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The Cochrane Database of Systematic... Apr 2023Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological... (Review)
Review
BACKGROUND
Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.
OBJECTIVES
To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.
METHODS
The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.
MAIN RESULTS
Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention). Muscle relaxants and benzodiazepines There was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57). Opioids There was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26). There was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25). There was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11). Antidepressants There was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29).
AUTHORS' CONCLUSIONS
We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.
Topics: Adult; Humans; Acetaminophen; Low Back Pain; Tramadol; Systematic Reviews as Topic; Anti-Inflammatory Agents, Non-Steroidal; Acute Pain; Analgesics, Opioid; Buprenorphine
PubMed: 37014979
DOI: 10.1002/14651858.CD013815.pub2 -
Kidney360 May 2023Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the... (Meta-Analysis)
Meta-Analysis
Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the bleeding risk. The authors aimed to examine the association between aspirin use and bleeding during PKB. This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The article search was performed on MEDLINE and Scopus using queries specific to each database. Article inclusion was limited to primary studies. The meta-analysis compared the risk of major bleeding events between the aspirin-exposed versus nonexposed group. Pooled effect estimate was examined using random effects presented as odds ratio with 95% confidence intervals. Heterogeneity was assessed through Cochrane I 2 test statistics. Sensitivity and subgroup analyses were also performed according to kidney type. Ten studies were included in the review and four studies were included in the meta-analysis, reviewing a total of 34,067 PKBs. Definitions for significant aspirin exposure were inconsistent between studies, limiting comparisons. Studies with broader definitions for aspirin exposure mostly showed no correlation between aspirin use and postbiopsy bleeding. Studies with strict definitions for aspirin exposure found an increased risk of hemorrhagic events in the aspirin-exposed group. No significant differences were found between the aspirin-exposed and comparison groups regarding major bleeding events (odds ratio 1.72; 95% confidence interval 0.50 to 5.89, I 2 =84%). High-quality evidence on the effect of aspirin on the bleeding risk is limited. Our meta-analysis did not show a significantly increased risk of major bleeding complications in aspirin-exposed patients. Further studies are needed to define a more comprehensive approach for clinical practice.
Topics: Humans; Aspirin; Hemorrhage; Kidney; Biopsy
PubMed: 36951435
DOI: 10.34067/KID.0000000000000091 -
BMJ (Clinical Research Ed.) Mar 2023To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization's International Clinical Trials Registry Platform from database inception to 20 February 2022.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks).
DATA EXTRACTION AND SYNTHESIS
Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method.
RESULTS
98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference -26.1 (95% confidence intervals -34.0 to -18.2)), aceclofenac plus tizanidine (-26.1 (-38.5 to -13.6)), pregabalin (-24.7 (-34.6 to -14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes.
CONCLUSIONS
The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019145257.
Topics: Humans; Adult; Female; Male; Acetaminophen; Low Back Pain; Tramadol; Network Meta-Analysis; Analgesics; Acute Pain; Randomized Controlled Trials as Topic
PubMed: 36948512
DOI: 10.1136/bmj-2022-072962 -
Frontiers in Endocrinology 2023Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.
METHODS
MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).
RESULTS
Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated.
CONCLUSIONS
We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.
Topics: Humans; Aged; Clopidogrel; Aspirin; Ticlopidine; Platelet Aggregation Inhibitors; Hypoglycemia
PubMed: 36926026
DOI: 10.3389/fendo.2023.1091933 -
Arquivos de Neuro-psiquiatria Jan 2023Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent...
BACKGROUND
Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).
OBJECTIVES
To realize a systematic literature review to determine the impact of genetic variants on AR.
METHODS
Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.
RESULTS
The genetic variants rs1126643 (), rs3842787 (), rs20417 (), and rs5918 () were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance ( < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (), rs1045642 (), rs1051931 and rs7756935 (), rs2071746 (), rs1131882 and rs4523 (), rs434473 (), rs9315042 (), and rs662 (), while these differ in real interference in AR: rs5918 (), rs2243093 (), rs1330344 (), and rs20417 (). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.
CONCLUSION
It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.
Topics: Humans; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2; Pharmacogenetics; Platelet Aggregation Inhibitors; Drug Resistance
PubMed: 36918009
DOI: 10.1055/s-0042-1758445 -
The Cochrane Database of Systematic... Mar 2023Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.
OBJECTIVES
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022.
SELECTION CRITERIA
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest.
AUTHORS' CONCLUSIONS
We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
Topics: Humans; Adrenal Cortex Hormones; Aminocaproic Acid; Antifibrinolytic Agents; Aspirin; Glaucoma; Hyphema; Mydriatics; Tranexamic Acid
PubMed: 36912744
DOI: 10.1002/14651858.CD005431.pub5 -
The Cochrane Database of Systematic... Mar 2023Neonates may undergo surgery because of malformations such as diaphragmatic hernia, gastroschisis, congenital heart disease, and hypertrophic pyloric stenosis, or... (Review)
Review
BACKGROUND
Neonates may undergo surgery because of malformations such as diaphragmatic hernia, gastroschisis, congenital heart disease, and hypertrophic pyloric stenosis, or complications of prematurity, such as necrotizing enterocolitis, spontaneous intestinal perforation, and retinopathy of prematurity that require surgical treatment. Options for treatment of postoperative pain include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported. The assessment of the effects of opioids is of utmost importance, especially for neonates in substantial pain during the postoperative period.
OBJECTIVES
To evaluate the benefits and harms of systemic opioid analgesics in neonates who underwent surgery on all-cause mortality, pain, and significant neurodevelopmental disability compared to no intervention, placebo, non-pharmacological interventions, different types of opioids, or other drugs.
SEARCH METHODS
We searched Cochrane CENTRAL, MEDLINE via PubMed and CINAHL in May 2021. We searched the WHO ICTRP, clinicaltrials.gov, and ICTRP trial registries. We searched conference proceedings, and the reference lists of retrieved articles for RCTs and quasi-RCTs. SELECTION CRITERIA: We included randomized controlled trials (RCTs) conducted in preterm and term infants of a postmenstrual age up to 46 weeks and 0 days with postoperative pain where systemic opioids were compared to 1) placebo or no intervention; 2) non-pharmacological interventions; 3) different types of opioids; or 4) other drugs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods, all-cause mortality during initial hospitalization, major neurodevelopmental disability, and cognitive and educational outcomes in children more than five years old. We used the fixed-effect model with risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference (MD) for continuous data. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included four RCTs enrolling 331 infants in four countries across different continents. Most studies considered patients undergoing large or medium surgical procedures (including major thoracic or abdominal surgery), who potentially required pain control through opioid administration after surgery. The randomized trials did not consider patients undergoing minor surgery (including inguinal hernia repair) and those individuals exposed to opioids before the beginning of the trial. Two RCTs compared opioids with placebo; one fentanyl with tramadol; and one morphine with paracetamol. No meta-analyses could be performed because the included RCTs reported no more than three outcomes within the prespecified comparisons. Certainty of the evidence was very low for all outcomes due to imprecision of the estimates (downgrade by two levels) and study limitations (downgrade by one level). Comparison 1: opioids versus no treatment or placebo Two trials were included in this comparison, comparing either tramadol or tapentadol with placebo. No data were reported on the following critical outcomes: pain; major neurodevelopmental disability; or cognitive and educational outcomes in children more than five years old. The evidence is very uncertain about the effect of tramadol compared with placebo on all-cause mortality during initial hospitalization (RR 0.32, 95% Confidence Interval (CI) 0.01 to 7.70; RD -0.03, 95% CI -0.10 to 0.05, 71 participants, 1 study; I² = not applicable). No data were reported on: retinopathy of prematurity; or intraventricular hemorrhage. Comparison 2: opioids versus non-pharmacological interventions No trials were included in this comparison. Comparison 3: head-to-head comparisons of different opioids One trial comparing fentanyl with tramadol was included in this comparison. No data were reported on the following critical outcomes: pain; major neurodevelopmental disability; or cognitive and educational outcomes in children more than five years old. The evidence is very uncertain about the effect of fentanyl compared with tramadol on all-cause mortality during initial hospitalization (RR 0.99, 95% CI 0.59 to 1.64; RD 0.00, 95% CI -0.13 to 0.13, 171 participants, 1 study; I² = not applicable). No data were reported on: retinopathy of prematurity; or intraventricular hemorrhage. Comparison 4: opioids versus other analgesics and sedatives One trial comparing morphine with paracetamol was included in this comparison. The evidence is very uncertain about the effect of morphine compared with paracetamol on COMFORT pain scores (MD 0.10, 95% CI -0.85 to 1.05; 71 participants, 1 study; I² = not applicable). No data were reported on the other critical outcomes, i.e. major neurodevelopmental disability; cognitive and educational outcomes in children more than five years old, all-cause mortality during initial hospitalization; retinopathy of prematurity; or intraventricular hemorrhage.
AUTHORS' CONCLUSIONS
Limited evidence is available on opioid administration for postoperative pain in newborn infants compared to either placebo, other opioids, or paracetamol. We are uncertain whether tramadol reduces mortality compared to placebo; none of the studies reported pain scores, major neurodevelopmental disability, cognitive and educational outcomes in children older than five years old, retinopathy of prematurity, or intraventricular hemorrhage. We are uncertain whether fentanyl reduces mortality compared to tramadol; none of the studies reported pain scores, major neurodevelopmental disability, cognitive and educational outcomes in children older than five years old, retinopathy of prematurity, or intraventricular hemorrhage. We are uncertain whether morphine reduces pain compared to paracetamol; none of the studies reported major neurodevelopmental disability, cognitive and educational outcomes in children more than five years old, all-cause mortality during initial hospitalization, retinopathy of prematurity, or intraventricular hemorrhage. We identified no studies comparing opioids versus non-pharmacological interventions.
Topics: Child; Infant; Humans; Infant, Newborn; Child, Preschool; Analgesics, Opioid; Tramadol; Acetaminophen; Retinopathy of Prematurity; Analgesics; Fentanyl; Morphine; Pain, Postoperative; Cerebral Hemorrhage
PubMed: 36870076
DOI: 10.1002/14651858.CD014876.pub2 -
Annals of Noninvasive Electrocardiology... May 2023To summarize published case reports of patients diagnosed with coronavirus disease 2019 (COVID-19) and Brugada pattern electrocardiogram (ECG). (Review)
Review
AIMS
To summarize published case reports of patients diagnosed with coronavirus disease 2019 (COVID-19) and Brugada pattern electrocardiogram (ECG).
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist were followed. A literature search was conducted using PubMed, EMBASE, and Scopus up until September 2021. The incidence, clinical characteristics, and management outcomes of COVID-19 patients with a Brugada pattern ECG were identified.
RESULTS
A total of 18 cases were collected. The mean age was 47.1 years and 11.1% were women. No patients had prior confirmed diagnosis of Brugada syndrome. The most common presenting clinical symptoms were fever (83.3%), chest pain (38.8%), shortness of breath (38.8%), and syncope (16.6%). All 18 patients presented with type 1 Brugada pattern ECG. Four patients (22.2%) underwent left heart catheterization, and none demonstrated the presence of obstructive coronary disease. The most common reported therapies included antipyretics (55.5%), hydroxychloroquine (27.7%), and antibiotics (16.6%). One patient (5.5%) died during hospitalization. Three patients (16.6%) who presented with syncope received either an implantable cardioverter defibrillator or wearable cardioverter defibrillator at discharge. At follow-up, 13 patients (72.2%) had resolution of type 1 Brugada pattern ECG.
CONCLUSION
COVID-19-associated Brugada pattern ECG seems relatively rare. Most patients had resolution of the ECG pattern once their symptoms have improved. Increased awareness and timely use of antipyretics is warranted in this population.
Topics: Humans; Female; Middle Aged; Male; Antipyretics; Electrocardiography; COVID-19; Brugada Syndrome; Defibrillators, Implantable; Syncope
PubMed: 36811259
DOI: 10.1111/anec.13051 -
The Cochrane Database of Systematic... Jan 2023Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry... (Review)
Review
BACKGROUND
Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications.
OBJECTIVES
To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the use of IVIG for the treatment of KD. We included studies involving treatment for initial or refractory KD, or both.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were incidence of CAAs and incidence of any adverse effects after treatment. Our secondary outcomes were acute coronary syndromes, duration of fever, need for additional treatment, length of hospital stay, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified 31 RCTs involving a total of 4609 participants with KD. Studies compared IVIG with ASA, another dose or regimen of IVIG, prednisolone, or infliximab. The majority of studies reported on primary treatment, so those results are reported below. A limited number of studies investigated secondary or tertiary treatment in IVIG-resistant patients. Doses and regimens of IVIG infusion varied between studies, and all studies had some concerns related to risk of bias. Primary treatment with IVIG compared to ASA for people with KD Compared to ASA treatment, IVIG probably reduces the incidence of CAAs in people with KD up to 30 days (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41 to 0.87; 11 studies, 1437 participants; moderate-certainty evidence). The individual studies reported a range of adverse effects, but there was little to no difference in numbers of adverse effects between treatment groups (OR 0.57, 95% CI 0.17 to 1.89; 10 studies, 1376 participants; very low-certainty evidence). There was limited evidence for the incidence of acute coronary syndromes, so we are uncertain of any effects. Duration of fever days from treatment onset was probably shorter in the IVIG group (mean difference (MD) -4.00 days, 95% CI -5.06 to -2.93; 3 studies, 307 participants; moderate-certainty evidence). There was little or no difference between groups in need for additional treatment (OR 0.27, 95% CI 0.05 to 1.57; 3 studies, 272 participants; low-certainty evidence). No study reported length of hospital stay, and no deaths were reported in either group. Primary treatment with IVIG compared to different infusion regimens of IVIG for people with KD Higher-dose regimens of IVIG probably reduce the incidence of CAAs compared to medium- or lower-dose regimens of IVIG up to 30 days (OR 0.60, 95% CI 0.40 to 0.89; 8 studies, 1824 participants; moderate-certainty evidence). There was little to no difference in the number of adverse effects between groups (OR 1.11, 95% CI 0.52 to 2.37; 6 studies, 1659 participants; low-certainty evidence). No study reported on acute coronary syndromes. Higher-dose IVIG may reduce the duration of fever compared to medium- or lower-dose regimens (MD -0.71 days, 95% CI -1.36 to -0.06; 4 studies, 992 participants; low-certainty evidence). Higher-dose regimens may reduce the need for additional treatment (OR 0.29, 95% CI 0.10 to 0.88; 4 studies, 1125 participants; low-certainty evidence). We did not detect a clear difference in length of hospital stay between infusion regimens (MD -0.24, 95% CI -0.78 to 0.30; 3 studies, 752 participants; low-certainty evidence). One study reported mortality, and there was little to no difference detected between regimens (moderate-certainty evidence). Primary treatment with IVIG compared to prednisolone for people with KD The evidence comparing IVIG with prednisolone on incidence of CAA is very uncertain (OR 0.60, 95% CI 0.24 to 1.48; 2 studies, 140 participants; very low-certainty evidence), and there was little to no difference between groups in adverse effects (OR 4.18, 95% CI 0.19 to 89.48; 1 study; 90 participants; low-certainty evidence). We are very uncertain of the impact on duration of fever, as two studies reported this outcome differently and showed conflicting results. One study reported on acute coronary syndromes and mortality, finding little or no difference between groups (low-certainty evidence). No study reported the need for additional treatment or length of hospital stay.
AUTHORS' CONCLUSIONS
The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.
Topics: Child; Humans; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Acute Coronary Syndrome; Prednisolone; Aspirin; Inflammation; Fever
PubMed: 36695415
DOI: 10.1002/14651858.CD014884.pub2 -
Journal of Dental Research Apr 2023This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline,... (Meta-Analysis)
Meta-Analysis
This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
Topics: Adult; Humans; Acetaminophen; Ibuprofen; Oxycodone; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Pain, Postoperative; Analgesics, Opioid; Tooth Extraction; Acute Pain
PubMed: 36631957
DOI: 10.1177/00220345221139230