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BMC Pulmonary Medicine Mar 2024In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused...
BACKGROUND
In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused enlargement of the heart. The purpose of this study was to collect and analyze case reports on vitamin C and pulmonary hypertension.
METHODS
We searched Pubmed and Scopus for case studies in which vitamin C deficiency was considered to be the cause of pulmonary hypertension. We selected reports in which pulmonary hypertension was diagnosed by echocardiography or catheterization, for any age, sex, or dosage of vitamin C. We extracted quantitative data for our analysis. We used the mean pulmonary artery pressure (mPAP) as the outcome of primary interest.
RESULTS
We identified 32 case reports, 21 of which were published in the last 5 years. Dyspnea was reported in 69%, edema in 53% and fatigue in 28% of the patients. Vitamin C plasma levels, measured in 27 cases, were undetectable in 24 and very low in 3 cases. Diet was poor in 30 cases and 17 cases had neuropsychiatric disorders. Right ventricular enlargement was reported in 24 cases. During periods of vitamin C deficiency, the median mPAP was 48 mmHg (range 29-77 mmHg; N = 28). After the start of vitamin C administration, the median mPAP was 20 mmHg (range 12-33 mmHg; N = 18). For the latter 18 cases, mPAP was 2.4-fold (median) higher during vitamin C deficiency. Pulmonary vascular resistance (PVR) during vitamin C deficiency was reported for 9 cases, ranging from 4.1 to 41 Wood units. PVR was 9-fold (median; N = 5) higher during vitamin C deficiency than during vitamin C administration. In 8 cases, there was direct evidence that the cases were pulmonary artery hypertension (PAH). Probably the majority of the remaining cases were also PAH.
CONCLUSIONS
The cases analyzed in our study indicate that pulmonary hypertension can be one explanation for the reported heart failure of scurvy patients in the early literature. It would seem sensible to measure plasma vitamin C levels of patients with PH and examine the effects of vitamin C administration.
Topics: Humans; Animals; Guinea Pigs; Hypertension, Pulmonary; Scurvy; Pulmonary Arterial Hypertension; Vascular Resistance; Ascorbic Acid Deficiency; Heart Failure; Ascorbic Acid
PubMed: 38504249
DOI: 10.1186/s12890-024-02941-x -
BMJ Open Respiratory Research Mar 2024Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality....
OBJECTIVES
Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality. Pulmonary hypertension may complicate advanced interstitial lung disease (PH-ILD) and is associated with high rates of disability, hospitalisation due to cardiac and respiratory illnesses, and mortality. Prior management hinged on treating the underlying lung disease and comorbidities. However, the INCREASE trial of inhaled treprostinil in PH-ILD has demonstrated that PH-ILD can be effectively treated with vasoactive drugs.
METHODS
This comprehensive systematic review examines the evidence for vasoactive drugs in the management of PH-ILD.
RESULTS
A total of 1442 pubblications were screened, 11 RCTs were considered for quantitative synthesis. Unfortunately, the salient studies are limited by population heterogeneity, short-term follow-up and the selection of outcomes with uncertain clinical significance.
CONCLUSIONS
This systematic review underscores the necessity of establishing a precision medicine-oriented strategy, directed at uncovering and addressing the intricate cellular and molecular mechanisms that underlie the pathophysiology of PH-ILD.
PROSPERO REGISTRATION NUMBER
CRD42023457482.
Topics: Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Comorbidity
PubMed: 38479818
DOI: 10.1136/bmjresp-2023-002161 -
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 -
Cureus Jan 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is underdiagnosed and has recently surfaced as one of the leading triggers of severe pulmonary hypertension. This... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) is underdiagnosed and has recently surfaced as one of the leading triggers of severe pulmonary hypertension. This disease process is described by structural changes of pulmonary arteries such as fibrous stenosis, complete obliteration, or the presence of a resistant intraluminal thrombus, resulting in increased pulmonary resistance and eventually progressing to right-sided heart failure. Hence, this study aims to describe the current treatments for CTEPH and their efficacy in hemodynamic improvement and prevention of recurring thromboembolic episodes in patients. This systematic review promptly follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. On February 13, 2022, our team searched through the following databases: PubMed, ProQuest, and ScienceDirect. The following keywords were used across all databases: CTEPH AND Pulmonary Endarterectomy (PEA), CTEPH AND Balloon Pulmonary Angioplasty (BPA), and CTEPH AND Medical Therapy OR Anticoagulation therapy. Twenty-nine thousand eighty-nine articles on current management techniques (PEA, Balloon angioplasty, anticoagulants) were selected, analyzed, and reviewed with each other. We found 19 articles concerning PEA, 15 concerning BPA, and six regarding anticoagulants. Most papers showed high success rates and promising evidence of PEA and anticoagulants as a post-operative regimen. BPA was the least preferred but is still reputable in patients unfit for invasive techniques. CTEPH is a condition presenting with either fibrous stenosis, complete obliteration of the artery, or a clogged thrombus. Recent studies have shown three techniques that physicians have used to treat CTEPH: balloon-pulmonary angioplasty, PEA, and medical management with anticoagulants. PEA followed by anticoagulants is preferred to balloon pulmonary angioplasties. CTEPH is an ongoing topic in research; as it continues to be researched, we hope to see more management techniques available.
PubMed: 38435894
DOI: 10.7759/cureus.53336 -
Frontiers in Pediatrics 2024Prolonged mechanical ventilation, commonly used to assist preterm newborns, increases the risk of developing bronchopulmonary dysplasia (BPD). In recent decades, studies... (Review)
Review
INTRODUCTION
Prolonged mechanical ventilation, commonly used to assist preterm newborns, increases the risk of developing bronchopulmonary dysplasia (BPD). In recent decades, studies have demonstrated that systemic corticosteroids play a significant role in the prevention and management of BPD. In this systematic review of randomized controlled trials (RCTs), we evaluated the association between the administration of systemic corticosteroids in preterm infants and its long-term outcomes, such as neurodevelopment, growth, extubation rate, and related adverse effects.
METHODS
We conducted an electronic search in Medline, Scopus, and PubMed using the following terms: "premature infants" and "corticosteroids." We considered all RCTs published up to June 2023 as eligible. We included all studies involving preterm newborns treated with systemic corticosteroids and excluded studies on inhaled corticosteroids.
RESULTS
A total of 39 RCTs were evaluated. The influence of steroids administered systemically during the neonatal period on long-term neurological outcomes remains unknown, with no influence observed for long-term growth. The postnatal administration of systemic corticosteroids has been found to reduce the timing of extubation and improve respiratory outcomes. Dexamethasone appears to be more effective than hydrocortisone, despite causing a higher rate of systemic hypertension and hyperglycemia. However, in the majority of RCTs analyzed, there were no differences in the adverse effects related to postnatal corticosteroid administration.
CONCLUSION
Dexamethasone administered during the neonatal period appears to be more effective than hydrocortisone in terms of respiratory outcomes; however, caution should be taken when administering dexamethasone. Data derived from current evidence, including meta-analyses, are inconclusive on the long-term effects of the administration of systemic steroids in preterm infants or the possibility of neurodevelopmental consequences.
PubMed: 38419972
DOI: 10.3389/fped.2024.1344337 -
Children (Basel, Switzerland) Feb 2024This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health,... (Review)
Review
This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.
PubMed: 38397319
DOI: 10.3390/children11020208 -
Internal and Emergency Medicine Apr 2024The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of... (Meta-Analysis)
Meta-Analysis
The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.
Topics: Humans; Antihypertensive Agents; Connective Tissue Diseases; Peptide Fragments; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic
PubMed: 38378970
DOI: 10.1007/s11739-024-03539-1 -
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 -
Journal of Scleroderma and Related... Feb 2024Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines...
BACKGROUND AND OBJECTIVE
Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines recommend annual screening for PAH regardless of symptoms, as early treatment improves outcomes. Current protocols include combinations of clinical features, biomarkers, pulmonary function tests, and echocardiography. None include exercise testing, although early-stage PAH may only be evident during exercise. This systematic review assessed the performance of exercise tests in predicting the presence of PAH in patients with SSc, where PAH was confirmed through right heart catheterisation (RHC).
METHODS
Comprehensive literature searches were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trails, CINAHL, Scopus and Web of Science from inception to May 2023. Articles were screened for eligibility by two independent reviewers. Eligibility criteria included the use of a non-invasive exercise test to screen adult patients to detect PAH in a population without a previous diagnosis of PAH, with diagnosis confirmed by RHC.
RESULTS
Eight studies met the inclusion criteria, describing at least one of three different non-invasive exercise tests: cardiopulmonary exercise test, six-minute walk test and stress Doppler echocardiography. All studies found that exercise tests had some ability to predict the presence of PAH, with sensitivity between 50% and 100% and specificity from 73% to 91%.
CONCLUSION
Exercise tests are infrequently used for screening for PAH in SSc but can predict the presence of PAH. More data are required to establish which tests are most effective.
PubMed: 38333530
DOI: 10.1177/23971983231199148 -
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