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RMD Open Sep 2023To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large... (Meta-Analysis)
Meta-Analysis
Incidence of infections in patients with psoriatic arthritis and axial spondyloarthritis treated with biological or targeted disease-modifying agents: a systematic review and meta-analysis of randomised controlled trials, open-label studies and observational studies.
OBJECTIVE
To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large group of spondyloarthritis (SpA), treated with tumour necrosis-factor-inhibitors, interleukin-17-inhibitors, Janus kinase-inhibitors, IL-23 or IL-12/23-inhibitors (IL-12/23i), phosphodiesterase 4-inhibitors or cytotoxic T-lymphocyte associated protein 4-Ig.
METHODS
A meta-analysis of randomised controlled trials (RCTs), open-label extension and observational studies was conducted. Serious infections were defined as infections that were life-threatening, required intravenous antibiotics and/or hospitalisation. Non-serious infections did not meet these severity criteria. The incidence rates (IR) were reported for each diagnosis by treatment class and study type using random-effect model to create a 95% CI.
RESULTS
Among 23 333 PsA patients and 11 457 axSpA patients, there were 1.09 serious infections per 100 patient-years (PY) (95% CI 0.85 to 1.35) with similar IR in PsA (0.96 per 100 PY 95% CI 0.69 to 1.28) and axSpA (1.09 per 100 PY 95% CI 0.76 to 1.46). The IR was lower in RCTs (0.77 per 100 PY 95% CI 0.41 to 1.20) compared with observational studies (1.68 per 100 PY 95% CI 1.03 to 2.47). In PsA patients, the lowest IR value was observed with IL-12/23i (0.29 per 100 PY 95% CI 0.00 to 1.03). There were 53.0 non-serious infections per 100 PY (95% CI 43.47 to 63.55) in 7257 PsA patients and 5638 axSpA patients. The IR was higher in RCTs (69.95 per 100 PY 95% CI 61.59 to 78.84) compared with observational studies (15.37 per 100 PY 95% CI 5.11 to 30.97).
CONCLUSION
Serious infections were rare events in RCTs and real-life studies. Non-serious infections were common adverse events, mainly in RCTs.
PROSPERO REGISTRATION NUMBER
CRD42020196711.
Topics: Humans; Arthritis, Psoriatic; Incidence; Interleukin-12; Axial Spondyloarthritis; Research Design; Randomized Controlled Trials as Topic
PubMed: 37714666
DOI: 10.1136/rmdopen-2023-003064 -
Neuropsychology Review Dec 2023Williams syndrome (WS) is a neurodevelopmental disorder caused by a microdeletion in the q11.23 region of chromosome 7. Recent case series reports and clinical case... (Review)
Review
Williams syndrome (WS) is a neurodevelopmental disorder caused by a microdeletion in the q11.23 region of chromosome 7. Recent case series reports and clinical case studies have suggested that the cognitive, behavioral, emotional, and social profile in WS could depend on the genes involved in the deletion. The objective of this systematic review was to analyze and synthesize the variability of the cognitive and behavioral profile of WS with atypical deletion and its probable relationship with the affected genes. The medical subject headings searched were "Williams syndrome," "genotype," "phenotype," "cognitive profile," and "atypical deletion." The studies included were in English or Spanish, with children and adults, and published between January 2000 and October 2022. Twenty-three studies are reported. The characteristics of the participants, the genes involved, the neuropsychological domains and instruments, and the prevalence of the WS cognitive profile criteria were used for the genotype-phenotype analysis. The genes with a major impact on the cognitive profile of WS were (a) LIMK1 and those belonging to the GTF2I family, the former with a greater influence on visuospatial abilities; (b) GTF2IRD1 and GTF2I, which have an impact on intellectual capacity as well as on visuospatial and social skills; (c) FZD9, BAZ1B, STX1A, and CLIP2, which influence the cognitive profile if other genes are also effected; and (d) GTF2IRD2, which is related to the severity of the effect on visuospatial and social skills, producing a behavioral phenotype like that of the autism spectrum. The review revealed four neuropsychological phenotypes, depending on the genes involved, and established the need for more comprehensive study of the neuropsychological profile of these patients. Based on the results found, we propose a model for the investigation of and clinical approach to the WS neuropsychological phenotype.
Topics: Child; Adult; Humans; Williams Syndrome; Genotype; Phenotype; Neurodevelopmental Disorders; Transcription Factors, TFIII; Lim Kinases; Bromodomain Containing Proteins; Transcription Factors
PubMed: 36520254
DOI: 10.1007/s11065-022-09571-2 -
International Journal of Molecular... Jul 2023The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal... (Meta-Analysis)
Meta-Analysis
Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression ( < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; ErbB Receptors; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 37569265
DOI: 10.3390/ijms241511888 -
Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
PharmacoEconomics Aug 2023The anaplastic lymphoma kinase (ALK) inhibitor treatment landscape is rapidly evolving, providing patients with ALK-positive (+) non-small cell lung cancer (NSCLC) with...
A Systematic Review of the Cost-Effectiveness Analyses of Anaplastic Lymphoma Kinase (ALK) Inhibitors in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC).
BACKGROUND
The anaplastic lymphoma kinase (ALK) inhibitor treatment landscape is rapidly evolving, providing patients with ALK-positive (+) non-small cell lung cancer (NSCLC) with multiple therapy options, multiple lines of treatments, and prolonged survival. However, these recent treatment advances have resulted in additional increases in treatment costs. The objective of this article is to review the economic evidence of ALK inhibitors in patients with ALK+ NSCLC.
METHODS
The systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) systematic reviews of economic evaluation. The population included adult patients with locally advanced (stage IIIb/c) or metastatic (stage IV) NSCLC cancer with confirmed ALK fusions. The interventions included the ALK inhibitors alectinib, brigatinib, ceritinib, crizotinib, ensartinib, or lorlatinib. The comparators included the listed ALK inhibitors, chemotherapy, or best supportive care. The review considered cost-effectiveness analysis studies (CEAs) that reported incremental cost-effectiveness ratio in quality-adjusted life years and/or in life years gained. Published literature was searched in Medline (via Ovid) by 4 January 2023, in Embase (via Ovid) by 4 January 2023, in International Pharmaceutical Abstracts (via Ovid) by 4 January 2023, and in Cochrane library (via Wiley) by 11 January 2023. Preliminary screening of titles and abstracts was conducted against the inclusion criteria by two independent researchers followed by a full text of selected citations. Search results are presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Critical appraisal was conducted using the validated Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) tool as well as the Phillips et al. 2004 appraisal tool to assess the reporting and quality of the economic evaluations. Data were extracted from the final set of articles and presented in a table of characteristics of included studies, an overview of study methods of included studies, and a summarization of outcomes of included studies.
RESULTS
A total of 19 studies met all inclusion criteria. The majority of the studies were in the first-line treatment setting (n = 15). Included CEAs varied in the interventions and comparators being evaluated and were conducted from different country perspectives, limiting their comparability. Outcomes from the included CEAs showed that ALK inhibitors may be considered a cost-effective treatment option for patients with ALK+ NSCLC in the first-line and subsequent lines of treatment setting. However, the probability of cost effectiveness of ALK inhibitors ranged from 46 to 100% and were mostly achieved at willingness-to-pay thresholds of $100,000 USD or higher (> $30,000 or higher in China) in the first-line treatment setting and at thresholds of $50,000 USD or higher in subsequent lines of treatment setting. The number of published full-text CEAs is low and the studies represent a handful of country perspectives. The source of survival data was dependent on data from randomized controlled trials (RCTs). Where RCT data were not available, indirect treatment comparisons or matched adjusted indirect comparisons were performed using efficacy data from different clinical studies. Real world evidence was rarely used for efficacy and costing data inputs.
CONCLUSION
The findings summarized available evidence on cost effectiveness of ALK inhibitors for the treatment of patients with locally advanced or metastatic ALK+ NSCLC across lines of treatment settings and generated a valuable overview of analytical approaches utilized to support future economic analyses. To help further inform treatment and policy decisions, this review emphasizes the need for comparative cost effectiveness of multiple ALK inhibitors simultaneously using real-world data sources with broad representation of settings.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Anaplastic Lymphoma Kinase; Crizotinib; Protein Kinase Inhibitors; Lung Neoplasms
PubMed: 37268866
DOI: 10.1007/s40273-023-01279-2 -
Human Psychopharmacology Apr 2024Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential... (Review)
Review
BACKGROUND
Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings.
METHODS
A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials.
RESULTS
The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment.
CONCLUSION
There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.
PubMed: 38683854
DOI: 10.1002/hup.2899 -
Critical Reviews in Oncology/hematology Jun 2024This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy... (Review)
Review
PURPOSE
This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment.
METHODS
A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature.
RESULTS
VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection.
CONCLUSION
While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
Topics: Humans; Glioblastoma; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Brain Neoplasms; Antineoplastic Agents
PubMed: 38677355
DOI: 10.1016/j.critrevonc.2024.104365 -
European Journal of Clinical Nutrition Aug 2023It is unknown whether dietary protein consumption can attenuate resistance exercise-induced muscle damage (EIMD). Managing EIMD may accelerate muscle recovery and allow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is unknown whether dietary protein consumption can attenuate resistance exercise-induced muscle damage (EIMD). Managing EIMD may accelerate muscle recovery and allow frequent, high-quality exercise to promote muscle adaptations. This systematic review and meta-analysis examined the impact of peri-exercise protein supplementation on resistance EIMD.
METHODS
A literature search was conducted on PubMed, SPORTDiscus, and Web of Science up to March 2021 for relevant articles. PEDro criteria were used to assess bias within included studies. A Hedges' g effect size (ES) was calculated for indirect markers of EIMD at h post-exercise. Weighted ESs were included in a random effects model to determine overall ESs over time.
RESULTS
Twenty-nine studies were included in the systematic review and 40 trials were included in ≥1 meta-analyses (16 total). There were significant overall effects of protein for preserving isometric maximal voluntary contraction (MVC) at 96 h (0.563 [0.232, 0.894]) and isokinetic MVC at 24 h (0.639 [0.116, 1.162]), 48 h (0.447 [0.104, 0.790]), and 72 h (0.569 [0.136, 1.002]). Overall ESs were large in favour of protein for attenuating creatine kinase concentration at 48 h (0.836 [-0.001, 1.673]) and 72 h (1.335 [0.294, 2.376]). Protein supplementation had no effect on muscle soreness compared with the control.
CONCLUSION
Peri-exercise protein consumption could help maintain maximal strength and lower creatine kinase concentration following resistance exercise but not reduce muscle soreness. Conflicting data may be due to methodological divergencies between studies. Standardised methods and data reporting for EIMD research are needed.
Topics: Humans; Myalgia; Muscle, Skeletal; Resistance Training; Dietary Proteins; Dietary Supplements; Creatine Kinase
PubMed: 36513777
DOI: 10.1038/s41430-022-01250-y -
Archives of Gerontology and Geriatrics Nov 2023Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to assess the accuracy and bias of six commonly used equations, including the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI) and its combination with cystatin C (CKD-EPI), with the corresponding pair of the Berlin Initiative Study equations (BIS1 and BIS2) and the Full Age Spectrum equations (FAS and FAS).
METHODS
PubMed and the Cochrane Library were searched for studies comparing estimated GFR (eGFR) with measured GFR (mGFR). We analyzed the difference in P30 and bias among the six equations and investigated subgroups based on the area (Asian and non-Asian), mean age (60-74 years and ≥75 years), and levels of mean mGFR (<45 mL/min/1.73m and ≥45 mL/min/1.73m).
RESULTS
27 studies with 18,112 participants were included, all reporting P30 and bias. BIS1 and FAS exhibited significantly higher P30 than CKD-EPI. While no significant differences were observed between FAS and BIS1, or among the three combined equations in terms of either P30 or bias. Subgroup analyses revealed FAS and FAS achieved better results in most situations. However, in the subgroup of mGFR<45 mL/min/1.73m, CKD-EPI had relatively higher P30 and significantly smaller bias.
CONCLUSIONS
Overall, BIS and FAS provided relatively more accurate estimates of GFR than CKD-EPI in older adults. FAS and FAS may be better suited for various conditions, while CKD-EPI would be a better option for older individuals with impaired renal function.
Topics: Aged; Humans; Asian; Creatinine; ErbB Receptors; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Middle Aged; Reproducibility of Results; Models, Biological
PubMed: 37379796
DOI: 10.1016/j.archger.2023.105107 -
The Journal of Experimental Medicine Jun 2024Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered...
Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.
Topics: Humans; Autoimmunity; Colitis; Hypersensitivity; Inflammation; Dermatitis; Janus Kinase 1
PubMed: 38563820
DOI: 10.1084/jem.20232387