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Clinical Drug Investigation Apr 2022Atogepant is the latest calcitonin gene-related peptide (CGRP) antagonist approved exclusively for prophylaxis of episodic migraine and is administered orally in doses...
BACKGROUND AND OBJECTIVE
Atogepant is the latest calcitonin gene-related peptide (CGRP) antagonist approved exclusively for prophylaxis of episodic migraine and is administered orally in doses of 10-60 mg/day. This article aims to provide a systematic review of the efficacy and safety of atogepant in migraine prevention.
METHODS
The literature was searched in different databases, i.e., the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2018 to October 2021 using the keywords atogepant, MK-8031, and migraine. Conference abstracts listed in the Cochrane database (includes Embase) and drug information provided by the US Food and Drug Administration (FDA) label were also reviewed. Only English-language clinical trials were included. The authors retrieved 58 articles. Eventually, two randomized, double-blind, multicenter clinical trials involving 1,727 participants and one open-label trial were analyzed.
RESULTS
The FDA approved atogepant for migraine prevention in September 2021 based on two randomized, double-blind, placebo-controlled trials. Atogepant approved for migraine prevention acts as a CGRP receptor antagonist and is administered orally. Based on the 12-week clinical trials, atogepant was efficacious in prevention of migraine and it was well tolerated. The most common treatment-emergent adverse events were nausea, constipation, and upper respiratory infection.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Atogepant had a statistically significant change from baseline in monthly migraine days, monthly headache days, and acute medication use days.
CONCLUSIONS
Atogepant seems to be beneficial for migraine prevention, and it may be of more benefit in individuals who do not wish to take the drug as an injection or do not require a prolonged duration of drug effect. However, head-to-head trials with other CGRP antagonists are required to ascertain its place in migraine prevention.
Topics: Analgesics; Calcitonin Gene-Related Peptide; Double-Blind Method; Headache; Humans; Migraine Disorders; Multicenter Studies as Topic; Piperidines; Pyridines; Pyrroles; Randomized Controlled Trials as Topic; Spiro Compounds; Treatment Outcome
PubMed: 35230651
DOI: 10.1007/s40261-022-01130-0 -
BMJ Open May 2023To evaluate the association between bilirubin levels and stroke risk. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the association between bilirubin levels and stroke risk.
DESIGN
Systematic review and meta-analysis, reported in accordance with Meta-analysis Of Observational Studies in Epidemiology guidelines.
DATA SOURCES
The PubMed, Embase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure Databases were searched from inception up to 27 February 2022.
ELIGIBILITY CRITERIA
Cohort studies assessing the dose-response relationship between bilirubin levels and risk of stroke were eligible for inclusion. There were no language restrictions.
DATA EXTRACTION AND SYNTHESIS
All data from eligible studies were collected and assessed by two independent investigators. We generated pooled relative risks (RRs) with 95% CIs. We used a restricted cubic spline model for the dose-response analyses. Subsequent subgroup analyses were conducted according to stroke outcomes, follow-up duration, geographical area and size of the cohort.
RESULTS
Nine articles including results from 11 cohort studies with 7835 cases of stroke and 263 596 participants met the inclusion criteria. The summarised RR of stroke comparing the highest and lowest bilirubin level was 0.85 (95% CI 0.72 to 0.99). The dose-response analysis indicated that a 15 µmol/L increment of bilirubin level was associated with an 18% lower risk of stroke (RR=0.82, 95% CI 0.67 to 0.99). For ischaemic stroke, the RR was 0.76 (95% CI 0.58 to 0.99). Significant publication bias was not detected.
CONCLUSIONS
Elevated bilirubin levels were associated with a decreased risk of stroke among adults.
PROSPERO REGISTRATION NUMBER
CRD42017071497.
Topics: Adult; Humans; Brain Ischemia; Stroke; Cohort Studies; Ischemic Stroke; Bilirubin
PubMed: 37164466
DOI: 10.1136/bmjopen-2022-064433 -
Birth Defects Research Oct 2022Congenital anomalies affect over 2% of pregnancies, with congenital heart disease (CHD) the most common. Understanding of causal factors is limited. Micronutrients are... (Review)
Review
BACKGROUND
Congenital anomalies affect over 2% of pregnancies, with congenital heart disease (CHD) the most common. Understanding of causal factors is limited. Micronutrients are essential trace elements with key roles in growth and development. We aimed to investigate whether maternal micronutrient deficiencies increase the risk of fetal CHD through systematic review of published literature.
METHOD
We performed a systematic review registered at PROSPERO as CRD42021276699. Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library were searched from their inception until September 7, 2021. Case control trials were included with a population of biological mothers of fetuses with and without CHD. The exposure was maternal micronutrient level measured in pregnancy or the postpartum period. Data extraction was performed by one author and checked by a second. Risk of bias assessment was performed according to the Scottish Intercollegiate Guidelines Network guidance. We performed a narrative synthesis for analysis.
RESULTS
726 articles were identified of which 8 met our inclusion criteria. Final analysis incorporated data from 2,427 pregnancies, 1,199 of which were complicated by fetal CHD assessing 8 maternal micronutrients: vitamin D, vitamin B12, folate, vitamin A, zinc, copper, selenium, and ferritin. Studies were heterogenous with limited sample sizes and differing methods and timing of maternal micronutrient sampling. Definitions of deficiency varied and differed from published literature. Published results were contradictory.
CONCLUSION
There is not enough evidence to confidently conclude if maternal micronutrient deficiencies increase the risk of fetal CHD. Further large-scale prospective study is required to answer this question.
Topics: Copper; Female; Ferritins; Folic Acid; Heart Defects, Congenital; Humans; Malnutrition; Maternal Nutritional Physiological Phenomena; Micronutrients; Observational Studies as Topic; Pregnancy; Selenium; Trace Elements; Vitamin A; Vitamin B 12; Vitamin D; Zinc
PubMed: 35979646
DOI: 10.1002/bdr2.2072 -
Oncotarget Apr 2016Usage of statins is suggested to decrease the incidence of HCC. When it comes to different statin subtypes, the chemopreventive action remains controversial. We aim to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Usage of statins is suggested to decrease the incidence of HCC. When it comes to different statin subtypes, the chemopreventive action remains controversial. We aim to compare the usage of different statins and reduction of HCC risk.
METHODS
We searched PubMed, Embase.com and Cochrane Library database up to August 10, 2015. Duplicated or overlapping reports were eliminated. We performed a traditional pair-wise meta-analysis and a Bayesian network meta-analysis to compare different treatments with a random-effects model.
RESULTS
We reviewed five observational studies enrolling a total of 87127 patients who received at least two different treatment strategies including rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, cerivastatin, and lovastatin or observation alone. Direct comparisons showed that usage of atorvastatin (OR 0.63, 95%CI 0.45-0.89) and fluvastatin (OR 0.58, 95%CI 0.40-0.85) could significantly cut the risk of liver cancer. The difference of indirect comparisons between the included regimens is not statistically significant. However, usage of all types of statins, such as fluvastatin (RR 0.55, 95%CI 0.26-1.11), atorvastatin (RR 0.59, 95%CI 0.30-1.16), simvastatin (RR 0.69, 95%CI 0.38-1.25), cerivastatin (RR 0.71, 95%CI 0.19-2.70), pravastatin (RR 0.72, 95%CI 0.37-1.45), lovastatin (RR 0.81, 95%CI 0.34-1.96) and rosuvastatin (RR 0.92, 95%CI 0.44-1.80), appeared to be superior to observation alone. Notably, fluvastatin was hierarchically the best when compared with the six other statins.
CONCLUSIONS
Our analyses indicate the superiority of usage of statins in reduction of liver cancer. Available evidence supports that fluvastatin is the most effective strategy for reducing HCC risk compared with other statin interventions.
Topics: Atorvastatin; Bayes Theorem; Carcinoma, Hepatocellular; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Liver; Liver Neoplasms; Lovastatin; Observational Studies as Topic; Pravastatin; Pyridines; Rosuvastatin Calcium; Simvastatin; Treatment Outcome
PubMed: 26943041
DOI: 10.18632/oncotarget.7832 -
Drug Safety May 2018Rheumatic diseases are autoimmune, inflammatory diseases often associated with cardiovascular (CV) disease, a major cause of mortality in these patients. In recent... (Review)
Review
INTRODUCTION
Rheumatic diseases are autoimmune, inflammatory diseases often associated with cardiovascular (CV) disease, a major cause of mortality in these patients. In recent years, treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), either as monotherapy or in combination with other drugs, have become the standard of treatment. In this systematic literature review, we evaluated the effect of treatment with biologic or tofacitinib on the CV risk and outcomes in these patients.
METHODS
A systematic search was performed in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for articles reporting on CV risk and events in patients with rheumatic disease treated with a biologic agent or tofacitinib. Articles identified were subjected to two levels of screening. Articles that passed the first level based on title and abstract were assessed on full-text evaluation. The quality of randomized clinical trials was assessed by Jadad scoring system and the quality of the other studies and abstracts was assessed using the Downs and Black instrument. The data extracted included study design, baseline patient characteristics, and measurements of CV risk and events.
RESULTS
Of the 5722 articles identified in the initial search, screening yielded 105 unique publications from 90 unique studies (33 clinical trials, 39 prospective cohort studies, and an additional 18 retrospective studies) that reported CV risk outcomes. A risk of bias analysis for each type of report indicated that they were of good or excellent quality. Importantly, despite some limitations in data reported, there were no indications of significant increase in adverse CV events or risk in response to treatment with the agents evaluated.
CONCLUSIONS
Treatment with biologic or tofacitinib appears to be well-tolerated with respect to CV outcomes in these patients.
Topics: Animals; Antirheumatic Agents; Biological Products; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Piperidines; Prospective Studies; Pyrimidines; Pyrroles; Retrospective Studies; Rheumatic Diseases; Risk Factors
PubMed: 29318514
DOI: 10.1007/s40264-017-0628-9 -
Frontiers in Endocrinology 2021Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current...
Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.
BACKGROUND
Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.
METHODS
A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT's -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT's) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.
CONCLUSION
In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.
SYSTEMATIC REVIEW REGISTRATION
[website], identifier [registration number].
Topics: Female; Folic Acid; Humans; India; Pregnancy; Pregnancy Outcome; Vitamin B 12
PubMed: 33912132
DOI: 10.3389/fendo.2021.619176 -
PloS One 2012Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies.
RESEARCH DESIGN AND METHODS
Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I(2) and Q statistic.
RESULTS
The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15-2.39) for prospective studies, 2.29 (95% CI: 1.48-3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I(2) = 66.3%; Q = 44.16, p<0.001, I(2) = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21-1.43) with heterogeneity (Q = 1.39, p = 0.71, I(2) = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review.
CONCLUSIONS
The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D.
Topics: Animals; Biological Transport; Diabetes Mellitus, Type 2; Heme; Humans; Iron; Risk
PubMed: 22848554
DOI: 10.1371/journal.pone.0041641 -
BMC Pulmonary Medicine Jan 2021Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the...
BACKGROUND
Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality.
METHODS
MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle-Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality-Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE.
RESULTS
Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV/FVC ratio) (4 studies).
CONCLUSION
Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes. PROSPERO registration: CRD42019145747.
Topics: Antioxidants; Bilirubin; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests
PubMed: 33472602
DOI: 10.1186/s12890-021-01395-9 -
PloS One 2022Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been...
INTRODUCTION
Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans.
METHODS
A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection.
RESULTS
1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. All studies were at some risk of bias. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes.
CONCLUSIONS
Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive.
Topics: Communicable Diseases; Genetic Predisposition to Disease; Heme; Heme Oxygenase-1; Humans; Polymorphism, Genetic; Sepsis
PubMed: 35551540
DOI: 10.1371/journal.pone.0267399 -
Clinical Endocrinology Apr 2022Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD).
OBJECTIVE
To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS.
DATA SOURCES
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021.
STUDY SELECTION
The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
DATA EXTRACTION
Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection.
DATA SYNTHESIS
In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I = 75%, very low-grade evidence).
CONCLUSION
There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.
Topics: Atorvastatin; C-Reactive Protein; Cholesterol, LDL; Female; Humans; Metformin; Polycystic Ovary Syndrome
PubMed: 34779013
DOI: 10.1111/cen.14636