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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 -
Children (Basel, Switzerland) Aug 2023The aim of the present systematic review was to evaluate the clinical and radiographic success of partial pulpotomies in deep caries processes or post-eruptive defects... (Review)
Review
The aim of the present systematic review was to evaluate the clinical and radiographic success of partial pulpotomies in deep caries processes or post-eruptive defects in young, vital permanent teeth. Four electronic databases, PubMed, Scopus, Embase, and Google Scholar, were searched, followed by a manual search in the reference lists. Randomized controlled trials evaluating partial pulpotomy with a follow-up period of ≥12 months were included. A meta-analysis using a random effects model was performed. A total of 3127 articles were retrieved, and after duplicate removal, 2642 were screened by title and abstract; 1 additional article was found during the manual search, and 79 were identified. Finally, six papers were included in the review. Regardless of the partial pulpotomy modalities or material used, there were no significant differences between clinical and radiographic success rates (cumulative success rate 91.8-92.3%). Five studies were included in the meta-analysis that did not indicate any statistically significant differences in success rates when mineral trioxide aggregate was compared to other materials (95% confidence interval: 0.239 to 1.016; = 0.055). The present research systematically evaluates the evidence and summarizes the available data on partial pulpotomy in young permanent teeth. Given its high clinical and radiographic success rate, partial pulpotomy should be considered when vital pulpal therapy needs to be performed in highly damaged young permanent teeth, as this procedure provides a biological benefit and allows more invasive endodontic treatments to be postponed.
PubMed: 37761408
DOI: 10.3390/children10091447 -
Journal of the National Cancer Institute Sep 2023Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI).
METHODS
A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs).
RESULTS
Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI.
CONCLUSIONS
Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies.
Topics: Humans; Female; Breast; Breast Neoplasms; Mastectomy, Segmental; Radiotherapy, Adjuvant
PubMed: 37289549
DOI: 10.1093/jnci/djad100 -
Cancer Cell International Sep 2023In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the... (Review)
Review
BACKGROUND
In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.
METHODS
PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).
RESULTS
Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.
CONCLUSIONS
In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.
PubMed: 37670301
DOI: 10.1186/s12935-023-03045-y -
Sports Medicine and Arthroscopy Review Sep 2023Conservative management has emerged as an attractive option for partial thickness rotator cuff tears (PT-RCTs). A single algorithmic treatment strategy for patients with...
BACKGROUND
Conservative management has emerged as an attractive option for partial thickness rotator cuff tears (PT-RCTs). A single algorithmic treatment strategy for patients with symptomatic PT-RCT has not yet been developed. This systematic review aims to ascertain whether a conservative approach to PT-RCTs yields positive results in terms of clinical outcomes and functional recovery.
METHODS
This is a systematic review of the literature on patients with PT-RCTs receiving conservative treatment with physiotherapy, platelet-rich plasma (PRP) injections, collagen injections, hyaluronic acid (HA) injections, or corticosteroids injections coupled with polydeoxyribonucleotide (PDRN). Outcomes such as the Visual Analog Scale (VAS) for pain, American Shoulder and Elbow Surgeons and Constant-Murley Score evaluations, as well as the Shoulder Pain and Disability Index and Euro Quality of Life-5D questionnaires were reported following a conservative approach.
RESULTS
Eleven studies were included. Six articles explored the outcomes of patients with PT-RCT treated with PRP injections. Significant improvements in VAS for pain were observed. Two studies examined collagen injections and reported variations in VAS for pain and Constant-Murley Score. Sodium hyaluronate and HA injections were studied in two other articles, showing notable improvements in American Shoulder and Elbow Surgeons scores. Corticosteroid and PDRN injections also displayed favorable outcomes. In addition, physical therapy protocols demonstrated improvements in VAS for pain and strength, particularly with eccentric rehabilitation.
CONCLUSIONS
Conservative management of PT-RCTs, involving physical therapy, PRP injections, collagen injections, corticosteroid injections, HA injections, and PDRN in jections, demonstrates favorable clinical outcomes. In addition, favorable results are observed in terms of decreased tear width and improved strength recovery, at least during a short-term follow-up. Unfortunately, long-term insight into the structural integrity of conservatively treated rotator cuff tendons following a partial injury has not been thoroughly evaluated yet.
STUDY DESIGN LEVELS OF EVIDENCE
Level IV-systematic review.
Topics: Humans; Rotator Cuff Injuries; Conservative Treatment; Quality of Life; Treatment Outcome; Shoulder Pain; Adrenal Cortex Hormones; Collagen; Arthroscopy
PubMed: 37976129
DOI: 10.1097/JSA.0000000000000372 -
BJU International Oct 2023To perform a systematic review and network meta-analysis (NMA) to determine the advantages and disadvantages of open (OPN), laparoscopic (LPN), and robot-assisted... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic review and network meta-analysis (NMA) to determine the advantages and disadvantages of open (OPN), laparoscopic (LPN), and robot-assisted partial nephrectomy (RAPN) with particular attention to intraoperative, immediate postoperative, as well as longer-term functional and oncological outcomes.
METHODS
A systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-NMA guidelines. Binary data were compared using odds ratios (ORs). Mean differences (MDs) were used for continuous variables. ORs and MDs were extracted from the articles to compare the efficacy of the various surgical approaches. Statistical validity is guaranteed when the 95% credible interval does not include 1.
RESULTS
In total, there were 31 studies included in the NMA with a combined 7869 patients. Of these, 33.7% (2651/7869) underwent OPN, 20.8% (1636/7869) LPN, and 45.5% (3582/7689) RAPN. There was no difference for either LPN or RAPN as compared to OPN in ischaemia time, intraoperative complications, positive surgical margins, operative time or trifecta rate. The estimated blood loss (EBL), postoperative complications and length of stay were all significantly reduced in RAPN when compared with OPN. The outcomes of RAPN and LPN were largely similar except the significantly reduced EBL in RAPN.
CONCLUSION
This systematic review and NMA suggests that RAPN is the preferable operative approach for patients undergoing surgery for lower-staged RCC.
Topics: Humans; Kidney Neoplasms; Robotics; Network Meta-Analysis; Treatment Outcome; Robotic Surgical Procedures; Nephrectomy; Postoperative Complications; Laparoscopy; Retrospective Studies
PubMed: 37259476
DOI: 10.1111/bju.16093 -
Cancer Investigation Sep 2023RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered... (Review)
Review
RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.
Topics: Humans; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Hypertension; Neutropenia; Protein Kinase Inhibitors; Lung Neoplasms; Proto-Oncogene Proteins c-ret
PubMed: 37782113
DOI: 10.1080/07357907.2023.2255655 -
Lasers in Medical Science Jul 2023Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric...
Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric population remain sparse. To determine the efficacy and safety of lasers and IPL for hair reduction in children and adolescents, a systematic review was conducted of original studies evaluating hair removal with lasers or IPL in patients aged less than 18 years. Primary outcome measures were efficacy and safety of treatment. The literature review yielded 2 retrospective cohort studies and 11 case reports/case series including a total of 71 patients aged 9 months to 17 years. Diagnoses ranged from localized lumbosacral to generalized hypertrichosis. Six treatment modalities were evaluated: alexandrite, Nd:YAG, Q-switched Nd:YAG, ruby, and diode lasers and IPL. Only one of the cohort studies (n = 28), using the ruby laser, provided efficacy data. The results showed a 63% hair loss in 89% of patients after completion of treatment, although partial regrowth was evident during 6 to 32 weeks of follow-up. Most of the case reports and case series (10/11) reported significant hair reduction following laser and IPL treatments. None of the patients experienced scarring or dyspigmentation. Some kind of pain management was necessary in 65% of patients; 25% required general anesthesia. On the basis of the limited available data which consisted primary of case reports and case series, lasers and IPL might be effective for pediatric hair reduction. Recurrence following treatment may be higher in children than adults, and pain control may be a limiting factor.
Topics: Adult; Adolescent; Humans; Child; Hair Removal; Retrospective Studies; Phototherapy; Hair; Laser Therapy; Lasers, Solid-State; Treatment Outcome
PubMed: 37402025
DOI: 10.1007/s10103-023-03821-2 -
Communications Medicine Oct 2023Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR,...
BACKGROUND
Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology.
METHODS
Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy.
RESULTS
10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions.
CONCLUSIONS
The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.
PubMed: 37794082
DOI: 10.1038/s43856-023-00368-9 -
Translational Psychiatry Jun 2024Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one... (Review)
Review
Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.
Topics: Humans; Brain; Mental Disorders; Autism Spectrum Disorder; Depressive Disorder, Major; Canonical Correlation Analysis; Attention Deficit Disorder with Hyperactivity; Least-Squares Analysis
PubMed: 38824172
DOI: 10.1038/s41398-024-02954-4