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The Journal of Obstetrics and... Jul 2023The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine,... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section.
METHODS
The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores.
RESULTS
About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 μg norepinephrine and 81-120 mg phenylephrine; 121-150 μg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 μg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 μg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 μg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores.
CONCLUSIONS
Based on this study, 5-10 mg ephedrine and 13-16 μg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Phenylephrine; Ephedrine; Norepinephrine; Vasoconstrictor Agents; Cesarean Section; Bradycardia; Network Meta-Analysis; Bayes Theorem; Anesthesia, Spinal; Hypotension; Hypertension; Anesthesia, Obstetrical; Double-Blind Method
PubMed: 37170779
DOI: 10.1111/jog.15671 -
Molecular Psychiatry Jun 2023Psychotic disorders are severe mental disorders with poorly understood etiology. Biomarkers in the cerebrospinal fluid (CSF) could provide etiological clues and... (Meta-Analysis)
Meta-Analysis
Psychotic disorders are severe mental disorders with poorly understood etiology. Biomarkers in the cerebrospinal fluid (CSF) could provide etiological clues and diagnostic tools for psychosis; however, an unbiased overview of CSF alterations in individuals with psychotic disorders is lacking. The objective of this study was to summarize all quantifiable findings in CSF from individuals with psychotic disorders compared to healthy controls (HC). Studies published before January 25th, 2023 were identified searching PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO. Screening, full-text review, data extraction, and risk of bias assessments were performed by two independent reviewers following PRISMA guidelines. Findings in patients and healthy controls were compared and summarized using random-effects analyses and assessment of publication bias, subgroup and sensitivity analyses were performed. 145 studies, covering 197 biomarkers, were included, of which 163 biomarkers have not previously been investigated in meta-analyses. All studies showed some degree of bias. 55 biomarkers measured in CSF were associated with psychosis and of these were 15 biomarkers measured in ≥2 studies. Patients showed increased levels of noradrenaline (standardized mean difference/SMD, 0.53; 95% confidence interval/CI, 0.16 to 0.90) and its metabolite 3-methoxy-4-hydroxyphenylglycol (SMD, 0.30; 95% CI: 0.05 to 0.55), the serotonin metabolite 5-hydroxyindoleacetic acid (SMD, 0.11; 95% CI: 0.01 to 0.21), the pro-inflammatory neurotransmitter kynurenic acid (SMD, 1.58; 95% CI: 0.34 to 2.81), its precursor kynurenine (SMD,0.99; 95% CI: 0.60 to 1.38), the cytokines interleukin-6 (SMD, 0.58; 95% CI: 0.39 to 0.77) and interleukin-8 (SMD, 0.43; 95% CI: 0.24 to 0.62), the endocannabinoid anandamide (SMD, 0.78; 95% CI: 0.53 to 1.02), albumin ratio (SMD, 0.40; 95% CI: 0.08 to 0.72), total protein (SMD, 0.29; 95% CI: 0.16 to 0.43), immunoglobulin ratio (SMD, 0.45; 95% CI: 0.06 to 0.85) and glucose (SMD, 0.48; 95% CI: 0.01 to 0.94). Neurotensin (SMD, -0.67; 95% CI: -0.89 to -0.46) and γ-aminobutyric acid (SMD, -0.29; 95% CI: -0.50 to -0.09) were decreased. Most biomarkers showed no significant differences, including the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid. These findings suggest that dysregulation of the immune and adrenergic system as well as blood-brain barrier dysfunction are implicated in the pathophysiology of psychotic disorders.
Topics: Humans; Psychotic Disorders; Biomarkers; Norepinephrine; Dopamine; Homovanillic Acid
PubMed: 37169812
DOI: 10.1038/s41380-023-02059-2 -
The Lancet. Psychiatry Jun 2023Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes.
METHODS
We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109).
FINDINGS
We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use).
INTERPRETATION
Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses.
FUNDING
Australian National Health and Medical Research Council.
Topics: Adult; Humans; Male; Female; Adolescent; Methadone; Buprenorphine; Analgesics, Opioid; Australia; Opioid-Related Disorders; Cocaine
PubMed: 37167985
DOI: 10.1016/S2215-0366(23)00095-0 -
Journal of Cardiovascular Pharmacology Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with...
Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.
Topics: Male; Humans; Female; Young Adult; Adult; Middle Aged; Postural Orthostatic Tachycardia Syndrome; Post-Acute COVID-19 Syndrome; COVID-19; Adrenergic beta-Antagonists; Midodrine; Heart Rate
PubMed: 37094584
DOI: 10.1097/FJC.0000000000001432 -
Annals of Allergy, Asthma & Immunology... Jul 2023Prompt and correct use of epinephrine for treating anaphylaxis is considered essential in reducing the risk of fatal outcomes from anaphylaxis. Nevertheless, prehospital...
BACKGROUND
Prompt and correct use of epinephrine for treating anaphylaxis is considered essential in reducing the risk of fatal outcomes from anaphylaxis. Nevertheless, prehospital use of epinephrine remains low. Although asthma is a common comorbidity in individuals experiencing severe allergic reactions, little attention has been given to whether asthma functions as a predictor of prehospital epinephrine administration.
OBJECTIVE
To perform a scoping review of the extant literature on using epinephrine to manage anaphylaxis in patients with comorbid asthma before presenting to the emergency department.
METHODS
Per Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines, peer-reviewed articles published in English or French were searched for within the Medline, Cumulative Index to Nursing and Allied Health Literature, and Embase databases between June 11 and June 18, 2021. We excluded studies that did not contain primary data.
RESULTS
The literature search yielded 1022 articles that were screened at the title and abstract level by 2 independent reviewers. Of these, 90 (8.8%) advanced to full-text review, and ultimately, 8 studies (0.8% of all articles; 8.9% of full-text articles) were included in the analysis. Overall, the association between comorbid asthma and epinephrine use in the prehospital setting for managing anaphylaxis was inconsistently reported in the literature. Three studies reported a positive association, whereas 2 others suggested a link, but their results were no longer significant when controlling for other study variables. Three studies described no significant association.
CONCLUSION
Although asthma is frequently comorbid in individuals experiencing anaphylaxis, the association between comorbid asthma and prehospital epinephrine treatment rates remains an understudied area of patient care.
Topics: Humans; Anaphylaxis; Asthma; Comorbidity; Emergency Medical Services; Epinephrine
PubMed: 37088194
DOI: 10.1016/j.anai.2023.04.010 -
BMJ Open Apr 2023To demonstrate the therapeutic effect of vasopressin as an alternative treatment for cardiac arrest. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To demonstrate the therapeutic effect of vasopressin as an alternative treatment for cardiac arrest.
DESIGN
Systematic review and meta-analysis.
METHODS
PubMed, EMBASE, the Cochrane Library and Web of Science were searched for randomised controlled trials. The intervention included administration of vasopressin alone or vasopressin combined with epinephrine or vasopressin, steroids and epinephrine (VSE) versus epinephrine combined with placebo as control group. The primary outcome was the return of spontaneous circulation (ROSC). The secondary outcomes included mid-term survival and mid-term good neurological outcome. We conducted subgroup analyses of the primary outcome based on different settings, different study drug strategies and different types of initial rhythm.
RESULTS
Twelve studies (n=6718) were included, of which eight trials (n=5638) reported the data on patients with out-of-hospital cardiac arrest and four trials (n=1080) on patients with in-hospital cardiac arrest (IHCA). There were no significant differences between intravenous vasopressin and placebo in the outcomes of ROSC (relative risk (RR): 1.11; 95% CI: 0.99 to 1.26), mid-term survival (RR: 1.23; 95% CI: 0.90 to 1.66) and mid-term good neurological outcome (RR: 1.20; 95% CI: 0.77 to 1.87). However, in the subgroup analysis, intravenous vasopressin as part of VSE can significantly improve the rate of ROSC (RR: 1.32; 95% CI: 1.18 to 1.47) but not the rate of mid-term survival (RR: 2.15; 95% CI: 0.75 to 6.16) and mid-term good neurological outcome (RR: 1.80; 95% CI: 0.81 to 4.01) for patients with IHCA.
CONCLUSIONS
Our study failed to demonstrate increased benefit from vasopressin with or without epinephrine compared with the standard of care. However, vasopressin as a part of VSE is associated with the improvement of ROSC in patients with IHCA, and the benefit on mid-term survival or mid-term good neurological outcome is uncertain. Larger trials should be conducted in the future to address the effect of vasopressin only, vasopressin plus epinephrine or VSE on cardiac arrest.
PROSPERO REGISTRATION NUMBER
CRD42021293347.
Topics: Humans; Vasoconstrictor Agents; Epinephrine; Vasopressins; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation
PubMed: 37068900
DOI: 10.1136/bmjopen-2022-065061 -
Journal of Intensive Care Medicine Sep 2023The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal... (Meta-Analysis)
Meta-Analysis
The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal tissue perfusion. Capillary refill time (CRT), a marker of skin blood flow, has been validated as a marker of the reperfusion process. The aim of the study was to explore the relationship between MAP and CRT in patients in septic shock. We systematically reviewed studies which reported CRT and MAP in septic shock patients. Authors of eligible studies were asked to provide necessary data for performing a meta-correlation of Spearman's rank correlation coefficients. Subgroup analyses were performed, including studies of good quality and studies with higher/lower norepinephrine doses. We identified 10 studies, comprising 917 patients. There were 5 studies considered to be of good quality. A meta-correlation showed a statistically significant but poor negative correlation between MAP and CRT ( = -0.158, range -0.221 to -0.093, < .001, I2 = 0.0%). Subgroup analysis of best-quality studies gave similar results ( = -0.201, range -0.282 to -0.116, < .001, I2 = 0.0%). In subanalysis concerning norepinephrine doses, no significant correlations were found. In patients with septic shock, there is poor inverse correlation between MAP and CRT. MAP > 65 mm Hg does not guarantee normalization of CRT. PROSPERO: CRD42022355996. Registered on 5 September 2022.
Topics: Humans; Shock, Septic; Arterial Pressure; Hemodynamics; Norepinephrine; Resuscitation
PubMed: 37042043
DOI: 10.1177/08850666231168038 -
The Journal of Allergy and Clinical... Jun 2023Food-dependent exercise-induced allergic reactions can manifest with wheals, angioedema, and anaphylaxis, alone or in combination.
BACKGROUND
Food-dependent exercise-induced allergic reactions can manifest with wheals, angioedema, and anaphylaxis, alone or in combination.
OBJECTIVE
To systematically review the clinical manifestation, culprit foods and exercise, augmenting factors, comorbidities, and treatment options of each phenotype.
METHODS
Using predefined search terms, we assessed and analyzed the relevant literature until June 2021. Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were applied to this systematic review.
RESULTS
A total of 231 studies with 722 patients were included. The most common phenotype was anaphylaxis with wheals, angioedema, or both, reported in 80% of patients. This was associated with a higher number of anaphylactic episodes, augmenting factors, and use of on-demand antihistamine compared with the least common phenotype, anaphylaxis without wheals or angioedema, reported in 4% of patients. Anaphylaxis with wheals/angioedema was also associated with distinct characteristics compared with stand-alone wheals, angioedema, or both, in 17% of patients. Patients with anaphylaxis were older at the time of disease onset, less often had a history of atopy, showed more positive results in response to food and exercise provocation tests, had a more restricted spectrum of culprit foods, and more often used on-demand epinephrine.
CONCLUSIONS
The three phenotypes of allergic reactions to food and exercise differ in clinical characteristics, triggers, and response to treatment. Knowledge of these differences may help with patient education and counseling as well as disease management.
Topics: Humans; Anaphylaxis; Urticaria; Angioedema; Epinephrine; Food Hypersensitivity; Allergens; Phenotype
PubMed: 36997120
DOI: 10.1016/j.jaip.2023.03.035 -
European Journal of Pharmacology Jul 2023The mechanism behind the reinstament of psychostimulant, as a major obstacle in addiction treatment is not fully understood. Controversial data are available in the... (Review)
Review
The mechanism behind the reinstament of psychostimulant, as a major obstacle in addiction treatment is not fully understood. Controversial data are available in the literature concerning the role of the endocannabinoid (eCB) system in regulating the relapse to psychostimulant addiction in preclinical studies. The current systematic review aims to evaluate eCB modulators' effect in the reinstatement of commonly abused psychostimulants, including cocaine, amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine. By searching the PubMed, Web of Science, and Scopus databases, studies were selected. Then the studies quality was evaluated by the SYRCLE risk of bias tool. The results have still been limited to preclinical studies. Thirty-nine articles that employed self-administration and CPP as the most prevalent animal models of addiction were selected. This data indicates that cannabinoid receptor 1 antagonists and some cannabinoid receptor 2 agonists could suppress the reinstatement of cocaine and methamphetamine addiction in a dose-dependent manner. However, only AM251 was efficient to block the reinstatement of 3,4-methylenedioxymethamphetamine. In conclusion, cannabinoid receptor 1 antagonists and some cannabinoid receptor 2 agonists may have curative potential in the relapse of psychostimulant abuse. However, time, dose, and route of administration are crucial factors in their inhibitory impacts.
Topics: Animals; Endocannabinoids; N-Methyl-3,4-methylenedioxyamphetamine; Central Nervous System Stimulants; Cocaine; Methamphetamine; Amphetamine; Cannabinoid Receptor Antagonists; Recurrence; Receptors, Cannabinoid
PubMed: 36965745
DOI: 10.1016/j.ejphar.2023.175669 -
Therapeutic Advances in Cardiovascular... 2023Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon.
BACKGROUND
Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon.
OBJECTIVES
To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review.
RESULTS
Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% 52.7%, respectively; value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% 26.7%, respectively; value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine.
CONCLUSION
Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.
Topics: Humans; Adenosine; Epinephrine; Heart; No-Reflow Phenomenon; Percutaneous Coronary Intervention
PubMed: 36852839
DOI: 10.1177/17539447231154654