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JACC. Advances Feb 2024Antithrombotic therapy (ATT) in patients with infective endocarditis (IE) is challenging.
BACKGROUND
Antithrombotic therapy (ATT) in patients with infective endocarditis (IE) is challenging.
OBJECTIVES
The authors evaluated the impact of anticoagulant and antiplatelet therapy on clinical endpoints in IE patients.
METHODS
We performed a systematic review and meta-analysis comparing IE patients with prior and/or ongoing use of ATT vs those without any ATT during IE course. Primary outcome was reported in-hospital cerebrovascular events. Secondary outcomes were in-hospital mortality, intracranial hemorrhage (ICH), systemic thromboembolism (ST), and mortality within 6 months.
RESULTS
Twelve studies, with a total of 12,151 patients, were included. The primary endpoint was not different comparing 10,115 IE patients with or without prior anticoagulation (OR: 1.10; 95% CI: 0.56-2.17; = 0.77) or comparing 838 IE patients with or without prior antiplatelet (OR: 0.90; 95% CI: 0.61-1.33; = 0.61). In-hospital mortality was lower in IE patients with prior anticoagulation compared to those without (OR: 0.74; 95% CI: 0.57-0.96; = 0.03). There was no difference in reported ICH rates between patients with or without prior anticoagulation (OR: 0.54; 95% CI: 0.27-1.09; = 0.09) or between patients with or without prior antiplatelet (OR: 0.35; 95% CI: 0.11-1.10; = 0.07). The rate of ST was lower in IE patients with prior antiplatelet therapy compared to those without (OR: 0.53; 95% CI: 0.38-0.72; < 0.01).
CONCLUSIONS
ATT in IE patients was not associated with higher frequency of cerebrovascular events or ICH. Moreover, we found that the use of anticoagulation was associated with decreased in-hospital mortality and the use of antiplatelets was associated with decreased ST. Due to the limitations of this study, these results should be interpreted cautiously showing the necessity of a randomized setup.
PubMed: 38939390
DOI: 10.1016/j.jacadv.2023.100768 -
JACC. Advances Feb 2024Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the...
BACKGROUND
Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency.
OBJECTIVES
The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF.
METHODS
We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots.
RESULTS
Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression.
CONCLUSIONS
Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.
PubMed: 38939376
DOI: 10.1016/j.jacadv.2023.100765 -
Przeglad Gastroenterologiczny 2024Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this... (Review)
Review
Safety and efficacy of Single-Pass Albumin Dialysis (SPAD), Prometheus, and Molecular Adsorbent Recycling System (MARS) liver haemodialysis vs. Standard Medical Therapy (SMT): meta-analysis and systematic review.
INTRODUCTION
Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned.Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction.
MATERIAL AND METHODS
PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment.
RESULTS
Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; = 0.31, respectively).
CONCLUSIONS
MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events.
PubMed: 38939063
DOI: 10.5114/pg.2024.139297 -
JACC. Advances Jul 2023Coarctation of the aorta (CoA) is associated with intracranial aneurysms (IAs); however, the prevalence and risk factors (RFs) are not well described. Current practice...
BACKGROUND
Coarctation of the aorta (CoA) is associated with intracranial aneurysms (IAs); however, the prevalence and risk factors (RFs) are not well described. Current practice guidelines offer inconsistent recommendations on screening for IAs in this patient population ranging from "not recommended" (European Society of Cardiology 2020) to "recommended" (American Heart Association 2018).
OBJECTIVES
The purpose of this study was to determine the prevalence and RFs for IAs in patients with CoA.
METHODS
We completed a systematic review and meta-analysis of studies utilizing computed tomography or magnetic resonance angiographic screening for IAs in patients with CoA.
RESULTS
Five cohort studies were included, representing 442 patients. The pooled prevalence of IAs in patients with CoA was 3.8% [95% CI: 0.1%-12.3%]. The results met our prespecified definition for high heterogeneity. Of 5 RFs evaluated, only hypertension was associated with the development of IAs with an odds ratio of 3.1 [95% CI: 1.1-8.2; = 0.03]. There was an observed downward trend over time in the prevalence of IAs among the studies included.
CONCLUSIONS
The development of IAs is likely multifactorial in etiology and there may be modifiable RFs in their development. Considering the low prevalence of IAs in the pooled result, routine screening of patients with CoA for IAs is likely of low-value.
PubMed: 38938992
DOI: 10.1016/j.jacadv.2023.100394 -
Frontiers in Cardiovascular Medicine 2024This meta-analysis aimed to explore the association between serum uric acid levels and the efficacy of uric acid-lowering therapies on clinical outcomes among patients...
Relationship between serum uric acid levels and uric acid lowering therapy with the prognosis of patients with heart failure with preserved ejection fraction: a meta-analysis.
AIMS
This meta-analysis aimed to explore the association between serum uric acid levels and the efficacy of uric acid-lowering therapies on clinical outcomes among patients with heart failure with preserved ejection fraction (HFpEF).
METHODS
A comprehensive literature search was conducted through October 21, 2023, across PubMed, Embase, Cochrane Library, and Web of Science databases. The pooled effect sizes were estimated and presented with their respective 95% confidence intervals (CI). Subgroup analyses were conducted based on various factors, including sample size (<1,000 vs. ≥1,000), follow-up duration (<2 years vs. ≥2 years), study quality (assessed by a score of <7 vs. ≥7), ethnicity (Non-Asian vs. Asian), study design (prospective vs. retrospective), type of heart failure (HF) (acute vs. chronic), presence of hyperuricemia (yes or no), left ventricular ejection fraction (LVEF) thresholds (≥45% vs. ≥50%), and the type of uric acid-lowering therapy (traditional vs. novel).
RESULTS
The analysis included a total of 12 studies. Elevated serum uric acid levels were significantly linked to an increased risk of all-cause mortality [relative risk (RR): 1.21, 95% CI: 1.06-1.37, = 0.004] and cardiovascular (CV) mortality (RR: 1.71, 95% CI: 1.42-2.04, < 0.001) in HFpEF patients. Subgroup analyses confirmed this association, particularly in non-Asian populations, those with chronic HFpEF, and studies with a follow-up duration of two years or more. Additionally, higher uric acid levels were associated with an increased risk of HF-related hospitalization [hazard ratio (HR): 1.61, 95% CI: 1.12-2.34, = 0.011]. Regarding treatment, uric acid-lowering therapy did not show a significant effect on reducing mortality in HFpEF patients. However, it was associated with a decreased risk of hospitalization due to HF (RR: 0.85, 95% CI: 0.79-0.91, < 0.001).
CONCLUSION
The findings of this study highlight the prognostic significance of serum uric acid levels in HFpEF and suggest that uric acid-lowering therapy may be beneficial in reducing the incidence of HF hospitalizations. Further research is warranted to elucidate the mechanisms by which uric acid-lowering therapy confers its potential benefits.
PubMed: 38938653
DOI: 10.3389/fcvm.2024.1403242 -
JACC. Advances Oct 2023The use of mobile health (mHealth, wireless communication devices, and/or software technologies) in health care delivery has increased rapidly in recent years. Their...
BACKGROUND
The use of mobile health (mHealth, wireless communication devices, and/or software technologies) in health care delivery has increased rapidly in recent years. Their integration into disease management programs (DMPs) has tremendous potential to improve outcomes for patients with coronary artery disease (CAD), yet a more robust evaluation of the evidence is required.
OBJECTIVES
The purpose of this study was to undertake a systematic review and meta-analysis of mHealth-enabled DMPs to determine their effectiveness in reducing readmissions and mortality in patients with CAD.
METHODS
We systematically searched English language studies from January 1, 2007, to August 3, 2021, in multiple databases. Studies comparing mHealth-enabled DMPs with standard DMPs without mHealth were included if they had a minimum 30-day follow-up for at least one of all-cause or cardiovascular-related mortality, readmissions, or major adverse cardiovascular events.
RESULTS
Of the 3,411 references from our search, 155 full-text studies were assessed for eligibility, and data were extracted from 18 publications. Pooled findings for all-cause readmissions (10 studies, n = 1,514) and cardiac-related readmissions (9 studies, n = 1,009) indicated that mHealth-enabled DMPs reduced all-cause (RR: 0.68; 95% CI: 0.50-0.91) and cardiac-related hospitalizations (RR: 0.55; 95% CI: 0.44-0.68) and emergency department visits (RR: 0.37; 95% CI: 0.26-0.54) compared to DMPs without mHealth. There was no significant reduction for mortality outcomes (RR: 1.72; 95% CI: 0.64-4.64) or major adverse cardiovascular events (RR: 0.68; 95% CI: 0.40-1.15).
CONCLUSIONS
DMPs integrated with mHealth should be considered an effective intervention for better outcomes in patients with CAD.
PubMed: 38938339
DOI: 10.1016/j.jacadv.2023.100591 -
Renal Failure Dec 2024To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis.
METHODS
The PubMed, EmBase, and the Cochrane library were systematically searched for eligible studies from inception till May 2024. All of pooled analyses were performed using the random-effects model.
RESULTS
Fifty observational studies involving 17,558 CKD patients were selected. The prevalence of PH in CKD patients was 38% (95% confidence interval [CI]: 33%-43%), and the prevalence according to CKD status were 31% (95% CI: 20%-42%) for CKD (I-V), 39% (95% CI: 25%-54%) for end stage kidney disease (ESKD) (predialysis), 42% (95% CI: 35%-50%) for ESKD (hemodialysis), and 26% (95% CI: 19%-34%) for renal transplant. We noted the risk factors for PH in CKD included Black individuals (relative risk [RR]: 1.39; 95% CI: 1.18-1.63; < 0.001), chronic obstructive pulmonary disease (RR: 1.48; 95% CI: 1.21-1.82; < 0.001), cardiovascular disease history (RR: 1.62; 95% CI: 1.05-2.51; = 0.030), longer dialysis (RR: 1.70; 95% CI: 1.18-2.46; = 0.005), diastolic dysfunction (RR: 1.88; 95% CI: 1.38-2.55; < 0.001), systolic dysfunction (RR: 3.75; 95% CI: 2.88-4.87; < 0.001), and grade 5 CKD (RR: 5.64; 95% CI: 3.18-9.98; < 0.001). Moreover, PH in CKD patients is also associated with poor prognosis, including all-cause mortality, major cardiovascular events, and cardiac death.
CONCLUSION
This study systematically identified risk factors for PH in CKD patients, and PH were associated with poor prognosis. Therefore, patients with high prevalence of PH should be identified for treatment.
Topics: Humans; Hypertension, Pulmonary; Renal Insufficiency, Chronic; Prevalence; Prognosis; Risk Factors; Renal Dialysis; Observational Studies as Topic
PubMed: 38938193
DOI: 10.1080/0886022X.2024.2368082 -
Health Technology Assessment... Jun 2024To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund...
BACKGROUND
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
METHODS
The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
RESULTS
Among isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
CONCLUSION
This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
LIMITATIONS
Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
FUTURE WORK
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
STUDY REGISTRATION
No registration of this study was undertaken.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in ; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Cephalosporins; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; England; Technology Assessment, Biomedical; Cefiderocol; Gram-Negative Bacterial Infections; State Medicine; Quality of Life
PubMed: 38938145
DOI: 10.3310/YGWR4511 -
Thrombosis Journal Jun 2024In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually...
BACKGROUND
In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually used as anticoagulation therapy during ECMO support. However, heparin-induced thrombocytopenia (HIT) in ECMO-supported patients, which results in considerable morbidity and mortality, has not yet been well described. This meta-analysis and systematic review aimed to thoroughly report the incidence of HIT on ECMO, as well as the characteristics and outcomes of HIT patients.
METHODS
We searched the PubMed, Embase, Cochrane Library, and Scopus databases for studies investigating HIT in adult patients supported by ECMO. All studies conforming to the inclusion criteria were screened from 1975 to August 2023. Nineteen studies from a total of 1,625 abstracts were selected. The primary outcomes were the incidence of HIT and suspected HIT.
RESULTS
The pooled incidence of HIT in ECMO-supported patients was 4.2% (95% CI: 2.7-5.6; 18 studies). A total of 15.9% (95% CI: 9.0-22.8; 12 studies) of patients on ECMO were suspected of having HIT. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used immunoassay. The median optical density (OD) of the ELISA in HIT-confirmed patients ranged from 1.08 to 2.10. In most studies, the serotonin release assay (SRA) was performed as a HIT-confirming test. According to the subgroup analysis, the pooled incidence of HIT in ECMO patients was 2.7% in studies whose diagnostic mode was functional assays, which is significantly lower than the incidence in studies in which the patients were diagnosed by immunoassay (14.5%). Argatroban was most commonly used as an alternative anticoagulation agent after the withdrawal of heparin. Among confirmed HIT patients, 45.5% (95% CI: 28.8-62.6) experienced thrombotic events, while 50.1% (95% CI: 24.9-75.4) experienced bleeding events. Overall, 46.6% (95% CI: 30.4-63.1) of patients on ECMO with HIT died.
CONCLUSION
According to our study, the pooled incidence of HIT in ECMO-supported patients is 4.2%, and it contributes to adverse outcomes. Inappropriate diagnostic methods can easily lead to misdiagnosis of HIT. Further research and development of diagnostic algorithms and laboratory assays are warranted.
PubMed: 38937784
DOI: 10.1186/s12959-024-00624-5 -
BMC Geriatrics Jun 2024Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty...
BACKGROUND
Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty assessments are utilized in observational research for the older breast cancer population is uncertain. Therefore, the aim of this review was to determine the frequency of use of frailty assessments in studies investigating survival or mortality, and characterize them, concentrating on literature from the past 5 years (2017-2022).
METHODS
MEDLINE, EMBASE and Cochrane Library were systematically queried to identify observational studies (case-control, cohort, cross-sectional) published from 2017-2022 that focus on older females (≥ 65 years) diagnosed with breast cancer, and which evaluate survival or mortality outcomes. Independent reviewers assessed the studies for eligibility using Covidence software. Extracted data included characteristics of each study as well as information on study design, study population, frailty assessments, and related health status assessments. Risk of bias was evaluated using the appropriate JBI tool. Information was cleaned, classified, and tabulated into review level summaries.
RESULTS
In total, 9823 studies were screened for inclusion. One-hundred and thirty studies were included in the final synthesis. Only 11 (8.5%) of these studies made use of a frailty assessment, of which 4 (3.1%) quantified frailty levels in their study population, at baseline. Characterization of frailty assessments demonstrated that there is a large variation in terms of frailty definitions and resulting patient classification (i.e., fit, pre-frail, frail). In the four studies that quantified frailty, the percentage of individuals classified as pre-frail and frail ranged from 18% to 29% and 0.7% to 21%, respectively. Identified frailty assessments included the Balducci score, the Geriatric 8 tool, the Adapted Searle Deficits Accumulation Frailty index, the Faurot Frailty index, and the Mian Deficits of Accumulation Frailty Index, among others. The Charlson Comorbidity Index was the most used alternative health status assessment, employed in 56.9% of all 130 studies. Surprisingly, 31.5% of all studies did not make use of any health status assessments.
CONCLUSION
Few observational studies examining mortality or survival outcomes in older women with breast cancer incorporate frailty assessments. Additionally, there is significant variation in definitions of frailty and classification of patients. While comorbidity assessments were more frequently included, the pivotal role of frailty for patient-centered decision-making in clinical practice, especially regarding treatment effectiveness and tolerance, necessitates more deliberate attention. Addressing this oversight more explicitly could enhance our ability to interpret observational research in older cancer patients.
Topics: Humans; Female; Breast Neoplasms; Frailty; Aged; Observational Studies as Topic; Geriatric Assessment; Frail Elderly; Aged, 80 and over
PubMed: 38937703
DOI: 10.1186/s12877-024-05152-5