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Neurotoxicity Research Dec 2021Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD)...
Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), recreational MDMA use occasionally elicits hyperthermia and hyponatremia, sometimes with a fatal outcome. Specific risk factors for both adverse effects are profuse sweating while vigorously dancing under unfavorable conditions such as high ambient temperatures and insufficient fluid suppletion which result in dehydration. Concomitant use of MDMA and alcohol is highly prevalent, but adds to the existing risk, because alcohol facilitates the emergence of MDMA-induced adverse events, like hyperthermia, dehydration, and hyponatremia. Because of potential health-related consequences of concomitant use of MDMA and alcohol, it is important to identify the mechanisms of the interactions between alcohol and MDMA. This review summarizes the main drivers of MDMA-induced hyperthermia, dehydration, and hyponatremia and the role of concomitant alcohol use. It is shown that alcohol use has a profound negative impact by its interaction with most of these drivers, including poikilothermia, exposure to high ambient temperatures, heavy exercise (vigorous dancing), vasoconstriction, dehydration, and delayed initiation of sweating and diuresis. It is concluded that recreational and clinical MDMA-users should refrain from concomitant drinking of alcoholic beverages to reduce the risk for adverse health incidents when using MDMA.
Topics: Alcohol Drinking; Animals; Drug Interactions; Humans; Hyperthermia; N-Methyl-3,4-methylenedioxyamphetamine; Risk Factors
PubMed: 34554408
DOI: 10.1007/s12640-021-00416-z -
Orthopaedic Surgery Dec 2023Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta-analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery.
METHODS
Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed.
RESULTS
Nine articles of methodological quality were included in the meta-analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = -20.94 [-37.50, -4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = -34.38 [-89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p < 0.05). No publication bias was observed in any of the included studies.
CONCLUSION
Compared to general anesthesia, spinal anesthesia was associated with a lower risk of intraoperative hypotension and lower doses of ephedrine in older patients undergoing hip fracture surgery.
Topics: Humans; Aged; Ephedrine; Randomized Controlled Trials as Topic; Anesthesia, General; Hip Fractures; Hypotension; Anesthesia, Spinal
PubMed: 37753546
DOI: 10.1111/os.13895 -
BMC Emergency Medicine Aug 2023Renal dysfunction is one of the adverse effects observed in methamphetamine (MET) or tramadol abusers. In this study, we aimed to review articles involving intoxication... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Renal dysfunction is one of the adverse effects observed in methamphetamine (MET) or tramadol abusers. In this study, we aimed to review articles involving intoxication with MET or tramadol to assess the occurrence of renal dysfunction.
METHODS
Two researchers systematically searched PubMed, Scopus, Web of Sciences, and Google Scholar databases from 2000 to 2022. All articles that assessed renal function indexes including creatine, Blood Urea Nitrogen (BUN), and Creatine phosphokinase (CPK) in MET and tramadol intoxication at the time of admission in hospitals were included. We applied random effect model with Knapp-Hartung adjustment for meta-analysis using STATA.16 software and reported outcomes with pooled Weighted Mean (WM).
RESULTS
Pooled WM for BUN was 29.85 (95% CI, 21.25-38.46) in tramadol intoxication and 31.64(95% CI, 12.71-50.57) in MET intoxication. Pooled WM for creatinine in tramadol and MET intoxication was respectively 1.04 (95% CI, 0.84-1.25) and 1.35 (95% CI, 1.13-1.56). Also, pooled WM for CPK was 397.68(376.42-418.94) in tramadol and 909.87(549.98-1269.76) in MET intoxication. No significance was observed in publication bias and heterogeneity tests.
CONCLUSION
Our findings showed that tramadol or MET intoxication is associated with a considerably increased risk of renal dysfunction that may result in organ failure.
Topics: Humans; Adult; Tramadol; Methamphetamine; Kidney; Emergency Service, Hospital; Kidney Diseases
PubMed: 37568118
DOI: 10.1186/s12873-023-00855-1 -
Critical Care Medicine Mar 2020Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested that epinephrine use is associated with a worse outcome as compared with other adrenergic and nonadrenergic vasoactive drugs. We performed a systematic review and meta-analysis of randomized controlled trials to investigate the effect of epinephrine administration on outcome of critically ill patients.
DATA SOURCES
PubMed, EMBASE, and Cochrane central register were searched by two independent investigators up to March 2019.
STUDY SELECTION
Inclusion criteria were: administration of epinephrine as IV continuous infusion, patients admitted to an ICU or undergoing major surgery, and randomized controlled trials. Studies on epinephrine administration as bolus (e.g., during cardiopulmonary resuscitation), were excluded. The primary outcome was mortality at the longest follow-up available.
DATA EXTRACTION
Two independent investigators examined and extracted data from eligible trials.
DATA SYNTHESIS
A total of 5,249 studies were assessed, with a total of 12 studies (1,227 patients) finally included in the meta-analysis. The majority of the trials were performed in the setting of septic shock, and the most frequent comparator was a combination of norepinephrine plus dobutamine. We found no difference in all-cause mortality at the longest follow-up available (197/579 [34.0%] in the epinephrine group vs 219/648 [33.8%] in the control group; risk ratio = 0.95; 95% CI, 0.82-1.10; p = 0.49; I = 0%). No differences in the need for renal replacement therapy, occurrence rate of myocardial ischemia, occurrence rate of arrhythmias, and length of ICU stay were observed.
CONCLUSIONS
Current randomized evidence showed that continuous IV administration of epinephrine as inotropic/vasopressor agent is not associated with a worse outcome in critically ill patients.
Topics: Cardiovascular Diseases; Critical Illness; Dobutamine; Drug Therapy, Combination; Epinephrine; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Norepinephrine; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Shock, Septic; Vasoconstrictor Agents
PubMed: 31789701
DOI: 10.1097/CCM.0000000000004127 -
BMJ Paediatrics Open May 2024There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.
BACKGROUND
There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21 July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
INTERVENTIONS
Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.
MAIN OUTCOME MEASURES
Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).
RESULTS
15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.
CONCLUSIONS
Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
Topics: Humans; Infant, Newborn; Cardiotonic Agents; Vasoconstrictor Agents; Infant, Premature; Network Meta-Analysis; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Dobutamine
PubMed: 38769048
DOI: 10.1136/bmjpo-2024-002500 -
The Cochrane Database of Systematic... Sep 2020Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance....
BACKGROUND
Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments.
OBJECTIVES
To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of 'short cervix' and/or physical examination. History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout.
MAIN RESULTS
We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death.
AUTHORS' CONCLUSIONS
Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.
Topics: Albuterol; Analgesics, Opioid; Anti-Bacterial Agents; Bias; Cefazolin; Cerclage, Cervical; Clindamycin; Female; Humans; Indomethacin; Opium; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Stillbirth; Tocolytic Agents
PubMed: 32970845
DOI: 10.1002/14651858.CD012871.pub2 -
Clinical and Translational Medicine Jan 2022
Meta-Analysis
Topics: Alcohol Drinking; Genetic Loci; Genome-Wide Association Study; Heroin; Humans; Methamphetamine; Multifactorial Inheritance
PubMed: 35075802
DOI: 10.1002/ctm2.659 -
The Cochrane Database of Systematic... Apr 2021Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and... (Meta-Analysis)
Meta-Analysis
Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.
BACKGROUND
Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.
OBJECTIVES
To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.
SEARCH METHODS
We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was 24 February 2021.
SELECTION CRITERIA
We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.
MAIN RESULTS
Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.
Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate
PubMed: 33852162
DOI: 10.1002/14651858.CD007694.pub3