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European Journal of Pharmacology Nov 2023Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.
METHODS
Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.
RESULTS
There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).
CONCLUSIONS
DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.
Topics: Rats; Animals; Dexmedetomidine; Rats, Sprague-Dawley; Adrenergic alpha-2 Receptor Agonists; Reperfusion Injury; Inflammation; Ischemia
PubMed: 37778612
DOI: 10.1016/j.ejphar.2023.176090 -
Frontiers in Endocrinology 2023Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy...
AIMS
Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy over its effectiveness, but its safety. We conducted a systematic review to assess the safety of tirzepatide.
METHODS
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias. The systematic review was conducted Revman5.4.
RESULTS
Nine RCTs with a total of 9818 patients were included. The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], ) and discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], ). It also showed that the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (); Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (), discontinuation () and injection-site reaction (); The rates of vomiting and diarrhea were dose-dependence at the range of 5-15mg.
CONCLUSION
The safety profile of tirzepatide is generally acceptable, similar to GLP-1 RAs. It is necessary to pay attention to its specific adverse events (hypoglycemia and discontinuation) at high doses (10mg or higher). Nausea, vomiting, diarrhea, discontinuation and injection-site reaction were dose-dependence among specific dose ranges.As the heterogeneity in different studies by interventions, the results may be with biases and the further confirmation is needed. Meanwhile, more well-designed trials are needed to control the confounding factors and ensure adequate sample size.
Topics: Humans; Diabetes Mellitus, Type 2; Diarrhea; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Hypoglycemia; Hypoglycemic Agents; Nausea; Vomiting
PubMed: 37051199
DOI: 10.3389/fendo.2023.1121387 -
Cureus Dec 2022Obesity is a major health problem worldwide resulting in numerous health conditions such as heart disease, stroke, type 2 diabetes (T2D), and certain types of cancer... (Review)
Review
Obesity is a major health problem worldwide resulting in numerous health conditions such as heart disease, stroke, type 2 diabetes (T2D), and certain types of cancer which are among the leading causes of premature preventable deaths. Recently, glucagon like peptide-1 receptor agonists (GLP-1 RA) has been identified as the most promising intervention in treating obesity. Our systematic review aims to analyze the efficacy of semaglutide, a GLP-1RA in treating obesity. We searched PubMed, Science Direct, and Google Scholar databases to review and distill full-text articles based on the eligibility criteria and involved 12 papers of clinical trials. The review found that semaglutide is safe and effective in treating obesity, and complications reported were primarily gastrointestinal events. Further exploration with more number of clinical trials involving greater sample size and lengthier time of follow-up is essential to determine its efficacy and safety in a diverse group of individuals who are overweight or obese and the dose required along with the duration of treatment.
PubMed: 36654602
DOI: 10.7759/cureus.32610 -
The Cochrane Database of Systematic... Dec 2022Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis.
BACKGROUND
Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with medium-dose (MD) ICS/long-acting beta2-agonist (LABA) combination therapy.
OBJECTIVES
To assess the effectiveness and safety of dual (ICS/LABA) and triple therapies (ICS/LABA/LAMA) compared with each other and with varying doses of ICS in adolescents and adults with uncontrolled asthma.
SEARCH METHODS
We searched multiple databases for pre-registered randomised controlled trials (RCTs) of at least 12 weeks of study duration from 2008 to 18 February 2022.
SELECTION CRITERIA
We searched studies, including adolescents and adults with uncontrolled asthma who had been treated with, or were eligible for, MD-ICS/LABA, comparing dual and triple therapies. We excluded cluster- and cross-over RCTs.
DATA COLLECTION AND ANALYSIS
We conducted a systematic review and network meta-analysis according to the previously published protocol. We used Cochrane's Screen4ME workflow to assess search results and Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome was steroid-requiring asthma exacerbations and asthma-related hospitalisations (moderate to severe and severe exacerbations).
MAIN RESULTS
We included 17,161 patients with uncontrolled asthma from 17 studies (median duration 26 weeks; mean age 49.1 years; male 40%; white 81%; mean forced expiratory volume in 1 second (MEF 1)1.9 litres and 61% predicted). The quality of included studies was generally good except for some outcomes in a few studies due to high attrition rates. Medium-dose (MD) and high-dose (HD) triple therapies reduce steroid-requiring asthma exacerbations (hazard ratio (HR) 0.84 [95% credible interval (CrI) 0.71 to 0.99] and 0.69 [0.58 to 0.82], respectively) (high-certainty evidence), but not asthma-related hospitalisations, compared to MD-ICS/LABA. High-dose triple therapy likely reduces steroid-requiring asthma exacerbations compared to MD triple therapy (HR 0.83 [95% CrI 0.69 to 0.996], [moderate certainty]). Subgroup analyses suggest the reduction in steroid-requiring exacerbations associated with triple therapies may be only for those with a history of asthma exacerbations in the previous year but not for those without. High-dose triple therapy, but not MD triple, results in a reduction in all-cause adverse events (AEs) and likely reduces dropouts due to AEs compared to MD-ICS/LABA (odds ratio (OR) 0.79 [95% CrI 0.69 to 0.90], [high certainty] and 0.50 [95% CrI 0.30 to 0.84], [moderate certainty], respectively). Triple therapy results in little to no difference in all-cause or asthma-related serious adverse events (SAEs) compared to dual therapy (high certainty). The evidence suggests triple therapy results in little or no clinically important difference in symptoms or quality of life compared to dual therapy considering the minimal clinically important differences (MCIDs) and HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA.
AUTHORS' CONCLUSIONS
Medium-dose and HD triple therapies reduce steroid-requiring asthma exacerbations, but not asthma-related hospitalisations, compared to MD-ICS/LABA especially in those with a history of asthma exacerbations in the previous year. High-dose triple therapy is likely superior to MD triple therapy in reducing steroid-requiring asthma exacerbations. Triple therapy is unlikely to result in clinically meaningful improvement in symptoms or quality of life compared to dual therapy considering the MCIDs. High-dose triple therapy, but not MD triple, results in a reduction in all-cause AEs and likely reduces dropouts due to AEs compared to MD-ICS/LABA. Triple therapy results in little to no difference in all-cause or asthma-related SAEs compared to dual therapy. HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA, although long-term safety of higher rather than MD- ICS remains to be demonstrated given the median duration of included studies was six months. The above findings may assist deciding on a treatment option when asthma is not controlled with MD-ICS/LABA.
Topics: Adult; Male; Adolescent; Humans; Middle Aged; Adrenergic beta-2 Receptor Agonists; Network Meta-Analysis; Drug Therapy, Combination; Adrenal Cortex Hormones; Asthma; Muscarinic Antagonists; Nebulizers and Vaporizers; Administration, Inhalation
PubMed: 36472162
DOI: 10.1002/14651858.CD013799.pub2 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
Journal of Perinatology : Official... Feb 2024Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences.... (Review)
Review
Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Pain; Adrenergic alpha-2 Receptor Agonists; Pain Management; Analgesia
PubMed: 37845426
DOI: 10.1038/s41372-023-01802-5 -
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 -
Diabetes, Obesity & Metabolism Jun 2023To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.
AIM
To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).
MATERIALS AND METHODS
We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes.
CONCLUSIONS
SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 36751968
DOI: 10.1111/dom.15009 -
Expert Reviews in Molecular Medicine Dec 2023In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an... (Meta-Analysis)
Meta-Analysis Review
Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis.
In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.
Topics: Female; Humans; Male; Pregnancy; Birth Rate; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Luteal Phase; Meta-Analysis as Topic; Ovulation Induction; Semen; Sperm Injections, Intracytoplasmic; Systematic Reviews as Topic
PubMed: 38095077
DOI: 10.1017/erm.2023.25 -
Journal of Neurophysiology Aug 2023Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from... (Review)
Review
Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from literature published before August 2022 about the effects of cannabinoids on quantifiable measures of motoneuron output. Four databases (MEDLINE, Embase, PsycINFO, and Web of Science CoreCollection) were queried and 4,237 unique articles were retrieved. Twenty-three studies met the inclusion criteria, and the findings from these studies were grouped according to four emergent themes: rhythmic motoneuron output, afferent feedback integration, membrane excitability, and neuromuscular junction transmission. This synthesis of evidence suggests that CB1 agonists can increase the frequency of cyclical patterns of motoneuron output (i.e., fictive locomotion). Furthermore, a majority of the evidence indicates that activating CB1 receptors at motoneuron synapses promotes excitation of motoneurons by enhancing excitatory synaptic transmission and depressing inhibitory synaptic transmission. The collated study results reveal variable effects of cannabinoids on acetylcholine release at the neuromuscular junction, and the influence of cannabinoids in this area requires more work to ensure precision of findings for CB1 agonist and antagonist impact. Altogether, these reports indicate that the endocannabinoid system is integral within the final common pathway and can impact motor output. This review contributes to understanding the effects of endocannabinoids on synaptic integration at the motoneuron and modulation of motor output.
Topics: Cannabinoids; Motor Neurons; Synapses; Synaptic Transmission; Neuromuscular Junction
PubMed: 37283484
DOI: 10.1152/jn.00460.2022