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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 -
Open Heart Feb 2024Right ventricular (RV) dysfunction is associated with adverse outcomes in patients with pulmonary hypertension (PH). This systematic review and meta-analysis evaluated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Right ventricular (RV) dysfunction is associated with adverse outcomes in patients with pulmonary hypertension (PH). This systematic review and meta-analysis evaluated the prognostic value of RV free-wall longitudinal strain (RVfwLS), compared with other RV parameters in PH.
METHODS
We searched for articles presenting the HR of two-dimensional RVfwLS in PH. HRs were standardised using the within-study SD. The ratio of HRs of a 1 SD change in RVfwLS versus systolic pulmonary arterial pressure (SPAP), systolic tricuspid annular velocities (s'-TV), RV fractional area change (FAC) or tricuspid annular plane systolic excursion (TAPSE) was calculated for each study, after which we conducted a random model meta-analysis. Subgroup analysis regarding the type of outcome, aetiology of PH and software vendor was also performed.
RESULTS
Twenty articles totalling 2790 subjects were included. The pooled HR of a 1 SD decrease of RVfwLS was 1.80 (95% CI: 1.62 to 2.00, p<0.001), and there was a significant association with all-cause death (ACD) and composite endpoints (CEs). The ratio of HR analysis revealed that RVfwLS has a significant, strong association with ACD and CE per 1 SD change, compared with corresponding values of SPAP, s'-TV, RVFAC or TAPSE. RVfwLS was a significant prognostic factor regardless of the aetiology of PH. However, significant superiority of RVfwLS versus other parameters was not observed in group 1 PH.
CONCLUSIONS
The prognostic value of RVfwLS in patients with PH was confirmed, and RVfwLS is better than other RV parameters and SPAP. Further accumulation of evidence is needed to perform a detailed subgroup analysis for each type of PH.
TRIAL REGISTRATION NUMBER
UMIN Clinical Trials Registry (UMIN000052679).
Topics: Humans; Prognosis; Hypertension, Pulmonary; Tricuspid Valve; Systole
PubMed: 38325907
DOI: 10.1136/openhrt-2023-002561 -
ESC Heart Failure May 2024A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation...
AIMS
A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta-analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies.
METHODS AND RESULTS
According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta-analyses. Data were extracted and curated for Bayesian network meta-analysis. The primary outcome was the change in the 6-min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (-77.76 m, 95% CI: -102.04 to -54.34 m), Macitentan (-65.32 m, 95% CI: -95.34 to -36.1 m), Bosentan (-64.5 m, 95% CI: -94.7 to -35.07 m), Iloprost (-62.66 m, 95% CI: -99.48 to -27.13 m), Oxygen (-62.42 m, 95% CI: -100.01 to -25.78 m), Treprostinil (-62.01 m, 95% CI: -89.04 to -35.61 m), Riociguat (-60.59 m, 95% CI: -86.11 to -35.98 m), Selexipag (-47.2 m, 95% CI: -85.61 to -10.19 m), Sildenafil (-44.92 m, 95% CI: -74.43 to -16.15 m), or Sitaxsentan (-39.53 m, 95% CI: -78.99 to -0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re-hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions.
CONCLUSIONS
Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual-drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.
PubMed: 38783684
DOI: 10.1002/ehf2.14842 -
Clinical Research in Cardiology :... Aug 2023Congestion is a key driver of morbidity and mortality in heart failure. Implanted haemodynamic monitoring devices might allow early identification and management of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Congestion is a key driver of morbidity and mortality in heart failure. Implanted haemodynamic monitoring devices might allow early identification and management of congestion. Here, we provide a state-of-the-art review of implanted haemodynamic monitoring devices for patients with heart failure, including a meta-analysis of randomised trials.
METHODS AND RESULTS
We did a systematic search for pre-print and published trials in Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) on the 22nd of September 2021. We included randomised trials that compared management with or without information from implanted haemodynamic monitoring devices for patients with heart failure. Outcomes selected were hospitalisation for heart failure and all-cause mortality. Changes in treatment associated with haemodynamic monitoring resulted in only a small reduction in mean pulmonary artery pressure (typically < 1 mmHg as a daily average), which generally remained much greater than 20 mmHg. Haemodynamic monitoring reduced hospitalisations for heart failure (HR 0.75; 95% CI 0.58-0.96; p = 0.03) but not mortality (RR 0.92; 95% CI 0.68-1.26; p = 0.48).
CONCLUSIONS
Haemodynamic monitoring for patients with heart failure may reduce the risk of hospitalization for heart failure but this has not yet translated into a reduction in mortality, perhaps because the duration of trials was too short or the reduction in pulmonary artery pressure was not sufficiently large. The efficacy and safety of aiming for larger reductions in pulmonary artery pressure should be explored. After selecting key words, a systematic review for implanted haemodynamic telemonitoring devices was performed in different dataset and 4 randomised clinical trials were identified and included in this meta-analysis. Three different devices (Chronicle, Chronicle/ICD and CardioMEMS) were tested. All-cause mortality and total heart failure hospitalisations were selected as outcomes. No reduction in all-cause mortality rate was reported but a potential benefit on total heart failure hospitalisation was identified.
Topics: Humans; Heart Failure; Hemodynamics; Hospitalization; Monitoring, Physiologic; Randomized Controlled Trials as Topic
PubMed: 36241896
DOI: 10.1007/s00392-022-02104-0 -
Journal of the American Heart... Jun 2024In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of...
BACKGROUND
In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target.
METHODS AND RESULTS
Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification. Observational studies and clinical trials describing risk stratification at both baseline and follow-up were included. Sixty five studies were eligible for inclusion, including only 2 studies in a pediatric population. C-statistic range at baseline was 0.31 to 0.77 and improved to 0.30 to 0.91 at follow-up. In 53% of patients, risk status changed (42% improved, 12% worsened) over 168 days (interquartile range, 137-327 days; n=22 studies). The average proportion of low-risk patients increased from 18% at baseline to 36% at a median follow-up of 244 days (interquartile range, 140-365 days; n=40 studies). In placebo-controlled drug studies, risk statuses of the intervention groups improved more and worsened less compared with the placebo groups. Furthermore, a low-risk status, but also an improved risk status, at follow-up was associated with a better outcome. Similar results were found in the 2 pediatric studies.
CONCLUSIONS
Follow-up risk stratification has improved prognostic value compared with baseline risk stratification, and change in risk status between baseline and follow-up corresponded to a change in survival. These data support the use of serial risk stratification as treatment target in pulmonary arterial hypertension.
PubMed: 38904230
DOI: 10.1161/JAHA.123.034151 -
Thrombosis Research Jun 2024COVID-19 has disproportionately affected racialized populations, with particular impact among individuals of Black individuals. However, it is unclear whether... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
COVID-19 has disproportionately affected racialized populations, with particular impact among individuals of Black individuals. However, it is unclear whether disparities in venous thromboembolic (VTE) complications exist between Black individuals and those belonging to other racial groups with confirmed SARS-CoV2 infections.
OBJECTIVE
To summarize the prevalence and moderators associated with VTE among Black COVID-19 patients in minoritized settings, and to compare this to White and Asian COVID-19 patients according to sex, age, and comorbid health conditions (heart failure, cancer, obesity, hypertension).
DESIGN SETTING, AND PARTICIPANTS
A systematic search of MEDLINE, Embase, CINAHL and CENTRAL for articles or reports published from inception to February 15, 2023.
STUDY SELECTION
Reports on VTE among Black individuals infected with SARS-CoV2, in countries where Black people are considered a minority population group.
DATA EXTRACTION AND SYNTHESIS
Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers. VTE prevalence was extracted, and risk of bias was assessed. Prevalence estimates of VTE prevalence among Black individuals with COVID19 in each study were pooled. Where studies provided race-stratified VTE prevalence among COVID19 patients, odds ratios were generated using a random-effects model.
MAIN OUTCOMES AND MEASURES
Prevalence of VTE, comprising of deep vein thrombosis and pulmonary embolism.
RESULTS
Ten studies with 66,185 Black individuals reporting the prevalence of COVID-19 associated VTE were included. Weighted median age of included studies was 47.60. Pooled prevalence of COVID-19 associated VTE was 7.2 % (95 % CI, 3.8 % - 11.5 %) among Black individuals. Among individuals with SARS-CoV2 infections, Black population had higher risks of VTE compared to their White (OR = 1.79, [95 % CI 1.28-2.53], p < .001) or Asian (OR = 2.01, [95 % CI, 1.14-3.60], p = .017) counterparts, or patients with other racial identities (OR = 2.01, [95 % CI, 1.39, 2.92]; p < .001).
CONCLUSIONS AND RELEVANCE
Black individuals with COVID-19 had substantially higher risk of VTE compared to White or Asian individuals. Given racial disparities in thrombotic disease burden related to COVID-19, medical education, research, and health policy interventions are direly needed to ensure adequate disease awareness among Black individuals, to facilitate appropriate diagnosis and treatment among Black patients with suspected and confirmed VTE, and to advocate for culturally safe VTE prevention strategies, including pre-existing inequalities to the COVID-19 pandemic that persist after the crisis.
Topics: Humans; COVID-19; Venous Thromboembolism; White People; Prevalence; SARS-CoV-2; Asian People; Female; Male; Risk Factors; Minority Groups; Black People
PubMed: 38733691
DOI: 10.1016/j.thromres.2024.05.007 -
Critical Care Explorations Feb 2024Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS)... (Review)
Review
OBJECTIVES
Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality.
DATA SOURCES
Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023.
STUDY SELECTION
Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included.
DATA EXTRACTION
Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses.
DATA SYNTHESIS
Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18-0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71-2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24-6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19-1.8). However, the certainty of evidence for most outcomes was low to very low.
CONCLUSIONS
While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.
PubMed: 38352941
DOI: 10.1097/CCE.0000000000001054 -
Frontiers in Immunology 2024The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is... (Meta-Analysis)
Meta-Analysis
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis.
INTRODUCTION
The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group.
METHODS
We conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools.
RESULTS
In 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p<0.001; I = 74.5%, p<0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p<0.001; I = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I = 87.6%, p<0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p<0.001; I = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001).
DISCUSSION
Pending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.
Topics: Humans; Scleroderma, Systemic; Neutrophils; Lymphocytes; Monocytes; Blood Platelets; Lymphocyte Count; Biomarkers; Platelet Count
PubMed: 38799443
DOI: 10.3389/fimmu.2024.1395993 -
Heart Failure Reviews Jan 2024The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right... (Meta-Analysis)
Meta-Analysis
The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.
Topics: Humans; Echocardiography, Doppler; Heart Failure; Hypertension, Pulmonary; Prognosis; Prospective Studies; Pulmonary Artery; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right
PubMed: 37639067
DOI: 10.1007/s10741-023-10341-2 -
Annals of Internal Medicine Apr 2024There is increasing concern for the potential impact of health care algorithms on racial and ethnic disparities. (Review)
Review
BACKGROUND
There is increasing concern for the potential impact of health care algorithms on racial and ethnic disparities.
PURPOSE
To examine the evidence on how health care algorithms and associated mitigation strategies affect racial and ethnic disparities.
DATA SOURCES
Several databases were searched for relevant studies published from 1 January 2011 to 30 September 2023.
STUDY SELECTION
Using predefined criteria and dual review, studies were screened and selected to determine: 1) the effect of algorithms on racial and ethnic disparities in health and health care outcomes and 2) the effect of strategies or approaches to mitigate racial and ethnic bias in the development, validation, dissemination, and implementation of algorithms.
DATA EXTRACTION
Outcomes of interest (that is, access to health care, quality of care, and health outcomes) were extracted with risk-of-bias assessment using the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool and adapted CARE-CPM (Critical Appraisal for Racial and Ethnic Equity in Clinical Prediction Models) equity extension.
DATA SYNTHESIS
Sixty-three studies (51 modeling, 4 retrospective, 2 prospective, 5 prepost studies, and 1 randomized controlled trial) were included. Heterogenous evidence on algorithms was found to: a) reduce disparities (for example, the revised kidney allocation system), b) perpetuate or exacerbate disparities (for example, severity-of-illness scores applied to critical care resource allocation), and/or c) have no statistically significant effect on select outcomes (for example, the HEART Pathway [history, electrocardiogram, age, risk factors, and troponin]). To mitigate disparities, 7 strategies were identified: removing an input variable, replacing a variable, adding race, adding a non-race-based variable, changing the racial and ethnic composition of the population used in model development, creating separate thresholds for subpopulations, and modifying algorithmic analytic techniques.
LIMITATION
Results are mostly based on modeling studies and may be highly context-specific.
CONCLUSION
Algorithms can mitigate, perpetuate, and exacerbate racial and ethnic disparities, regardless of the explicit use of race and ethnicity, but evidence is heterogeneous. Intentionality and implementation of the algorithm can impact the effect on disparities, and there may be tradeoffs in outcomes.
PRIMARY FUNDING SOURCE
Agency for Healthcare Quality and Research.
Topics: Humans; Retrospective Studies; Prospective Studies; Healthcare Disparities; Ethnicity; Quality of Health Care
PubMed: 38467001
DOI: 10.7326/M23-2960