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Current Research in Pharmacology and... 2023Gestational diabetes (GD) is associated with an increase in maternal and fetal morbidity. The risk factors involved have been clearly identified but no prevention... (Review)
Review
BACKGROUND
Gestational diabetes (GD) is associated with an increase in maternal and fetal morbidity. The risk factors involved have been clearly identified but no prevention strategies have yet provided robust evidence of their efficacy. Myoinositol has insulin sensitization properties and is of potential interest in the treatment of the disorder.
AIM
The aim of this work was to assess the efficacy of myoinositol supplementation during pregnancy to prevent GD in patients with known risk factors.
METHOD
A systematic literature review was performed on studies comparing the effects of myoinositol supplementation and placebo on the occurrence of GD in at-risk pregnant women. The main judgement criterion was diagnosis of GD between 24 and 28 gestational weeks by an oral glucose tolerance test. The secondary judgement criteria were the occurrence of maternal fetal complications and the need to initiate insulin treatment to manage GD.
RESULTS
Nine studies were included in the meta-analysis. The results showed a significantly higher risk of GD in patients on placebo than in those receiving myoinositol (RR = 2.58, CI 95%: 1.68 to 3.97, p < 0.0001) but wide variations between studies (I = 71.94%, p < 0.001). And the risk of prematurity was significantly greater in the children of mothers on placebo (RR: 2.15, IC 95%: 1.32 to 3.20, p = 0.002).
CONCLUSION
Myoinositol supplementation taken from the beginning of pregnancy reduces the incidence of GD and could be of interest at a dose of 4 g/day as a prevention strategy for patients with identified risk factors.
PubMed: 36573918
DOI: 10.1016/j.crphar.2022.100140 -
The Journal of Allergy and Clinical... Apr 2023A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with single/multiple food allergies.
OBJECTIVES
To evaluate the efficacy and safety of OMA or OMA+OIT in patients with immunoglobulin E (IgE)-mediated food allergy.
METHODS
An extensive literature search (inception to December 31, 2020) was performed to identify randomized, controlled, and observational studies that assessed OMA as monotherapy or OMA+OIT in patients with IgE-mediated food allergy. The outcomes were an increase in tolerated dose of foods, successful desensitization, sustained unresponsiveness, immunological biomarkers, severity of allergic reactions to food, quality of life (QoL), and safety. A P less than .05 was considered significant.
RESULTS
In total, 36 studies were included. The OMA monotherapy (vs pre-OMA) significantly increased the tolerated dose of multiple foods; increased the threshold of tolerated dose for milk, egg, wheat, and baked milk; improved QoL; and reduced food-induced allergic reactions (all P < .01). The OMA+OIT significantly increased the tolerated dose of multiple foods (vs placebo and pre-OMA), desensitization (vs placebo+OIT and pre-OMA) (all P ≤ .01), and improved QoL (vs pre-OMA) and immunoglobulin G4 levels (both P < .01). No major safety concerns were identified.
CONCLUSIONS
In IgE-mediated food allergy, OMA can help patients consume multiple foods and allow for food dose escalation. As an adjunct to OIT, OMA can also support high-dose desensitization and higher maintenance doses. Further studies are warranted to empirically evaluate the effect of OMA and confirm these findings.
Topics: Humans; Animals; Omalizumab; Quality of Life; Immunoglobulin E; Desensitization, Immunologic; Administration, Oral; Food Hypersensitivity; Allergens; Milk
PubMed: 36529441
DOI: 10.1016/j.jaip.2022.11.036 -
Respiratory Research Dec 2022Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.
METHODS
A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.
RESULTS
Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0-1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.
CONCLUSIONS
LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.
Topics: Humans; Adrenergic beta-2 Receptor Agonists; Exercise Tolerance; Quality of Life; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Exercise; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36522735
DOI: 10.1186/s12931-022-02268-3 -
Clinical Endocrinology Apr 2023Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. As sex steroids impact on anterior pituitary function, there...
OBJECTIVE
Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. As sex steroids impact on anterior pituitary function, there is concern around the efficacy of GHST in peripubertal children, where endogenous sex steroid levels are low. Sex steroid priming before GHST is thought to improve test efficacy in these children, however evidence to support its use in clinical practice is limited. In this systematic review, we addressed the following research questions: Does priming increase GH stimulation test efficacy in peripubertal children? Does priming identify those who would benefit most from treatment in terms of final height? Is there evidence for an optimal sex-steroid priming regimen?
DESIGN, PATIENTS, MEASUREMENTS
The study was registered with PROSPERO and conducted according to PRISMA guidelines. We searched Medline, Cochrane-Library, Scopus, EMBASE and Web-of-Science and included all studies that included GHST in both primed and unprimed children. A GH cut-off of 7 µg/L was used as a threshold for GHD. Study quality was assessed using the Risk-Of-Bias in Non- Randomized Studies (ROBINS-I) tool or the revised Cochrane risk-of-bias tool for Randomised trials.
RESULTS
Fifteen studies met our inclusion criteria, of which 4/15 (27%) were randomised control trials. The majority (9/15) of the studies indicated that priming increases growth hormone response upon GHST in peripubertal children, increasing test specificity. Two studies investigated final height after treatment based on the results of primed versus unprimed GHST. These results indicate that growth hormone treatment based on results of a primed GHST improve outcomes compared with treatment based on an unprimed test.
CONCLUSION
Sex-steroid priming increases the growth hormone response during GHST, resulting in fewer patients meeting the threshold required for a diagnosis of GHD. Unnecessary GH treatment may be avoided in some patients without a detrimental effect on final height. Numerous sex-steroid priming regimens have been used in clinical practice and the majority appear to be effective, but an optimal regimen has not been determined.
Topics: Humans; Child; Adolescent; Growth Hormone; Human Growth Hormone; Gonadal Steroid Hormones; Dwarfism, Pituitary; Growth Disorders; Body Height; Steroids
PubMed: 36515075
DOI: 10.1111/cen.14862 -
Tropical Medicine & International... Jan 2023To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without... (Meta-Analysis)
Meta-Analysis Review
Direct evidence gap on fixed versus adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta-analysis.
OBJECTIVES
To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy.
METHODS
We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy.
RESULTS
Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (ROR ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The ROR for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses.
CONCLUSIONS
We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future.
REGISTRATION
The study protocol was registered in PROSPERO (CRD42019120905).
Topics: Adult; Humans; Evidence Gaps; Chagas Disease; Trypanosoma cruzi; Cardiomyopathies
PubMed: 36420767
DOI: 10.1111/tmi.13831 -
Microbiology Spectrum Dec 2022Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.
Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.
Topics: Humans; Syphilis; Ceftriaxone; Doxycycline; Minocycline; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Penicillins; Tetracycline; Erythromycin; Hypersensitivity; Observational Studies as Topic
PubMed: 36377935
DOI: 10.1128/spectrum.02977-22 -
PloS One 2022To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease.
METHODS
Randomized controlled clinical trials were identified from PubMed, Scopus, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wanfang and Chongqing VIP databases, from the database inception to 31/12/2021. The outcome measures were walking distance measured by treadmill (maximum and pain-free walking distance), ankle-brachial index and adverse events. The quality of included studies was assessed by the Cochrane bias risk assessment tool. A network meta-analysis was carried out with Stata 16.0 software.
RESULTS
There were 29 RCTs included in the study, covering total 5352 patients. Cilostazol was ranked first for both maximum and pain-free walking distance, followed by beraprost and pentoxifylline. For cilostazol, pentoxifylline and beraprost, maximum walking distance increased by 62.93 95%CI(44.06, 81.79), 32.72 95%CI(13.51, 55.79) and 43.90 95%CI(2.10, 85.71) meters, respectively relative to placebo, and pain-free walking distance increased by 23.92 95%CI(11.24, 36.61), 15.16 95%CI(2.33, 27.99) and 19.78 95%CI(-3.07, 42.62) meters. For cilostazol, pentoxifylline, beraprost and cilostazol combined with beraprost, ankle-brachial index increased by 0.06 95%CI(0.04, 0.07), -0.01 95%CI(-0.08, 0.05), 0.18 95%CI(0.12, 0.23) and 0.23 95%CI(0.18, 0.27), respectively relative to placebo. The pentoxifylline and cilostazol was associated with a lower ratio of adverse events than beraprost and cilostazol combined with beraprost.
CONCLUSION
Cilostazol, pentoxifylline and beraprost were all effective treatments for intermittent claudication; cilostazol with good tolerance was likely to be the most effective in walking distance, while beraprost and cilostazol combined with beraprost were more prominent in the ankle-brachial index.
Topics: Humans; Cilostazol; Intermittent Claudication; Network Meta-Analysis; Pentoxifylline; Vasodilator Agents; Randomized Controlled Trials as Topic
PubMed: 36318524
DOI: 10.1371/journal.pone.0275392 -
Frontiers in Endocrinology 2022Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels... (Meta-Analysis)
Meta-Analysis
AIMS
Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM.
MATERIALS AND METHODS
Randomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUC) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies.
RESULTS
A total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, <0.001; I 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, <0.001; I = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues ( for subgroup difference =0.03).
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202280104.
CONCLUSIONS
DPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.
Topics: Male; Humans; Dipeptidyl-Peptidase IV Inhibitors; Glucagon; Secretagogues; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
PubMed: 36313782
DOI: 10.3389/fendo.2022.994944 -
Frontiers in Endocrinology 2022To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria.
METHODS
Systematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg's and Egger's tests.
RESULTS
This meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias.
CONCLUSIONS
Women with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776).
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Glucose Tolerance Test; Diabetes Mellitus, Type 2; Prediabetic State; Pregnancy in Diabetics; Glucose
PubMed: 36277725
DOI: 10.3389/fendo.2022.1012244 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948