival among patients with epithelial ovarian carcinoma (EOC) who underwent a second-look laparotomy (SLL) and those refusing the procedure. Also to analyze factor(s) influencing the survival of the patients.Medical records were reviewed of patients with advanced EOC who were clinically free of disease after primary surgery and platinum-based chemotherapy between January 1, 1992, and December 31, 1998. All of them were offered SLL. Measurement outcomes include patient survival and disease-free survival.There were 50 patients with clinically complete remission after chemotherapy. Sixteen patients underwent SLL, and thirty-four patients refused the procedure (NSLL). Seven patients (43.8%) were reported to have positive SLL. After the median follow-up time of 35 months, 12 patients had died, and 5 patients were lost to follow-up. The median survival time for patients with SLL was about 60 months. Five-year survival rates of patients in the SLL, and NSLL groups were 37 per cent (95%CI = 7%-69%), and 88 per cent (95%CI = 65%-96%) respectively (P<0.001). The median time to relapse was about 25 months for patients with negative SLL. Five-year disease-free survival rates of patients in the negative SLL, and NSLL groups were 28 per cent (95%CI = 4%-59%), and 54 per cent (95%CI = 34%-70%) respectively (P=0.251). By Cox regression analysis, tumor grade was the only significant prognostic factor influencing patients' survival (HR = 6, 95%CI of HR = 1.2-34.2).The second-look laparotomy doesn't have a favorable impact on overall and disease-free survival. Tumor grade is the only independent prognostic variable for survival of the patients.
Abstract Background: We set out to review the validity of tests for B type natriuretic peptide (BNP) and N‐terminal pro BNP (NTproBNP) in the diagnosis of clinical heart failure (HF) in primary care and hospital settings and to examine the effect of age. We also examined the accuracy of the test in population screening for left ventricular systolic dysfunction. Methods: Medline and Embase were searched systematically till June 2005. Forty‐seven studies were identified for systematic review and 27 were included in meta‐analyses. Test performance was summarized as the diagnostic odds ratio (DOR). As a secondary data analysis, this paper does not require ethical approval. Results: In groups of symptomatic patients with average age less than 80 years, the summary DOR of 27 for BNP equates to a sensitivity of 85% and specificity of 84% in the detection of clinical HF. Summary of head‐to‐head studies shows BNP is a better indicator than NTproBNP. The performance of both tests decreased with the age of patients, the DOR declining by a factor of 2.0 for BNP and 2.5 for NTproBNP for each decade of increasing age. BNP correlated better to clinical status than to echocardiographic parameters, and test performance was similar in acute inpatient and general practice settings. Conclusion: Tests for BNP are helpful in the diagnosis of clinical HF or in screening for left ventricular systolic dysfunction and are superior to NTproBNP. In the clinical setting, test performance declined with increasing patient age.
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