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Resuscitation Plus Jun 2023To perform a systematic review of administration of calcium compared to no calcium during cardiac arrest. (Review)
Review
AIM
To perform a systematic review of administration of calcium compared to no calcium during cardiac arrest.
METHODS
The search included Medline (PubMed), Embase, Cochrane, Web of Science, and CINAHL Plus and was conducted on September 30, 2022. The population included adults and children in any setting with cardiac arrest. The outcomes included return of spontaneous circulation, survival, survival with favourable neurologic outcome to hospital discharge and 30 days or longer, and quality of life outcome. Cochrane Risk of Bias 2 and ROBINS-I were performed to assess risk of bias for controlled and observational studies, respectively.
RESULTS
The systematic review identified 4 studies on 3 randomised controlled trials on 554 adult out-of-hospital cardiac arrest (OHCA) patients, 8 observational studies on 2,731 adult cardiac arrest patients, and 3 observational studies on 17,449 paediatric in-hospital cardiac arrest (IHCA) patients. The randomised controlled and observational studies showed that routine calcium administration during cardiac arrest did not improve the outcome of adult OHCA or IHCA or paediatric IHCA. The risk of bias for the adult trials was low for one recent trial and high for two earlier trials, with randomization as the primary source of bias. The risk of bias for the individual observational studies was assessed to be critical due to confounding. The certainty of evidence was assessed to be moderate for adult OHCA and low for adult and paediatric IHCA. Heterogeneity across studies precluded any meaningful meta-analyses.
CONCLUSIONS
This systematic review found no evidence that routine calcium administration improves the outcomes of cardiac arrest in adults or children.PROSPERO Registration: CRD42022349641.
PubMed: 37025978
DOI: 10.1016/j.resplu.2023.100379 -
Pulmonary Circulation 2020Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary...
Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review.
Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.
PubMed: 33088478
DOI: 10.1177/2045894020948780 -
Journal of Applied Physiology... Dec 2017Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic...
Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension (PH), exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange, and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects, as well as in patients with PH, maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH patients, these improvements were mediated by a better arterial, muscular, and cerebral oxygenation, along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with PH, alterations in the inspiratory Po by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control, and by alterations in pulmonary gas exchange. The understanding of these physiological mechanisms helps in counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with PH.
Topics: Altitude; Exercise; Humans; Hyperoxia; Hypertension, Pulmonary; Hypoxia; Oxygen Consumption; Pulmonary Gas Exchange
PubMed: 28775065
DOI: 10.1152/japplphysiol.00186.2017 -
Frontiers in Pharmacology 2023Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach...
Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients. Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated. Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70-43.2 m, = 0.002) and improved mPAP (WMD = -3.53, 95% CIs: -5.62-1.44 mmHg, = 0.0009), PVR (WMD = -130.24 dyn·s·cm, 95% CI -187.43-73.05, 0.0001), CIs (WMD = 0.36 L/min·cm, 95% CIs: 0.25-0.47, 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08-0.16, < 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is. PAH patients benefit from PDE-5is compared to riociguat, including in hemodynamic parameters, 6MWD, WHO-FC and biomarkers.
PubMed: 36778016
DOI: 10.3389/fphar.2023.1052546 -
Animal Models and Experimental Medicine Feb 2024The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta-analysis.
METHODS
Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO), were included.
RESULTS
Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74-37.67), NT-proBNP (SMD: -0.41, 95% CI: -0.79-0.04), CI (MD: 0.47 L/min/m, 95% CI: 0.17-0.77) and WHO-FC (OR: 0.564, 95% CI: 0.457-0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m, 95% CI: 0.15-0.46) and WHO-FC (OR: 0.589, 95% CI: 0.376-0.922). Within 6 months of treatment, only the WHO-FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380-0.993; MD: 0.30 L/min/m, 95% CI: 0.16-0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO-FC and NT-proBNP (MD: 40.87 m, 95% CI: 10.97-70.77; OR: 0.557, 95% CI: 0.440-0.705; SMD: -0.61, 95% CI: -1.17-0.05, respectively).
CONCLUSIONS
Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low-dosage group. This finding is important for guiding individualized treatments.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Acetamides; Pyrazines
PubMed: 37740617
DOI: 10.1002/ame2.12347 -
The Annals of Thoracic Surgery Jul 2014A clear consensus regarding the optimal source of pulmonary blood flow in patients with hypoplastic left heart syndrome undergoing the Norwood procedure is lacking. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A clear consensus regarding the optimal source of pulmonary blood flow in patients with hypoplastic left heart syndrome undergoing the Norwood procedure is lacking.
METHODS
A literature search was undertaken to identify relevant articles from 2005 to 2012 using "Norwood, stage 1 palliation," "Modified Blalock Taussig shunt (MBTS)," "right ventricle-to-pulmonary artery shunt (RV-PAS)" alone or in combination. Three end points were selected: early/stage 1 mortality, interstage mortality, and interstage total/shunt intervention.
RESULTS
A total of 20 articles, including 19 observational studies and 1 randomized trial (MBTS, n=1,343; RV-PAS, n=1,028), met the inclusion criteria. Mortality after stage 1 was 22% in the MBTS cohort and 16% in RV-PAS cohort. A pooled analysis showed no difference in early mortality between the two groups (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99 to 1.45; p=0.07). On pooling data from contemporary series (similar era) of 8 studies (MBTS, n=709; RV-PAS, n=631), to minimize variability in surgical and postoperative management practices, early mortality in both cohorts was comparable (RR, 1.14; 95% CI, 0.89 to 1.45; p=0.29). Interstage mortality was 13.8% and 4.6% in the MBTS and RV-PAS cohorts, respectively, and was significantly lower for RV-PAS (RR, 2.85; 95% CI, 1.65 to 4.89; p<0.00002). However, patients with MBTS had fewer shunt interventions (RR, 0.55; 95% CI, 0.44 to 0.68; p<0.001; I2=00%).
CONCLUSIONS
Our pooled analysis demonstrated no survival benefit for the MBTS or RV-PAS in patients undergoing the Norwood procedure. There appears to be an advantage with the RV-PAS with regard to interstage mortality at the cost of an increased rate of shunt intervention.
Topics: Global Health; Heart Ventricles; Humans; Hypoplastic Left Heart Syndrome; Norwood Procedures; Pulmonary Artery; Pulmonary Circulation; Regional Blood Flow; Survival Rate; Treatment Outcome
PubMed: 24793687
DOI: 10.1016/j.athoracsur.2014.02.078 -
Thrombosis Research Mar 2014According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.
MATERIAL AND METHOD
We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.
RESULTS
Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50mg or 50mg infusion 2h) with standard dose (100mg infusion 2h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P=0.94,I(2)=0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50mg/2 min bolus or 10mg bolus, ≤40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P=0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.
CONCLUSIONS
The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn't increase the risk of major bleeding for eligible PE patients.
Topics: Dose-Response Relationship, Drug; Humans; Pulmonary Embolism; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 24412030
DOI: 10.1016/j.thromres.2013.12.026 -
Reproductive Toxicology (Elmsford, N.Y.) Nov 2012An association between PPHN and antidepressant use in pregnancy has been reported. (Review)
Review
BACKGROUND
An association between PPHN and antidepressant use in pregnancy has been reported.
PURPOSE
We sought to examine this relationship.
METHODS
A review of the literature was performed, to evaluate this association.
RESULTS
Six published studies fulfilled our criteria for inclusion, with only three studies large enough to have the power to detect an association. There appears to be a small but significantly, increased risk of late pregnancy SSRI exposure associated with PPHN in one case-control study; OR 5.1 (95% CI, 1.9-13.3) and two large cohort studies; RR 2.56; (95% CI, 1.17-4.85) and OR 2.1 (95% CI, 1.5-3.0) The other three studies did not find an association.
CONCLUSION
the absolute risk cannot be determined, but it is very small, probably less than 1%. If a pregnant woman requires pharmacological treatment, this information does not support discontinuation or lowering the dose of the antidepressant.
Topics: Antidepressive Agents; Female; Humans; Infant, Newborn; Persistent Fetal Circulation Syndrome; Pregnancy; Selective Serotonin Reuptake Inhibitors
PubMed: 22564982
DOI: 10.1016/j.reprotox.2012.04.015 -
Circulation Aug 2022Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for... (Meta-Analysis)
Meta-Analysis
Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to December 2020) for trials evaluating the effects of PAH therapies on CW. The coefficient of determination between the RR for CW and mortality was assessed by regression analysis. The frequency of occurrence, RR reduction, and importance to patients of the CW components were assessed.
RESULTS
We included 35 independent cohorts (9450 patients). PAH therapies significantly reduced CW events (RR, 0.64 [95% CI, 0.55-0.73]), including PAH-related hospitalizations (RR, 0.61 [95% CI, 0.47-0.79]), treatment escalation (RR, 0.57 [95% CI, 0.38-0.84]) and symptomatic progression (RR, 0.58 [95% CI, 0.48-0.69]), and modestly reduced all-cause mortality when incorporating deaths occurring after a primary CW-defining event (RR, 0.860 [95% CI, 0.742-0.997]). However, the effects of PAH-specific therapies on CW only modestly correlated with their effects on mortality (, 0.35 [95% CI, 0.10-0.59]; <0.0001), and the gradient in the treatment effect across component end points was large in the majority of trials. The weighted proportions of CW-defining events were hospitalization (33.5%) and symptomatic progression (32.3%), whereas death (6.7%), treatment escalation (5.6%), and transplantation/atrioseptostomy (0.2%) were infrequent. CW events were driven by the occurrence of events of major (49%) and mild-to-moderate (37%) importance to patients, with 14% of the events valued as critical.
CONCLUSIONS
PAH therapies significantly reduced CW events, but study-level CW is not a surrogate for mortality in PAH trials. Moreover, components of CW largely vary in frequency, response to therapy, and importance to patients and are thus not interchangeable.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42020178949.
Topics: Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic; Regression Analysis
PubMed: 35862151
DOI: 10.1161/CIRCULATIONAHA.121.058635 -
Cardiovascular Pathology : the Official... 2016The most significant cardiovascular anatomoclinical observations from Morgagni's masterpiece De sedibus et causis morborum per anatomen indagatis (1761) are herein... (Review)
Review
The most significant cardiovascular anatomoclinical observations from Morgagni's masterpiece De sedibus et causis morborum per anatomen indagatis (1761) are herein reported, divided into the current taxonomy according to cardiac structure: (a) aorta and pulmonary artery, (b) pericardium, (c) coronary arteries, (d) myocardium, (e) endocardium, (f) congenital heart defects, and (g) heart rhythm disorders. Morgagni's interpretations in cardiovascular pathology were strictly related with the most advanced theories of his time, such as those of blood circulation and iatromechanics; nevertheless, he remained close to the empirical description of clinical and pathological anatomy phenomena with their individual specificity. Through a systematic review of the literature, he compared the data from his own observations and experiments with those from physicians he considered reliable by applying the method of literature review which is still valid nowadays.
Topics: Cardiology; Cardiovascular System; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, Medieval; Humans; Medical Illustration; Pathology
PubMed: 27611360
DOI: 10.1016/j.carpath.2016.07.004