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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 -
BMC Cancer Jun 2024Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined.
METHODS
Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies' titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity.
RESULTS
This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research.
CONCLUSION
This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.
Topics: Humans; Volatile Organic Compounds; Lung Neoplasms; Early Detection of Cancer; Breath Tests; Exhalation; Sensitivity and Specificity; Biomarkers, Tumor
PubMed: 38937687
DOI: 10.1186/s12885-024-12537-7 -
Journal of Neurointerventional Surgery Jun 2024Cerebral arteriovenous malformations (AVMs) are complex lesions that can cause hemorrhagic stroke and significant neurological disability. Adenosine induces cardiac...
BACKGROUND
Cerebral arteriovenous malformations (AVMs) are complex lesions that can cause hemorrhagic stroke and significant neurological disability. Adenosine induces cardiac standstill and hypotension, which are thought to be useful during cerebral AVM embolization. Herein, we conducted a systematic review and meta-analysis of the technique's safety.
METHODS
Following PRISMA guidelines, four databases were queried for studies describing the use of adenosine-assisted embolization of cerebral AVMs. Adenosine-related intraoperative complications, permanent neurological outcomes, morbidity, and mortality assessed the technique's safety. Single proportion analysis under a random-effects model was performed. Heterogeneity was assessed using I² statistics, and publication bias was evaluated through funnel plot analysis and Egger's regression test.
RESULTS
Ten studies were included, involving 79 patients (55.7% male) with 79 AVMs (54.4% unruptured and 70.9% Spetzler-Martin grade III-V) who underwent 123 embolizations (80.4% and 5.9% under transarterial and transvenous approaches, respectively) with n-butyl cyanoacrylate (80.4%), ethylene vinyl alcohol (14.4%), or both (5.2%). The incidence of transient adenosine-related intraoperative complications was 0% (95% CI 0% to 3%, I=24%). Besides, the incidence of adenosine-related morbidity, mortality, and permanent outcomes was 0% (95% CI 0% to 3%, I=0%). During follow-up, good functional outcomes were reported for 64 patients (81%).
CONCLUSIONS
Adenosine's effects on blood flow control can facilitate embolization and mitigate the risk of AVM rupture and embolic agent migration. Although current evidence stems from observational studies, the results of this meta-analysis suggest a safe drug profile due to minimal associated morbidity and mortality. Further research from larger randomized and controlled studies is warranted to attain a higher level of evidence.
PROSPERO REGISTRY NUMBER
CRD42023494116.
PubMed: 38937084
DOI: 10.1136/jnis-2024-021866 -
The Lancet. Haematology Jul 2024Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than...
Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than 30 μg/L has a high specificity and sensitivity for diagnosing iron deficiency in adults, but the laboratory reported lower limit of normal (LLN) is typically lower. These LLNs might not be rooted in rigorous scientific evidence and might be contributing to structural underdiagnosis of iron deficiency. A systematic review was done per systematic reviews and meta-analysis guidelines with the use of medical literature databases from inception of each database to Nov 30, 2021, to identify studies that determined ferritin reference intervals in healthy adults and grey literature search for the five most common ferritin assays (registration number CRD42022268844). The objectives were to systematically summarise the ferritin reference intervals and to do a methodological quality assessment of the included studies. 2306 studies were screened and 61 full texts were included. 37 studies were eligible for analysis of the ferritin LLN in the general population. The population the sample was comprised of was a total of 21 882 females and 23 650 males participants. The ferritin LLN was a median of 8 μg/L (IQR 5-15) and mean of 9 μg/L (SD 11) in females and a median of 25 μg/L (IQR 16-44) and mean of 25 μg/L (SD 29) in males. 30 (49%) of 61 studies did not explicitly screen for patients at risk of iron deficiency, and 32 (52%) did not refer to a reference interval establishment guideline (eg, guideline recommended by Clinical and Laboratory Standards Institute). The five most used commercial ferritin laboratory assays reported reference intervals with a median LLN of 11 (IQR 9-12) and mean of 9 μg/L (SD 4) for females and median of 22 (IQR 22-24) and mean of 23 μg/L (SD 4) for males. In the literature, serum ferritin reference intervals in healthy adults consistently report a LLN of less than 30 μg/L. Data driving these ferritin reference intervals are at high risk of bias, given no exclusion of individuals at risk for iron deficiency in the presumed normal population sample and no adherence to reference interval establishment standards. We suggest the use of evidence-based laboratory clinical decision limits to diagnose iron deficiency.
Topics: Adult; Female; Humans; Male; Anemia, Iron-Deficiency; Ferritins; Reference Values
PubMed: 38937026
DOI: 10.1016/S2352-3026(24)00103-0 -
American Journal of Infection Control Jun 2024Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant healthcare-associated infection carrying substantial mortality. We aimed to assess the...
BACKGROUND
Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant healthcare-associated infection carrying substantial mortality. We aimed to assess the clinical impact of active screening cultures for CRAB.
METHODS
A systematic review and meta-analysis, aiming to answer two questions: 1. Does screening vs no screening improve clinical outcomes? 2. Does positive screening ("CRAB carrier") predict CRAB infections? We searched MEDLINE, Cochrane library, Web of Science, and conferences, until January 2024, comparative studies reporting clinical outcomes (mortality, invasive CRAB infections).
RESULTS
Of 5,407 screened publications, 9 studies (10,865 individuals) were included for study question #2. Invasive CRAB infection rate was significantly higher among CRAB carriers (odds ratio [OR] 11.14, 95% confidence interval [CI] 4.95-25.05, with substantial heterogeneity stemming from size rather than direction of the effect). Negative predictive value (NPV) of non-carriage for invasive infection was 97%. CRAB bloodstream infections rate was significantly higher among carriers (OR 16.23, 95% CI 2.9-110.08). No significant difference was demonstrated between the two groups CRAB ventilator-associated pneumonia, length of stay, and mortality. Only one study reported outcomes for the screening vs no screening (study question #1).
CONCLUSIONS
Data to support active CRAB screening are scarce regarding its clinical benefit for patients. Positively screened patients are at significantly higher risk for invasive CRAB infections, with high NPV for non-carriage. This did not translate to reduced mortality.
PubMed: 38936479
DOI: 10.1016/j.ajic.2024.06.017 -
Revista Espanola de Cardiologia... Jun 2024Multivessel percutaneous coronary intervention (MV-PCI) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary...
INTRODUCTION AND OBJECTIVES
Multivessel percutaneous coronary intervention (MV-PCI) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD) without cardiogenic shock. The present network meta-analysis investigated the optimal timing of MV-PCI in this context.
METHODS
We pooled the aggregated data from randomized trials investigating stable STEMI patients with multivessel cad treated with a strategy of either MV-PCI or culprit vessel-only PCI. The primary outcome was all-cause death. The main secondary outcomes were cardiovascular death, myocardial infarction, and unplanned ischemia-driven revascularization. This study is registered at PROSPERO (CRD42023457794).
RESULTS
Among 11 trials, a total of 10 507 patients were randomly assigned to MV-PCI (same sitting, n = 1683; staged during the index hospitalization, n = 3460; staged during a subsequent hospitalization within 45 days, n = 3275) or to culprit vessel-only PCI (n = 2089). The median follow-up was 18.6 months. In comparison with culprit vessel-only PCI, MV-PCI staged during the index hospitalization significantly reduced all-cause death (risk ratio, 0.73; 95%CI, 0.56-0.92; P = .008) and ranked as possibly the best treatment option for this outcome compared with all other strategies. In comparison with culprit vessel-only PCI, a MV-PCI reduced cardiovascular mortality without differences dependent on the timing of revascularization. MV-PCI within the index hospitalization, either in a single procedure or staged, significantly reduced myocardial infarction and unplanned ischemia-driven revascularization, with no significant difference between each other.
CONCLUSIONS
In patients with STEMI and multivessel CAD without cardiogenic shock, multivessel PCI within the index hospitalization, either in a single procedure or staged, represents the safest and most efficacious approach. The different timings of multivessel PCI did not result in any significant differences in all-cause death.
PubMed: 38936467
DOI: 10.1016/j.rec.2024.06.002 -
Medical Mycology Jun 2024Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In...
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.
Topics: Humans; Antifungal Agents; Fusarium; Scedosporium; Microbial Sensitivity Tests; World Health Organization; Mycoses; Fusariosis; Ascomycota; Invasive Fungal Infections
PubMed: 38935914
DOI: 10.1093/mmy/myad128