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The Cochrane Database of Systematic... Oct 2023This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the... (Review)
Review
BACKGROUND
This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy.
OBJECTIVES
To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults.
SEARCH METHODS
For the latest update, we searched the following databases on 11 November 2021: Cochrane Register of Studies (CRS Web) and Medline (Ovid) 1946 to 10 November 2021. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. We placed no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies.
SELECTION CRITERIA
Randomised placebo-controlled trials of add-on immunomodulatory drug interventions, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. Eligible participants were children (aged over 2 years) and adults with focal epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration. We assessed the following outcomes. 1. 50% or greater reduction in seizure frequency. 2. Seizure freedom. 3. Treatment withdrawal for any reason. 4. Quality of life. 5.
ADVERSE EFFECTS
We used an intention-to-treat (ITT) population for all primary analyses, and we presented results as risk ratios (RRs) with 95% confidence intervals (95% Cl).
MAIN RESULTS
We included three randomised, double-blind, placebo-controlled trials on a total of 172 participants. All trials included children and adults over two years of age with focal epilepsy. Treatment phases lasted six weeks and follow-up from six weeks to six months. One of the three included trials described an adequate method of concealment of randomisation, whilst the other two trials were rated as having an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in all three trials. All analyses were by ITT. One trial was sponsored by the manufacturer of an immunomodulatory agent and therefore was at high risk of funding bias. Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency (risk ratio (RR) 2.30, 95% confidence interval (CI) 1.15 to 4.60; 3 studies, 172 participants; moderate-certainty evidence). For treatment withdrawal, there was insufficient evidence to conclude that people were more likely to discontinue immunomodulatory intervention than placebo (RR 1.04, 95% CI 0.28 to 3.80; 3 studies, 172 participants; low-certainty evidence). The RR for adverse effects was 1.16 (95% CI 0.84 to 1.59; 1 study, 66 participants; low-certainty evidence). Certain adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders were more often associated with immunomodulatory interventions. There were little to no data on cognitive effects and quality of life. No important heterogeneity between studies was found for any of the outcomes. We judged the overall certainty of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals.
AUTHORS' CONCLUSIONS
Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed.
Topics: Adult; Child; Humans; Aged; Anticonvulsants; Quality of Life; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Seizures; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic
PubMed: 37842826
DOI: 10.1002/14651858.CD009945.pub3 -
European Archives of... Feb 2024Specific HPV types cause recurrent respiratory papillomatosis (R.R.P.). When administered intralesionally, cidofovir, an antiviral agent, has shown favorable outcomes in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Specific HPV types cause recurrent respiratory papillomatosis (R.R.P.). When administered intralesionally, cidofovir, an antiviral agent, has shown favorable outcomes in reducing papilloma. Bevacizumab, an angiogenesis inhibitor, has demonstrated improved R.R.P. However, both treatments lack FDA approval for R.R.P. Our study aims to evaluate the efficacy and safety of intralesional Cidofovir and Bevacizumab for R.R.P. and compare the two interventions.
METHODS
We searched five electronic databases to find relevant studies. After the screening, data were extracted from the included studies. Pooled ratios with 95% confidence intervals (CIs) were used for categorical outcomes, and mean difference (MD) was used for continuous outcomes. Statistical heterogeneity was evaluated using the chi-squared test for I statistics. The Cochrane Risk of Bias assessment tool was used to assess the methodological quality of randomized controlled trials (RCTs), while the National Institutes of Health's tool was used for observational studies. Analysis was done by Review Manager software.
RESULTS
In our comprehensive meta-analysis of 35 articles involving 836 patients, cidofovir demonstrated an overall remission ratio of (0.90 [95% CI: 0.83, 0.98], p = 0.01), while bevacizumab (0.92 [95% CI: 0.79, 1.07]), p = 0.3). The complete remission ratio for cidofovir was (0.66 [95% CI: 0.57, 0.75], p > 0.0001), while bevacizumab was (0.29 [95% CI: 0.12, 0.71], p = 0.07). In partial remission, Bevacizumab showed a higher ratio than Cidofovir 0.74 [0.55, 0.99] vs. 0.40 [0.30, 0.54]. Bevacizumab had a pooled ratio of 0.07 [95% CI: 0.02, 0.30] in terms of no remission, indicating better outcomes compared to Cidofovir with a ratio of 0.28 [95% CI: 0.16, 0.51]. Additionally, Cidofovir showed a favorable decrease in the Derkay Severity Score (DSS) with a mean difference (MD) of 1.98 [95% CI: 1.44, 2.52].
CONCLUSION
Cidofovir had a higher impact on complete remission compared to Bevacizumab. Both showed partial remission, with Bevacizumab having a higher ratio. Moreover, Cidofovir showed a significant decrease in DSS. Bevacizumab had lower rates of no remission and recurrence and fewer adverse events compared to Cidofovir. However, the difference between the two treatments was not significant, except for partial remission.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Cidofovir; Injections, Intralesional; Papillomavirus Infections; Respiratory Tract Infections
PubMed: 37831132
DOI: 10.1007/s00405-023-08279-0 -
BMC Nephrology Sep 2023Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021... (Meta-Analysis)
Meta-Analysis
Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021 guideline. However, the efficacy of RTX vs. CYC-based treatments in IMN is still controversial. We performed this systemic review and meta-analysis registered in PROSPERO (CRD 42,022,355,717) by pooling data from randomized controlled trials or cohort studies in IMN patients using the EMBASE, PubMed, and Cochrane libraries (till Orc 1, 2022). The primary outcomes were the complete remission (CR) rate + partial remission (PR) rate. CR rate, immunologic response rate, relapse rate, and the risk of serious adverse events (SAE) were secondary outcomes. Eight studies involving 600 adult patients with IMN were included with a median follow-up duration of 12 to 60 months. RTX induced a similar overall remission rate compared with CYC (RR 0.88, 95% CI: 0.71, 1.09, P = 0.23). At the follow-up time of 6 months, RTX was associated with a lower CR + PR rate compared with CYC (RR 0.67, 95% CI: 0.52, 0.88, P = 0.003). Moreover, RTX might be less effective in inducing CR + PR than CYC treatment in IMN patients with high antiPLA2R antibody levels (RR 0.67, 95% CI: 0.48, 0.94, P = 0.02). The occurrences of CRs, relapse rates, immunologic response rates, and SAE were not significantly different between RTX and CYC, respectively. In conclusion, although the long-term efficacy and safety of CYC compared to RTX were comparable, CYC might respond faster and be more advantageous in IMN patients with high antiPLA2R antibody titers.
Topics: Adult; Humans; Glomerulonephritis, Membranous; Rituximab; Cyclophosphamide; Patients
PubMed: 37740193
DOI: 10.1186/s12882-023-03307-x -
Cureus Jul 2023While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors.... (Review)
Review
While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors. While exclusive enteral nutrition (EEN) is a promising therapy for Crohn's disease (CD), it is not yet considered a first-line treatment. Additionally, the efficacy of EEN compared to corticosteroid treatment is still being investigated. EEN is suggested as a first-line therapy by which guidelines and in which age groups, as it may differ in pediatric and adult recommendations. Another finding was that dietary changes involving an increase in anti-inflammatory foods and decreased intake of foods high in inflammatory compounds are linked to a beneficial outcome both metabolically and microbiologically in patients with ulcerative colitis (UC) in remission. For relevant medical literature, we examined PubMed/Medline, the Cochrane Library, and Google Scholar as examples of medical databases. The articles were identified, evaluated, and eligibility applied, and nine publications were found. The finished articles investigated the role of several diet alternatives for patients with IBD. Some others have shown that following a normal low-fat diet may be effective in reducing the occurrence of subclinical colitis. The EEN and partial enteral nutrition (PEN) indicated no significant differences between both regimens, but both had good outcomes during active IBD. Other strict diets, such as the specific carbohydrate diet (SCD) versus the Mediterranean diet (MD), demonstrate excellent outcomes in patients with IBD. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) dietary counseling improves gastrointestinal symptoms and quality of life in IBD patients. Based on the above, we concluded that more studies determining which component of the diet is not clear (proteins, carbs balanced) or diet types are required to establish a particular diet employed as a treatment intervention in these individuals.
PubMed: 37601990
DOI: 10.7759/cureus.42057 -
Clinical and Experimental Rheumatology Apr 2024To describe the phenotypic, genetic, and outcome characteristics of large-vessel vasculopathy (LVV) in childhood associated with genetic variants. Additionally, a...
OBJECTIVES
To describe the phenotypic, genetic, and outcome characteristics of large-vessel vasculopathy (LVV) in childhood associated with genetic variants. Additionally, a systematic literature review was conducted to delineate the differences between LVV with and without genetic variants.
METHODS
The medical records of all children with LVV seen between January 2000 and September 2022 at our institution were retrospectively reviewed for demographic, clinical and genetic data, and outcomes at the last follow-up visit. In addition, we systematically reviewed the literature for the clinical features and known variants of previously reported cases.
RESULTS
Eleven patients with childhood LVV were identified; five (three males) of them had proven genetic variants (two DOCK8variants, one FOXP3, one DiGeorge syndrome, and one ZNF469 variant), while six patients had sporadic childhood LVV. Remarkably, patients with genetic variants were younger and had early-onset disease. However, the diagnosis of LVV was delayed compared to those without genetic variants. All patients with genetic variants were treated with corticosteroids, and three patients required sequential immunosuppressive drugs. Four patients underwent surgical intervention, and one received a haematopoietic stem-cell transplant (HSCT). Three patients achieved clinical remission, and two died. Furthermore, data from 20 previously published cases was extracted from the literature. All patients had inherited disorders. Of those, 14 patients had a genetically proven diagnosis. Most of them are treated with corticosteroids and immunosuppressive drugs, with partial responses. Two patients underwent HSCT. There were four deaths.
CONCLUSIONS
This study demonstrates that a variety of inherited disorders may contribute to childhood LVV. Strong genetic evidence and the preponderance of autosomal-recessive inheritance may allow us to propose that monogenic LVV is a distinct entity.
Topics: Humans; Phenotype; Male; Child; Female; Child, Preschool; Genetic Predisposition to Disease; Adolescent; Immunosuppressive Agents; Genetic Variation; Retrospective Studies; Infant; Treatment Outcome; Risk Factors; Adrenal Cortex Hormones; Vascular Diseases; Age of Onset; Forkhead Transcription Factors; Hematopoietic Stem Cell Transplantation; Guanine Nucleotide Exchange Factors; DNA-Binding Proteins
PubMed: 37404170
DOI: 10.55563/clinexprheumatol/je8rq2 -
Pituitary Aug 2023Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and partial surgical excision. Despite the cavernous sinus's complexity and risks, new research has improved the surgical procedure and made excision safer. This comprehensive review and single-arm meta-analysis evaluates endocrinological remission and resection rates in pituitary adenomas to determine the benefits and risks of MWCS resection.
METHODS
Databases were systematically searched for studies documenting the resection of the medial wall of the cavernous sinus. The primary outcome was endocrinological remission in patients who underwent resection of the MWCS.
RESULTS
Eight studies were included in the final analysis. The pooled proportion of endocrinological remission (ER) was 63.3%. The excision of MWCS pooled a gross total resection (GTR) proportion of 72.9%. Finally, ICA injury attained a pooled ratio of 0.5%, indicating minimal morbidity in the procedure.
CONCLUSION
The cavernous sinus was ruled out, proving the MWCS excision is safe. Limiting population selection to Knosp 3A or lower enhanced GTR frequencies and lowered recurrence, according to subgroup analyses. This meta-analysis shows that MWCS resection can be a beneficial treatment option for pituitary tumors, when there is no macroscopic medial wall invasion and careful patient selection is done, especially for GH- and ACTH-producing tumors that can cause life-threatening metabolic changes.
Topics: Humans; Pituitary Neoplasms; Cavernous Sinus; Quality of Life; Neoplasm Recurrence, Local; Adenoma; Treatment Outcome; Retrospective Studies
PubMed: 37382779
DOI: 10.1007/s11102-023-01332-5 -
BMC Ophthalmology May 2023To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU).
METHODS
We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated.
RESULTS
Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab.
CONCLUSION
Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.
Topics: Humans; Adalimumab; Infliximab; Antibodies, Monoclonal; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Uveitis; Inflammation
PubMed: 37248486
DOI: 10.1186/s12886-023-02987-1 -
Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.Cureus Mar 2023Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an...
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.
PubMed: 37123777
DOI: 10.7759/cureus.36852 -
Future Oncology (London, England) Feb 2023The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). A systematic literature review of Medline,... (Review)
Review
The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). A systematic literature review of Medline, Embase and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) was performed to identify randomized clinical trials in RRMM reporting median overall survival (mOS), progression-free survival and response end points. The relationship between mOS and response end points was analyzed using Pearson's product-moment correlation. A total of 81 records for 65 original studies, representing 12,827 patients were included. The correlation was moderate for mOS with overall response rate (Pearson r = 0.79), very good partial response (r = 0.73) and duration of response (r = 0.78); all were statistically significant. In linear regression models, estimated mOS gain was 0.48, 0.47 and 1.94 months per percentage point of overall response rate, very good partial response and complete response, respectively (all p < 0.001). Significance was maintained after adjustment for age, relapsed versus refractory multiple myeloma and study year. The analysis was limited by small sample sizes and inconsistent reporting of study-level covariates. These findings support short-term response-based end points as surrogates to survival in RRMM.
Topics: Humans; Multiple Myeloma; Remission Induction; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone
PubMed: 37083162
DOI: 10.2217/fon-2022-0932 -
Journal of Oncology Pharmacy Practice :... Jan 2024Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied....
Immunosuppressive therapy management in cancer patients with autoimmune diseases treated with immune checkpoint inhibitors: A case series and systematic literature review.
INTRODUCTION
Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied. However, guidelines on immunosuppressant (IS) adaptations are limited and real-world evidence is scarce.
METHODS
Current practice of IS adaptations is described in a case series of AID patients treated with ICIs in a tertiary university hospital in Belgium (1/1/2016-31/12/2021). Patient, drug and disease-related data were documented using retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases (1/1/2010-30/11/2022).
RESULTS
Sixteen patients were described in the case series (62% with active AID). Systemic IS were changed before ICI initiation in 5/9 patients. Four patients continued therapy, of which one achieved partial remission. Patients who had IS (partially) stopped before ICI start (n = 4) had AID flares in two cases; immune-related adverse events in three cases. In the systematic review, 37 cases were identified in 9 articles. Corticosteroids (n = 12) and non-selective IS (n = 27) were continued in, respectively, 66% and 68% of patients. Methotrexate was frequently discontinued (13/21). Biologicals, excluding tocilizumab and vedolizumab, were withheld during ICI treatment. Out of all patients with flares (n = 15), 47% had stopped IS therapy before ICI start and 53% had continued their AID drugs.
CONCLUSIONS
A detailed overview of IS management in patients with AID receiving ICI therapy is presented. Expanding the knowledge base germane to IS management with ICI therapy in the diverse population is essential to evaluate their mutual impact, thus advancing responsible patient care.
Topics: Humans; Autoimmune Diseases; Immune Checkpoint Inhibitors; Immunosuppression Therapy; Immunosuppressive Agents; Neoplasms; Retrospective Studies
PubMed: 37051622
DOI: 10.1177/10781552231167824