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The Cochrane Database of Systematic... May 2024Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload.
OBJECTIVES
To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults.
SEARCH METHODS
We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence.
MAIN RESULTS
The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics.
AUTHORS' CONCLUSIONS
Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.
Topics: Humans; Heart Failure; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Acute Disease; Infusions, Intravenous; Injections, Intravenous; Bias; Cause of Death; Length of Stay; Adult; Aged
PubMed: 38775253
DOI: 10.1002/14651858.CD014811.pub2 -
Clinical and Applied... 2024Current guidelines recommend the standard-of-care anticoagulation (vitamin K antagonists or low-molecular-weight heparin) in patients with cerebral venous thrombosis... (Meta-Analysis)
Meta-Analysis Review
Current guidelines recommend the standard-of-care anticoagulation (vitamin K antagonists or low-molecular-weight heparin) in patients with cerebral venous thrombosis (CVT). Herein, we performed a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy and safety of direct oral anticoagulants (DOACs) compared with the current standard of care in patients with CVT. We systematically searched the PubMed and Embase databases up to December 2023 to identify clinical trials on the effect of DOACs in patients with CVT. A Mantel-Haenszel fixed effects model was applied, and the effect measures were expressed as the absolute risk differences (RDs) and 95% confidence intervals (CIs). A total of 4 RCTs involving 270 participants were included. In the pooled analysis, DOACs and standard of care had low incidence rates of recurrent VTE and all-cause death, and similar rates of any recanalization (78.2% vs 83.2%; RD = -4%, 95%CI:-14% to 5%) and complete recanalization (60.9% vs 69.4%; RD = -7%, 95%CI:-24% to 10%). Compared with the standard of care, DOACs had non-significant reductions in the rates of major bleeding (1.2% vs 2.4%; RD = -1%, 95%CI: -6% to 3%), intracranial hemorrhage (1.9% vs 3.6%; RD = -2%, 95%CI:-7% to 3%), clinically relevant non-major bleeding (3.8% vs 7.4%; RD = -4%, 95%CI:-9% to 2%), and any bleeding (17.3% vs 21.4%; RD = -4%, 95%CI:-16% to 8%) in patients with CVT. DOACs and standard of care showed similar efficacy and safety profiles for the treatment of CVT. DOACs might be safe and a convenient alternative to vitamin K antagonists for thromboprophylaxis in patients with CVT.
Topics: Humans; Randomized Controlled Trials as Topic; Anticoagulants; Administration, Oral; Venous Thrombosis; Intracranial Thrombosis
PubMed: 38772568
DOI: 10.1177/10760296241256360 -
Archives of Toxicology May 2024Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use.... (Review)
Review
Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.
PubMed: 38769171
DOI: 10.1007/s00204-024-03782-7 -
BMJ Paediatrics Open May 2024At present, limited literature exists exploring patient preferences for prophylactic treatment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Given...
BACKGROUND
At present, limited literature exists exploring patient preferences for prophylactic treatment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Given low treatment completion rates to this treatment in Australia, where the burden of disease predominantly affects Aboriginal and Torres Strait Islander people, an improved understanding of factors driving patient preference is required to improve outcomes. Due to limited available literature, this review sought to explore treatment preferences for conditions for which the findings might be generalisable to the ARF/RHD context.
OBJECTIVE
Explore treatment preferences of patients, parents/caregivers and healthcare providers towards regular injection regimens in paediatric and adolescent populations for any chronic condition. Findings will be applied to the development of benzathine penicillin G (BPG) prophylactic regimens that are informed by treatment preferences of patients and their caregivers. This in turn should contribute to optimisation of successful BPG delivery.
METHODS
A systematic review of databases (Medline, Embase and Global Health) was conducted using a search strategy developed with expert librarian input. Studies were selected using a two-stage process: (1) title and abstract screen and (2) full text review. Data were extracted using a reviewer-developed template and appraised using the JBI Critical Appraisal tool. Data were synthesised according to a thematic analytical framework.
RESULTS
1725 papers were identified by the database search, conducted between 12 February 2022 and 8 April 2022, and 25 were included in the review. Line-by-line coding to search for concepts generated 20 descriptive themes. From these, five overarching analytical themes were derived inductively: (1) ease of use, (2) tolerability of injection, (3) impact on daily life, (4) patient/caregiver agency and (5) home/healthcare interface.
CONCLUSIONS
The findings of this review may be used to inform the development of preference-led regular injection regimens for paediatric and adolescent patient cohorts-specifically for BPG administration in ARF/RHD secondary prophylaxis.
TRIAL REGISTRATION NUMBER
Patient, parent and health personnel preferences towards regular injection regimes in paediatric and adolescent populations-a protocol for a systematic review. PROSPERO 2021 CRD42021284375. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284375.
Topics: Humans; Adolescent; Child; Patient Preference; Rheumatic Fever; Penicillin G Benzathine; Anti-Bacterial Agents; Australia; Injections; Caregivers
PubMed: 38769047
DOI: 10.1136/bmjpo-2023-002450 -
European Journal of Hospital Pharmacy :... May 2024Acute respiratory distress syndrome (ARDS) is a life-threatening, diffuse inflammatory pulmonary condition characterised by the Berlin criteria. Incidence of ARDS is...
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is a life-threatening, diffuse inflammatory pulmonary condition characterised by the Berlin criteria. Incidence of ARDS is estimated at 2.5-19% globally with high mortality and morbidity. Interest has been increasing in the use of inhaled sedatives because of a more rapid awakening and fewer adverse effects compared with intravenous propofol. The primary aim of this systematic review protocol is to investigate the length of critical care stay between ARDS patients who have been mechanically ventilated with inhaled anaesthetic sedatives (ie, sevoflurane and isoflurane) compared with those patients who are prescribed conventional sedatives (ie, propofol).
METHODS AND ANALYSIS
Cochrane Central Register of Controlled Trials, Ovid (Embase, MEDLINE), PubMed, EBSCO (CINAHL Plus), Google Scholar will be searched and stratified by the reviewers. The literature search will be limited to English articles. Published full text peer-reviewed articles will be included.The International Prospective Register of Systematic Reviews (PROSPERO) Registration number is: CRD42023390988.
ETHICS AND DISSEMINATION
Ethics approval is not required for this systematic review. The results will be presented at local/regional meetings and dissemination will occur through peer-reviewed publication.
PubMed: 38768999
DOI: 10.1136/ejhpharm-2024-004117 -
Journal of Controlled Release :... Jul 2024In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as... (Review)
Review
In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.
Topics: Humans; Drug Delivery Systems; Administration, Ophthalmic; Gels; Animals; Biological Availability; Eye; Pharmaceutical Preparations; Ophthalmic Solutions
PubMed: 38768662
DOI: 10.1016/j.jconrel.2024.05.031 -
Stem Cell Research & Therapy May 2024Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with... (Meta-Analysis)
Meta-Analysis
The safety profile of mesenchymal stem cell therapy administered through intrathecal injections for treating neurological disorders: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs).
METHODS
Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed.
RESULTS
303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events-CTCAE version 5.0) (RR: 1.61, 95% CI 1.19-2.19, I = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004-2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416-0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate.
CONCLUSIONS
Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Injections, Spinal; Randomized Controlled Trials as Topic; Nervous System Diseases; Mesenchymal Stem Cells
PubMed: 38764070
DOI: 10.1186/s13287-024-03748-7 -
Heart & Lung : the Journal of Critical... 2024Since the introduction of direct oral anticoagulants (DOACs) and their comparison with vitamin K antagonists (VKAs), conflicting results have been reported regarding the... (Meta-Analysis)
Meta-Analysis Review
Evaluation of the safety and efficacy of direct oral anticoagulants compared with vitamin-k antagonists in the treatment of left ventricular thrombosis. A systematic review and meta-analysis.
BACKGROUND
Since the introduction of direct oral anticoagulants (DOACs) and their comparison with vitamin K antagonists (VKAs), conflicting results have been reported regarding the optimal treatment for left ventricular thrombosis (LVT).
OBJECTIVES
In this meta-analysis, we intend to comprehensively evaluate the safety and efficacy of these treatments.
METHODS
All clinical trials and cohorts that compared the efficacy or safety of VKAs with DOACs in the treatment of LVTs were systematically searched until April 15, 2023.
RESULTS
The results of 32 studies with a pooled sample size of 4213 patients were extracted for meta-analysis. DOACs, especially rivaroxaban and apixaban, cause faster resolution, lower mortality, and fewer complications (SSE and bleeding events) than VKAs in the management of LVTs.
CONCLUSION
Compared with VKAs, DOACs result in significantly faster (only rivaroxaban) and safer resolution of left ventricular thrombosis.
Topics: Humans; Vitamin K; Thrombosis; Heart Ventricles; Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Rivaroxaban; Heart Diseases; Pyrazoles; Pyridones
PubMed: 38754272
DOI: 10.1016/j.hrtlng.2024.04.019 -
PloS One 2024Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the... (Meta-Analysis)
Meta-Analysis
Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the effectiveness of different injection therapies in alleviating the symptoms of carpal tunnel syndrome. Various databases were searched for relevant studies from inception until May 10, 2023. Eligible studies were identified using the patient (P), intervention (I), comparison (C), and outcomes (O) model, which involved (P) participants with carpal tunnel syndrome, (I) an intervention based on injection therapy, (C) the use of placebo or another injectant as a control treatment, and (O) the measurement of clinical and electrodiagnostic outcomes of interest. A total of 18 studies were included in the analysis. The network meta-analysis revealed that platelet-rich plasma is effective in the treatment of carpal tunnel syndrome in terms of symptom and pain relief and functional improvement in both the short and long term, whereas steroids are effective only in the short term. Additionally, injections of dextrose solution may offer long-term pain relief as well as short- and long-term symptom alleviation and functional improvement. The study findings suggest that platelet-rich plasma should be used as the first-line treatment for carpal tunnel syndrome, with dextrose and steroids serving as alternative treatment options.
Topics: Carpal Tunnel Syndrome; Humans; Randomized Controlled Trials as Topic; Platelet-Rich Plasma; Treatment Outcome; Network Meta-Analysis; Injections; Glucose
PubMed: 38753671
DOI: 10.1371/journal.pone.0303537 -
Brazilian Oral Research 2024The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket...
The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket healing after tooth extraction in animal models"? To this end, a systematic review of the literature was carried out in PubMed, Scopus, LILACS, Web of Science, as well as in the gray literature up to May 2023. Preclinical studies that evaluated alveolar healing after tooth extraction and the intake of sodium alendronate compared with placebo were included. Two investigators were responsible for screening the articles independently, extracting the data, and assessing their quality through the SYRCLE's RoB tool for randomized trials in animal studies. The study selection process, study characteristics, risk of bias in studies, impact of alendronate on bone healing, and certainty of evidence were described in text and table formats. Methodological differences among the studies were restricted to the synthesis methods. The synthesis of qualitative results followed the Synthesis Without Meta-analysis (SWiM) reporting guideline. From the 19 included studies, five were considered to have low risk, three were of unclear risk, and eleven presented a high risk of bias. The studies were considered heterogeneous regarding alendronate posology, including its dosage and route of administration. Furthermore, a variety of animal species, different age ranges, diverse teeth extracted, and exposure or not to ovariectomy contributed to the lack of parity of the selected studies. Our results indicated that alendronate monotherapy negatively affects the early phase of wound healing after tooth extraction in preclinical studies, suggesting that the bone resorption process after tooth extraction in animals treated with alendronate might impair the bone healing process of the extraction socket. In conclusion, alendronate administration restrains bone resorption, thereby delaying alveolar socket healing . Future studies should be conducted to validate these findings and to better understand the effects of alendronate therapy on oral tissues.
Topics: Alendronate; Tooth Extraction; Animals; Wound Healing; Tooth Socket; Bone Density Conservation Agents
PubMed: 38747825
DOI: 10.1590/1807-3107bor-2024.vol38.0038