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Pulmonary Pharmacology & Therapeutics Dec 2023Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important... (Meta-Analysis)
Meta-Analysis Review
Safety and efficacy of P2X3 receptor antagonist for the treatment of refractory or unexplained chronic cough: A systematic review and meta-analysis of 11 randomized controlled trials.
BACKGROUND AND OBJECTIVES
Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important part in nerve fiber sensitization and pathological pain pathways. We conducted this systematic review and meta-analysis to determine the long-term safety and efficacy of P2X3 receptor antagonist drugs in chronic cough.
METHODS
We systematically searched PubMed, Scopus, Web of Science, and Embase to identify all relevant published studies through January 15, 2023 that assessed P2X3 antagonists in chronic cough. The protocol was registered in the PROSPERO database with ID: CRD42023422408. Efficacy outcomes were awake (daytime) cough frequency, night cough frequency, 24-h cough frequency, Cough Severity Diary, and total Leicester Cough Questionnaire score. We used the random-effect model to pool the data using RStudio and CMA software.
RESULTS
A total of 11 randomized controlled trials comprising 1350 patients receiving a p2x3 antagonist compared to the placebo group were included in this meta-analysis. A significant decrease in 24-h cough frequency (MD = -4.99, 95% CI [-7.15 to -2.82], P < 0.01), awake (daytime) cough frequency (MD = -7.18, 95% CI [-9.98 to 4.37], P < 0.01), and total Leicester Cough Questionnaire score (MD = 1.74, 95% CI [1.02 to 2.46], P < 0.01) exhibited between the P2X3 antagonist and placebo groups. The frequency of the night cough showed an insignificant difference between the two groups. According to the safety, drug-related adverse events, dysgeusia, hypogeusia, and ageusia significantly increased between the P2X3 antagonist and placebo groups.
CONCLUSION
P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia.
Topics: Humans; Purinergic P2X Receptor Antagonists; Ageusia; Dysgeusia; Chronic Disease; Randomized Controlled Trials as Topic; Cough
PubMed: 37678663
DOI: 10.1016/j.pupt.2023.102252 -
Pain and Therapy Aug 2023Chronic refractory low back and lower extremity pain recalcitrant to conservative management and epidural injections secondary to postsurgery syndrome, spinal stenosis,... (Review)
Review
INTRODUCTION
Chronic refractory low back and lower extremity pain recalcitrant to conservative management and epidural injections secondary to postsurgery syndrome, spinal stenosis, and disc herniation are sometimes managed with percutaneous adhesiolysis. Consequently, this systematic review and meta-analysis was undertaken to assess the efficacy of percutaneous adhesiolysis in managing low back and lower extremity pain.
METHODS
A systematic review and meta-analysis of randomized controlled trials (RCTs) utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases from 1966 to July 2022, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included trials, meta-analysis, and best evidence synthesis was performed. The primary outcome measure was a significant reduction in pain (short term up to 6 months and long term more than 6 months).
RESULTS
The search identified 26 publications, with 9 trials meeting the inclusion criteria. The results of dual-arm and single-arm analyses showed significant improvement in pain and function at 12 months. Opioid consumption was also significantly reduced at 6 months with dual-arm analysis, whereas single-arm analysis showed a significant decrease from baseline to treatment at the 3-, 6-, and 12-month analyses. At 1 year follow-up, seven of seven trials were positive for improvements in pain relief, function, and diminution of opioid use.
DISCUSSION
Based on the present systematic review of nine RCTs, the evidence level is I to II, with moderate to strong recommendation for percutaneous adhesiolysis in managing low back and lower extremity pain. The limitations of the evidence include paucity of literature, lack of placebo-controlled trials, and the majority of the trials studying post lumbar surgery syndrome.
CONCLUSION
The evidence is level I to II or strong to moderate based on five high-quality and two moderate-quality RCTs, with 1 year follow-up that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain.
PubMed: 37227685
DOI: 10.1007/s40122-023-00508-y -
Cureus Oct 2023Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and... (Review)
Review
Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and surgical procedures. This systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration, delves into the latest advancements and implications of robotic systems in SEEG, while meticulously evaluating outcomes and safety measures. Among 855 patients suffering from medication-refractory epilepsy who underwent SEEG in 29 studies, averaging 24.6 years in age, the most prevalent robots employed were robotic surgical assistant (ROSA) (450 patients), Neuromate (207), Sinovation (140), and ISys1 (58). A total of 8,184 electrodes were successfully implanted, with an average operative time of 157.2 minutes per procedure and 15.1 minutes per electrode, resulting in an overall mean operative time of 157.7 minutes across all studies. Notably, the mean target point error (TPE) stood at 2.13 mm, the mean entry point error (EPE) at 1.48 mm, and postoperative complications occurred in 7.69% of robotically assisted (RA) SEEG cases (60), with 85% of these complications being asymptomatic. This comprehensive analysis underscores the safety and efficacy of RA-SEEG in patients with medication-refractory epilepsy, characterized by low complication rates, reduced operative time, and precise electrode placement, supporting its widespread adoption in clinical practice, with no discernible differences noted among the various robotic systems.
PubMed: 38021558
DOI: 10.7759/cureus.47675 -
Cureus Sep 2023The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions... (Review)
Review
Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review.
The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions must be considered. In this review, we report the current progress of clinical studies on various monoclonal antibody therapies and their future potential as primary interventions for refractory cutaneous sarcoidosis. In this systematic review, clinical studies on the management of refractory cutaneous sarcoidosis were retrieved from PubMed and ScienceDirect databases. Studies were screened based on article type, publication within the last 10 years, and access to free full text. The articles selected consisted of case studies, clinical trials, and observational studies. The studies needed to focus on cases of diagnosed cutaneous sarcoidosis at the time of the study and involve adult patients resistant to corticosteroid regimens, with or without additional immunomodulators. Only interventions that included tumor necrosis factor-alpha (TNF-α) (e.g., infliximab and adalimumab) or Janus kinase/signal transducers and activators of transcription (JAK/STAT) (e.g., ruxolitinib and tofacitinib) antibody therapy were considered. Two authors independently conducted quality assessments using the Joanna Briggs Institute Critical Appraisal and NIH Study Quality Assessment tools. A total of 16 clinical studies were included in this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Of the 16 cases included, 15 studies demonstrated partial to complete resolution of cutaneous lesions within a range of two weeks to 18 months from initiation of antibody therapy. Studies on anti-TNF-α intervention demonstrated the most adverse events, including two deaths and one case associated with cutaneous exacerbation. Studies on anti-JAK-STAT interventions demonstrate no adverse events after treatment; however, patient study size was limiting. Recent studies have shown promising potential for anti-TNF-α and anti-JAK-STAT inhibitors to become the mainstay interventions in refractory cutaneous sarcoidosis. Due to limited population studies, the current data on the efficacy and safety of antibody therapies have not yielded a standardized FDA-approved steroid-sparing treatment. Therefore, a need for more population studies on the effectiveness of third-line intervention in refractory cutaneous sarcoidosis is necessary.
PubMed: 37818515
DOI: 10.7759/cureus.44901 -
Annals of Noninvasive Electrocardiology... Sep 2023Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF.
METHODS
A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533.
RESULTS
We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]).
CONCLUSION
Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.
Topics: Humans; Electric Countershock; Ventricular Fibrillation; Out-of-Hospital Cardiac Arrest; Network Meta-Analysis; Electrocardiography; Cardiopulmonary Resuscitation
PubMed: 37482919
DOI: 10.1111/anec.13075 -
Clinical Cardiology Jan 2024Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.
Topics: United States; Humans; Cardiomyopathy, Hypertrophic; Heart; Disease Progression; Heart Failure; Myosins
PubMed: 38269637
DOI: 10.1002/clc.24207 -
Nutrition Reviews Mar 2024Epilepsy is one of the most prevalent neurological disorders in childhood. Antiepileptic drugs are the preferred treatment. However, 30% of children continue suffering... (Meta-Analysis)
Meta-Analysis
CONTEXT
Epilepsy is one of the most prevalent neurological disorders in childhood. Antiepileptic drugs are the preferred treatment. However, 30% of children continue suffering seizures. A ketogenic diet (KD) is one of the emerging alternative treatments.
OBJECTIVE
This review aims to analyze the current evidence regarding the use of a KD for the treatment of refractory epilepsy (RE) in childhood.
DATA SOURCES
A systematic review of reviews was performed, based on MEDLINE (PubMed) as at January 2021.
DATA EXTRACTION
The data extracted included the first author's last name; the year of publication; the country; the study design; the population; the diagnosis, concept, and description of KD types; and major outcome.
RESULTS
Twenty-one reviews were included, 8 with systematic methodology (2 of them included a meta-analysis) and 13 with unsystematic methodology. The main difference between the 2 types of reviews is the reproducibility of their methodology. Therefore, the results of each type of review were analyzed separately. Each type of review described 4 categories of KD: classic KD, modified Atkins diet (MAD), use of medium-chain triglycerides (MCTs), and low glycemic index treatment (LGIT). In terms of effectiveness, the considered systematic reviews reported reductions in the frequency of seizures greater than 50% in about half of the patients. Reviews without systematic methodology reported that 30%-60% of the children showed a 50% or greater reduction in seizures. The most frequently described adverse effects in the 8 systematic reviews were: vomiting (6/8), constipation (6/8), and diarrhea (6/8); and in the unsystematic reviews: vomiting and nausea (10/13), constipation (10/13), and acidosis (9/13).
CONCLUSION
KD can be an effective treatment for RE, with a more than 50% reduction in the frequency of seizures and cognitive improvement being achieved in half of the pediatric patients. The effectiveness of the various types of KD is comparable, and the KD can be adapted to the needs of the patient.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021244142.
Topics: Child; Humans; Adolescent; Diet, Ketogenic; Drug Resistant Epilepsy; Diet, Carbohydrate-Restricted; Reproducibility of Results; Seizures; Treatment Outcome; Constipation; Vomiting
PubMed: 37400987
DOI: 10.1093/nutrit/nuad071 -
Hematology (Amsterdam, Netherlands) Dec 2023Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory multiple myeloma (RRMM), whereas its optimal timing and drug combination remain unclear. In order to assess the various regimens that incorporate selinexor, a systematic review and meta-analysis was conducted.
METHODS
Clinical trials and real-world studies involving MM patients treated with selinexor were included. Pooled risk ratio (RR) was calculated to compare the rates, along with a 95% confidence interval (CI) and concurrent -value assessment. A random-effects model was employed to provide a more conservative evaluation.
RESULTS
A total of 16 studies enrolling 817 patients were reviewed. The usage of selinexor as the fifth-line or prior therapy achieved a higher objective response rate (ORR) (65.9% versus 23.4%, < 0.01) and longer pooled progression-free survival (PFS) (median: 12.5 months versus 2.9 months, < 0.01) than those after the fifth-line usage. In addition, early usage also resulted in a consistent trend of pooled overall survival (median: 22.7 months versus 8.9 months, = 0.26), compared with post-fifth-line usage. Selinexor and dexamethasone (Xd) plus either protease inhibitors (PIs) or immunomodulatory drugs (IMiDs) achieved better ORRs than the Xd-only regimen for RRMM, with ORRs of 56.1%, 52.5% and 24.6%, respectively (< 0.01).
CONCLUSION
In conclusion, using selinexor as the fifth-line or prior therapy had a beneficial impact on RRMM. The regimen of Xd plus PIs or IMiDs was recommended.
Topics: Humans; Multiple Myeloma; Immunomodulating Agents; Dexamethasone; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36920065
DOI: 10.1080/16078454.2023.2187972 -
Leukemia Research Oct 2023Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a...
Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.
Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.
Topics: Humans; Idarubicin; Leukemia, Myeloid, Acute; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37598660
DOI: 10.1016/j.leukres.2023.107368 -
Resuscitation Dec 2023Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence... (Meta-Analysis)
Meta-Analysis Review
Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.
BACKGROUND
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established.
METHODS
We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.
FINDINGS
We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes).
INTERPRETATION
The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
Topics: Adult; Humans; Female; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation; Prognosis; Odds Ratio; Extracorporeal Membrane Oxygenation; Retrospective Studies
PubMed: 37863420
DOI: 10.1016/j.resuscitation.2023.110004