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The American Journal of Emergency... Nov 2020Vasopressors are mainstay treatment for patients in shock and are usually infused through central venous catheters (CVCs). However, CVCs are associated with risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasopressors are mainstay treatment for patients in shock and are usually infused through central venous catheters (CVCs). However, CVCs are associated with risk of infection or delay from the needs of confirmation of placement. Infusing vasopressor through peripheral venous catheter (PIVs) could be an alternative in the Emergency Departments (ED) but data regarding complications is inconclusive. We performed a random-effects meta-analysis to assess literature involving prevalence of complications from infusing vasopressors via PIVs.
METHODS
We searched PubMed, EMBASE and Scopus databases from beginnings to 02/02/2020 to identify relevant randomized control trials, cohort, case-control studies. We excluded case reports. Authors assessed studies' quality with Newcastle-Ottawa Scale and Cochrane Risk of Bias tool. Kappa score was used to assess interrater agreement. Outcome was complications as direct results from infusing vasopressors through PIVs.
RESULTS
We identified 325 articles and included 9 studies after reviewing 16 full text articles. Our analysis included 1835 patients whose mean age was 63 (Standard Deviation 12) years and 48% was female. There were 122 (7%) complications, of which 117 (96%) were minor. The meta-analysis with random effects showed the pooled prevalence of complications as 0.086 (95%CI 0.031-0.21). Studies reporting infusion safety guidelines had significantly lower prevalence of complications (0.029, 95%CI 0.018-0.045), compared to those not reporting a safety guideline (0.12, 95%CI 0.038-0.30, p = 0.024).
CONCLUSION
There was low prevalence of complications as a direct result from infusing vasopressors through PIVs. Studies with safety guidelines were associated with significantly lower prevalence of complications. Further studies are needed to confirm our observations.
Topics: Catheterization, Central Venous; Catheterization, Peripheral; Central Venous Catheters; Emergency Service, Hospital; Erythema; Extravasation of Diagnostic and Therapeutic Materials; Humans; Infusions, Intravenous; Intensive Care Units; Practice Guidelines as Topic; Shock; Time-to-Treatment; Vasoconstrictor Agents; Venous Thrombosis
PubMed: 33039229
DOI: 10.1016/j.ajem.2020.09.047 -
Chest Aug 2023Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed.
RESEARCH QUESTION
What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?
STUDY DESIGN AND METHODS
In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome.
RESULTS
We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85).
INTERPRETATION
Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm.
TRIAL REGISTRY
Center for Open Science: https://osf.io/arxwq.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Network Meta-Analysis; Epinephrine; Vasopressins; Resuscitation; Cardiopulmonary Resuscitation; Emergency Medical Services
PubMed: 36736487
DOI: 10.1016/j.chest.2023.01.033 -
Anaesthesia Jan 2020Spinal anaesthesia for caesarean section commonly causes maternal hypotension. This systematic review and network meta-analysis compared methods to prevent hypotension... (Meta-Analysis)
Meta-Analysis
Spinal anaesthesia for caesarean section commonly causes maternal hypotension. This systematic review and network meta-analysis compared methods to prevent hypotension in women receiving spinal anaesthesia for caesarean section. We selected randomised controlled trials that compared an intervention to prevent hypotension with another intervention or inactive control by searching MEDLINE and Embase, Web of Science to December 2018. There was no language restriction. Two reviewers extracted data on trial characteristics, methods and outcomes. We assessed risk of bias for individual trials (Cochrane tool) and quality of evidence (GRADE checklist). We assessed 109 trials (8561 women) and 12 different methods that resulted in 30 direct comparisons. Methods ranked by OR (95%CI) from most effective to least effective were: metaraminol 0.11 (0.04-0.26); norepinephrine 0.13 (0.06-0.28); phenylephrine 0.18 (0.11-0.29); leg compression 0.25 (0.14-0.43); ephedrine 0.28 (0.18-0.43); colloid given before induction of anaesthesia 0.38 (0.24-0.61); angiotensin 2, 0.12 (0.02-0.75); colloid given after induction of anaesthesia 0.52 (0.30-0.90); mephentermine 0.09 (0.01-1.30); crystalloid given after induction of anaesthesia 0.78 (0.46-1.31); and crystalloid given before induction of anaesthesia 1.16 (0.76-1.79). Phenylephrine caused maternal bradycardia compared with control, OR (95%CI) 0.23 (0.07-0.79). Ephedrine lowered umbilical artery pH more than phenylephrine, standardised mean difference (95%CI) 0.78 (0.47-1.49). We conclude that vasopressors should be given to healthy women to prevent hypotension during caesarean section with spinal anaesthesia.
Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Female; Humans; Hypotension; Pregnancy; Randomized Controlled Trials as Topic; Vasoconstrictor Agents
PubMed: 31531852
DOI: 10.1111/anae.14841 -
The British Journal of Dermatology Jul 2019Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
BACKGROUND
Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
OBJECTIVES
To update our systematic review on interventions for rosacea.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence.
RESULTS
We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach.
CONCLUSIONS
For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Brimonidine Tartrate; Combined Modality Therapy; Dermatologic Agents; Dermatology; Drug Therapy, Combination; Evidence-Based Medicine; Facial Dermatoses; Humans; Intense Pulsed Light Therapy; Low-Level Light Therapy; Oxymetazoline; Randomized Controlled Trials as Topic; Rosacea; Severity of Illness Index; Treatment Outcome
PubMed: 30585305
DOI: 10.1111/bjd.17590 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
Journal of Drugs in Dermatology : JDD Jan 2022Actinic Keratosis (AK) is a premalignant lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Topical 5-Fluorouracil (5-FU) and imiquimod have been used...
BACKGROUND
Actinic Keratosis (AK) is a premalignant lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Topical 5-Fluorouracil (5-FU) and imiquimod have been used for field-directed therapy for AK; however, their use is limited by intolerable skin reactions and long treatment durations.
OBJECTIVE
To assess current data on the efficacy, tolerability, and long-term effectiveness of topical calcipotriol plus 5-FU combination for the field-directed therapy of AK. The systematic review will include a critical evaluation of the available evidence.
METHODS
A systematic review of the literature was performed in August 2021 using the EMBASE and MEDLINE databases. Studies that assess the use of calcipotriol and 5-FU to treat actinic keratosis (AK) and cSCC prevention were included.
RESULTS
In total, four studies met the inclusion criteria. Our final analysis included three articles. One clinical trial evaluated the efficacy of calcipotriol plus 5-FU in treating AK. Another clinical trial evaluated the long-term effect of calcipotriol plus 5-FU in prevention of cSCC. A retrospective study evaluated the use of calcipotriol plus 5-FU with cryotherapy.
LIMITATIONS
A limitation of this systematic review is the limited number of clinical trials that examine the combination of 5-FU plus calcipotriol in treating AK. The active control arm (Petroleum jelly plus 5-FU combination) is not equivalent to topical 5-FU monotherapy; hence, no superiority claim can be made vs topical 5-FU in terms of efficacy.
CONCLUSION
Calcipotriol plus 5-FU reduced greater number of AKs in the treated area (25 cm2) when compared to 5-FU plus petroleum jelly, but only 27% of participants had complete clearance on the face at week-8. Calcipotriol plus 5-FU lowered the risk of cSCC on the face and scalp area over a 3-year period. Adequate and well-controlled studies are needed to compare the efficacy of calcipotriol plus 5-FU to 5-FU monotherapy, and other FDA-approved topical drugs such as imiquimod cream and tirbanibulin ointment. J Drugs Dermatol. 2022;21(1):60-65. doi:10.36849/JDD.6632.
Topics: Acetamides; Calcitriol; Carcinoma, Squamous Cell; Fluorouracil; Humans; Keratosis, Actinic; Morpholines; Pyridines; Retrospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 35005863
DOI: 10.36849/JDD.2022.6632 -
The International Journal on Drug Policy Jan 2019'Chemsex' is the use of drugs before or during planned sexual events to facilitate, enhance, prolong and sustain the experience. Drugs associated with chemsex are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
'Chemsex' is the use of drugs before or during planned sexual events to facilitate, enhance, prolong and sustain the experience. Drugs associated with chemsex are methamphetamine, GHB/GBL, mephedrone, cocaine and ketamine. This review syntheses published research on the antecedents, behaviours and consequences associated with chemsex behaviours among men who have sex with men (MSM).
METHODS
Papers from high income countries which were published between January 2000 and September 2018 reporting the use of chemsex drugs before or during sex were identified through Medline, Web of Science, CINAHL and Central. Results were synthesised using a narrative approach and conceptualised using a behavioural analysis framework.
RESULTS
The search identified 2492 publications, of which 38 were included in the final synthesis. There were wide variations in chemsex prevalence estimates due to the heterogeneous sampling in the studies. Chemsex participants have expectations that the drugs will positively affect their sexual encounters and HIV positive MSM are more likely to engage in the behaviour than HIV negative MSM. There were wide ranging prevalence estimates on injecting drugs for sexual purposes and the sharing of injecting equipment with some evidence of unsafe injecting practices. Participants were more likely to engage in condomless anal intercourse than men who do not engage in chemsex. This may increase the risk of transmission for HIV and other sexually transmitted infections.
CONCLUSION
A minority of MSM appear to engage in chemsex behaviours but they are at risk of this negatively impacting on their health and well-being. Further research is required to examine high risk chemsex behaviours, impact of chemsex on psycho-social well-being and if chemsex influences uptake of PrEP, PEP and sexual health screening.
Topics: 4-Butyrolactone; Cocaine; HIV Infections; Homosexuality, Male; Humans; Illicit Drugs; Ketamine; Male; Methamphetamine; Prevalence; Risk-Taking; Sexually Transmitted Diseases; Substance-Related Disorders; Unsafe Sex
PubMed: 30513473
DOI: 10.1016/j.drugpo.2018.11.014 -
Intensive Care Medicine Jun 2019We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and... (Meta-Analysis)
Meta-Analysis
PURPOSE
We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and in pre-defined subgroups.
METHODS
Our pre-specified study protocol is published on PROSPERO, CRD42017071698. We identified randomised clinical trials up to January 2019 investigating vasopressin therapy versus any other vasoactive comparator in adults with septic shock. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed as well as one-stage regression models with single treatment covariate interactions for subgroup analyses.
RESULTS
Four trials were included with a total of 1453 patients. For the primary outcomes, there was no effect of vasopressin on 28-day mortality [relative risk (RR) 0.98, 95% CI 0.86-1.12] or serious adverse events (RR 1.02, 95% CI 0.82-1.26). Vasopressin led to more digital ischaemia [absolute risk difference (ARD) 1.7%, 95% CI 0.3%-3.2%] but fewer arrhythmias (ARD - 2.8%, 95% CI - 0.2% to - 5.3%). Mesenteric ischaemia and acute coronary syndrome events were similar between groups. Vasopressin reduced the requirement for renal replacement therapy (RRT) (RR 0.86, 95% CI 0.74-0.99), but this finding was not robust to sensitivity analyses. There were no statistically significant interactions in the pre-defined subgroups (baseline kidney injury severity, baseline lactate, baseline norepinephrine requirement and time to study inclusion).
CONCLUSIONS
Vasopressin therapy in septic shock had no effect on 28-day mortality although the confidence intervals are wide. It appears safe but with a different side effect profile from norepinephrine. The finding on reduced RRT should be interpreted cautiously. Future trials should focus on long-term outcomes in select patient groups as well as incorporating cost effectiveness analyses regarding possible reduced RRT use.
Topics: APACHE; Aged; Female; Humans; Length of Stay; Male; Middle Aged; Randomized Controlled Trials as Topic; Shock, Septic; Survivors; Vasoconstrictor Agents; Vasopressins
PubMed: 31062052
DOI: 10.1007/s00134-019-05620-2 -
Forensic Science International Sep 2022Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides... (Review)
Review
Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Humans; Methamphetamine; Suicide
PubMed: 35908335
DOI: 10.1016/j.forsciint.2022.111391 -
Sleep Medicine Reviews Aug 2023Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA... (Meta-Analysis)
Meta-Analysis Review
Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.
Topics: Humans; Male; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Continuous Positive Airway Pressure; Norepinephrine
PubMed: 37423095
DOI: 10.1016/j.smrv.2023.101809