-
The Cochrane Database of Systematic... Jul 2023Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of... (Review)
Review
BACKGROUND
Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications.
OBJECTIVES
To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo).
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life.
MAIN RESULTS
We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty).
AUTHORS' CONCLUSIONS
Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.
Topics: Adult; Child; Humans; Adrenal Cortex Hormones; Biological Products; Chronic Disease; Eosinophilic Esophagitis; Proton Pump Inhibitors; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 37470293
DOI: 10.1002/14651858.CD004065.pub4 -
Frontiers in Pharmacology 2023Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of...
Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of life and survivorship in affected patients. Genetic polymorphisms in the CYP3A family have been investigated but the findings have been inconsistent and contradictory. A systematic review identified 12 pharmacogenetic studies investigating genetic variation in and and TIPN. In our candidate gene study, 288 eligible participants (211 taxane participants receiving docetaxel or paclitaxel, and 77 control participants receiving oxaliplatin) were successfully genotyped for and . Genotyping data was transformed into a combined CYP3A metaboliser phenotype: Poor metabolisers, intermediate metabolisers and extensive metabolisers. Individual genotypes and combined CYP3A metaboliser phenotypes were assessed in relation to neurotoxicity, including by meta-analysis where possible. In the systematic review, no significant association was found between and TIPN in seven studies, with one study reporting a protective association. For , one study has reported an association with TIPN, while four other studies failed to show an association. Evaluation of our patient cohort showed that paclitaxel was found to be more neurotoxic than docetaxel ( < 0.001). Diabetes was also significantly associated with the development of TIPN. The candidate gene analysis showed no significant association between either SNP () and the development of TIPN overall, or severe TIPN. Meta-analysis showed no association between these two variants and TIPN. Transformed into combined CYP3A metaboliser phenotypes, 30 taxane recipients were poor metabolisers, 159 were intermediate metabolisers, and 22 were extensive metabolisers. No significant association was observed between metaboliser status and case-control status. We have shown that the risk of peripheral neuropathy during taxane chemotherapy is greater in patients who have diabetes. CYP3A genotype or phenotype was not identified as a risk factor in either the candidate gene analysis or the systematic review/meta-analysis, although we cannot exclude the possibility of a minor contribution, which would require a larger sample size.
PubMed: 37469869
DOI: 10.3389/fphar.2023.1178421 -
Frontiers in Genetics 2023: Various publications suggested that there is an association between single nucleotide polymorphisms (SNP) and a reduced response to statin therapy, but the results...
: Various publications suggested that there is an association between single nucleotide polymorphisms (SNP) and a reduced response to statin therapy, but the results were inconsistent. This study aimed to collectively review these publications to appraise the effect of statins on cholesterol control in carriers of variant alleles. PUBMED, Cochrane and EMBASE were searched systematically to identify reported studies on the lipid responses to statin treatment between carriers of the variant allele the non-variant allele of SNPs. The change from baseline in lipid responses for all included studies were calculated using weighted mean differences (WMD) (with 95% confidence interval (CI)). A meta-analysis was conducted to pool results using either the random-effects model or the fixed effects model. A total of 6 publications comprising of 1,686 subjects for the assessment of total cholesterol, LDL-C and HDL-C and 1,156 subjects for the assessment of triglycerides were included in the meta-analyses. Subjects who were non-carriers of a SNP (-204 A/C (rs3808607), -278 A/C (rs3808607) and rs8192875) had a greater reduction in total cholesterol (overall WMD -0.17, 95% CI -0.29, -0.06) and LDL-C levels (overall WMD -0.16, 95% CI -0.26, -0.05) as compared with subjects who borne the variant allele of SNPs when administered a statin. The presence of variant allele of SNPs may result in suboptimal control of total cholesterol and LDL-C levels as compared with individuals who do not carry the variant allele, when administered an equivalent dose of statin.
PubMed: 37377593
DOI: 10.3389/fgene.2023.1199549 -
Biomedicine & Pharmacotherapy =... Aug 2023Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is particularly common among patients with diabetes mellitus. This raises many problems, both with the differential diagnosis of diabetic and inflammatory neuropathy, as well as the choice of treatment. Intravenous immunoglobulin (IVIG) is one of the therapeutic options. There is evidence for the effectiveness of IVIG in treating about two-thirds of patients. However, no review has been published to date systematising studies evaluating the response to IVIG treatment in patients with CIDP and coexisting diabetes.
METHODS
The present study is based on the PRISMA statement and is registered at PROSPERO (CRD42022356180). The study included searches of the databases of MEDLINE, ERIC, CINAHL Complete, Academic Search Ultimate and Health Source: Nursing/Academic Edition, finally including seven original papers evaluating a total of 534 patients in the review. The main inclusion criteria were the presence of a group of patients with CIDP and comorbid diabetes in the study.
RESULTS
The systematic review showed a lower efficacy of IVIG treatment among patients with coexisting diabetes compared with idiopathic CIDP (61 % vs 71 %). In addition, the presence of conduction blocks on neurography and shorter disease duration proved to be significant factors improving response to treatment.
CONCLUSIONS
Current scientific data do not allow for strong recommendations on the choice of treatment for CIDP. A randomised, multicentre study evaluating the efficacy of different therapeutic approaches to this disease entity needs to be planned.
Topics: Humans; Immunoglobulins, Intravenous; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Infusions, Intravenous; Administration, Intravenous; Diabetes Mellitus; Multicenter Studies as Topic
PubMed: 37290187
DOI: 10.1016/j.biopha.2023.114974 -
Frontiers in Pharmacology 2023Deferasirox is an iron-chelating agent prescribed to patients with iron overload. Due to the interindividual variability of deferasirox responses reported in various...
Deferasirox is an iron-chelating agent prescribed to patients with iron overload. Due to the interindividual variability of deferasirox responses reported in various populations, this study aims to determine the genetic polymorphisms that influence drug responses. A systematic search was performed from inception to March 2022 on electronic databases. All studies investigating genetic associations of deferasirox in humans were included, and the outcomes of interest included pharmacokinetics, efficacy, and adverse drug reactions. Fixed- and random-effects model meta-analyses using the ratio of means (ROM) were performed. Seven studies involving 367 participants were included in a meta-analysis. The results showed that subjects carrying the A allele (AG/AA) of rs2273697 had a 1.23-fold increase in deferasirox C (ROM = 1.23; 95% confidence interval [CI]:1.06-1.43; = 0.007) and a lower Vd (ROM = 0.48; 95% CI: 0.36-0.63; < 0.00001), compared to those with GG. A significant attenuated area under the curve of deferasirox was observed in the subjects with rs3806596 AG/GG by 1.28-fold (ROM = 0.78; 95% CI: 0.60-0.99; = 0.04). In addition, two SNPs of were also associated with the decreased C: rs2248359 CC (ROM = 0.50; 95% CI: 0.29-0.87; = 0.01) and rs2585428 GG (ROM = 0.47; 95% CI: 0.35-0.63; < 0.00001). Only rs2248359 CC was associated with decreased C (ROM = 0.26; 95% CI: 0.08-0.93; = 0.04), while rs2585428 GG was associated with a shorter half-life (ROM = 0.44; 95% CI: 0.23-0.83; = 0.01). This research summarizes the current evidence supporting the influence of variations in genes involved with drug transporters, drug-metabolizing enzymes, and vitamin D metabolism on deferasirox responses.
PubMed: 37261288
DOI: 10.3389/fphar.2023.1069854 -
BMC Psychiatry May 2023Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from pharmacogenetic testing remains unclear. We aim to evaluates the effect of pharmacogenomic testing guiding on clinical outcomes of major depressive disorder.
METHODS
Pubmed, Embase, and Cochrane Library of Clinical Trials were searched from inception until August 2022. Key terms included pharmacogenomic and antidepressive. Odds ratios (RR) with 95% confidence intervals (95%CIs) were calculated using fixed-effects model for low or moderate heterogeneity or random-effects model for high heterogeneity.
RESULTS
Eleven studies (5347 patients) were included. Compared with usual group, pharmacogenomic testing guided group was associated with an increased response rate at week 8 (OR 1.32, 95%CI 1.15-1.53, 8 studies, 4328 participants) and week 12 (OR 1.36, 95%CI 1.15-1.62, 4 studies, 2814 participants). Similarly, guided group was associated with an increased rate of remission at week 8 (OR 1.58, 95%CI 1.31-1.92, 8 studies, 3971 participants) and week 12 (OR 2.23, 95%CI 1.23-4.04, 5 studies, 2664 participants). However, no significant differences were found between the two groups in response rate at week 4 (OR 1.12, 95%CI 0.89-1.41, 2 studies, 2261 participants) and week 24 (OR 1.16, 95%CI 0.96-1.41, 2 studies, 2252 participants), and remission rate at week 4 (OR 1.26, 95%CI 0.93-1.72, 2 studies, 2261 participants) and week 24 (OR 1.06, 95%CI 0.83-1.34, 2 studies, 2252 participants). Medication congruence in 30 days was significantly reduced in the pharmacogenomic guided group compared with the usual care group (OR 2.07, 95%CI 1.69-2.54, 3 studies, 2862 participants). We found significant differences between subgroups of target population in response and remission rate.
CONCLUSION
Patients with major depressive disorder may benefit from pharmacogenomic testing guided treatment by achieving target response and remission rates more quickly.
Topics: Humans; Depressive Disorder, Major; Pharmacogenetics; Antidepressive Agents; Pharmacogenomic Testing; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 37173736
DOI: 10.1186/s12888-023-04756-2 -
Pharmacogenomics Apr 2023To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred... (Meta-Analysis)
Meta-Analysis Review
To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in , , , , , , and were evaluated relative to weight loss with glucagon-like peptide-1 agonists (13 studies) or naltrexone-bupropion (one study). gene (rs1049353), gene (rs6923761, rs10305420), gene (rs7903146) were associated with weight loss in at least one study involving glucagon-like peptide-1 agonist(s). The meta-analysis did not identify any consistent effect of SNVs. Pharmacogenetic interactions for exenatide, liraglutide, naltrexone-bupropion and weight loss were identified, but the directionality was inconsistent.
Topics: Adult; Humans; Hypoglycemic Agents; Pharmacogenetics; Naltrexone; Bupropion; Peptides; Venoms; Glucagon-Like Peptide 1; Weight Loss; Glucagon-Like Peptide-1 Receptor; Diabetes Mellitus, Type 2; Protein Serine-Threonine Kinases
PubMed: 36999540
DOI: 10.2217/pgs-2022-0192 -
Nutrients Mar 2023The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in... (Review)
Review
The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline [PubMed], Scopus, Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (, ), transport (), and metabolism (), as well as in the vitamin D receptor (), are associated with OS and/or PFS in patients with NSCLC. The SNPs in have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the , , , , and genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.
Topics: Humans; Receptors, Calcitriol; Carcinoma, Non-Small-Cell Lung; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Vitamin D3 24-Hydroxylase; Lung Neoplasms; Vitamin D; Polymorphism, Single Nucleotide; Biomarkers; Vitamins; Genetic Predisposition to Disease; Genotype; Case-Control Studies; Cytochrome P450 Family 2
PubMed: 36986255
DOI: 10.3390/nu15061525 -
Journal of Personalized Medicine Mar 2023The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the... (Review)
Review
The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010-2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of , and 3 of . We observed weak unadjusted nominal significant ( < 0.05) additive effects of PGx variants of , , , , , , and (10 variants) on antipsychotic response; , , , , , , , , , and (14 variants) on weight gain; (one variant) on metabolic syndrome; (one variant) on prolactin levels; and (two variants) on TD; HLA-DRB1 (one variant) on CLA; (four phenotypes) and (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.
PubMed: 36983653
DOI: 10.3390/jpm13030471 -
Single-Nucleotide Polymorphisms as Biomarkers of Antipsychotic-Induced Akathisia: Systematic Review.Genes Feb 2023Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to... (Review)
Review
Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to move, resulting in repetitive movements of the limbs and torso, while taking antipsychotics (APs). In recent years, there have been some associative genetic studies of the predisposition to the development of AIA. : The goal of our study was to review the results of associative genetic and genome-wide studies and to systematize and update the knowledge on the genetic predictors of AIA in patients with schizophrenia (Sch). We searched full-text publications in PubMed, Web of Science, Springer, Google Scholar, and e-Library databases from 1977 to 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) quality scale was used for the critical selection of the studies. We identified 37 articles, of which 3 were included in the review. Thus, the C allele of rs1800498 (59414 C>T) and the A allele of rs1800497 (17316 G>A) (TaqIA) from the gene as well as the TT genotype rs13212041 (77461407 C>T) from the gene were found to be associated with AIA. : Uncovering the genetic biomarkers of AIA may provide a key to developing a strategy for the personalized prevention and treatment of this adverse neurological drug reaction of APs in patients with Sch in real clinical practice.
Topics: Humans; Antipsychotic Agents; Psychomotor Agitation; Polymorphism, Single Nucleotide; Schizophrenia; Biomarkers
PubMed: 36980888
DOI: 10.3390/genes14030616