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Clinical and Experimental Medicine Dec 2023This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science,... (Meta-Analysis)
Meta-Analysis Review
This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science, Cochrane Central, and Google Scholar were searched from inception until September 3, 2023. Studies comparing the diagnostic performance of FIT between medicine users and non-users in average-risk colorectal cancer screening populations were included. Pooled sensitivity, specificity, and positive predictive values (PPVs) for advanced neoplasia (AN) of FIT were compared by reporting pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. Twenty-two studies enrolling 5,572,367 individuals were included. For aspirin, pooled sensitivity and specificity for AN were 57.2% and 88.4% in users versus 60.2% and 93.2% in non-users; while pooled ORs were 1.49 (95% CI 0.89-2.48, P = 0.13) and 0.72 (95% CI 0.62-0.83, P < 0.001), respectively. In subgroup analysis, there was no difference in sensitivity and specificity between the two groups at the cutoff of 20 μg Hb/g (P = 0.57 and 0.29, respectively) but a significantly lower specificity in users compared with non-users at lower cutoffs (P < 0.001). Moreover, a significantly lower PPV in users compared with non-users was observed after matching age and sex confounders (P = 0.001). Warfarin had no significant influence on PPV of FIT (P = 0.43). PPIs were associated with a significantly lower PPV in users (P < 0.001). Aspirin use was associated with lower specificity and PPV of FIT. Aspirin discontinuation before FIT to reduce false-positive results should be interpreted with caution given concerns about cardiovascular events. Increasing cutoff values of FIT in aspirin users may be another possible approach. Additionally, warfarin withdrawal before FIT is unnecessary but PPIs withdrawal before FIT is recommended to reduce false-positive results.
Topics: Humans; Aspirin; Warfarin; Proton Pump Inhibitors; Early Detection of Cancer; Colorectal Neoplasms; Colonoscopy
PubMed: 37804359
DOI: 10.1007/s10238-023-01196-w -
The Cochrane Database of Systematic... Aug 2023Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental... (Review)
Review
BACKGROUND
Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental outcomes. Studies have shown a reduction in changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in neonates experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for analgesia. This is an update of a review first published in 2006 and updated in 2012.
OBJECTIVES
The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries (ICTRP, ISRCTN and clinicaltrials.gov) in August 2022; searches were limited from 2011 forwards. We checked the reference lists of included studies and relevant systematic reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates. We included both term (≥ 37 completed weeks postmenstrual age) and preterm infants (< 37 completed weeks' postmenstrual age) up to a maximum of 44 weeks' postmenstrual age. The study must have reported on either physiological markers of pain or validated pain scores.
DATA COLLECTION AND ANALYSIS
We assessed the methodological quality of the trials using the information provided in the studies and by personal communication with the authors. We extracted data on relevant outcomes, estimated the effect size and reported this as a mean difference (MD). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Of the 66 included studies, 36 evaluated breastfeeding, 29 evaluated supplemental breast milk and one study compared them against each other. The procedures conducted in the studies were: heel lance (39), venipuncture (11), intramuscular vaccination (nine), eye examination for retinopathy of prematurity (four), suctioning (four) and adhesive tape removal as procedure (one). We noted marked heterogeneity in the control interventions and pain assessment measures amongst the studies. Since many studies included multiple arms with breastfeeding/supplemental breast milk as the main comparator, we were not able to synthesise all interventions together. Individual interventions are compared to breastfeeding/supplemental breast milk and reported. The numbers of studies/participants presented with the findings are not taken from pooled analyses (as is usual in Cochrane Reviews), but are the overall totals in each comparison. Overall, the included studies were at low risk of bias except for masking of intervention and outcome assessment, where nearly one-third of studies were at high risk of bias. Breastfeeding versus control Breastfeeding may reduce the increase in heart rate compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration of sucrose/glucose (20% to 33%) with skin-to-skin contact (low-certainty evidence, 8 studies, 784 participants). Breastfeeding likely reduces the duration of crying compared to no intervention, lying on table, rocking, heel warming, holding by mother, skin-to-skin contact, bottle feeding mother's milk and moderate concentration of glucose (moderate-certainty evidence, 16 studies, 1866 participants). Breastfeeding may reduce percentage time crying compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration sucrose and moderate concentration of sucrose with skin-to-skin contact (low-certainty evidence, 4 studies, 359 participants). Breastfeeding likely reduces the Neonatal Infant Pain Scale (NIPS) score compared to no intervention, holding by mother, heel warming, music, EMLA cream, moderate glucose concentration, swaddling, swaddling and holding (moderate-certainty evidence, 12 studies, 1432 participants). Breastfeeding may reduce the Neonatal Facial Coding System (NFCS) score compared to no intervention, holding, pacifier and moderate concentration of glucose (low-certainty evidence, 2 studies, 235 participants). Breastfeeding may reduce the Douleur Aigue Nouveau-né (DAN) score compared to positioning, holding or placebo (low-certainty evidence, 4 studies, 709 participants). In the majority of the other comparisons there was little or no difference between the breastfeeding and control group in any of the outcome measures. Supplemental breast milk versus control Supplemental breast milk may reduce the increase in heart rate compared to water or no intervention (low-certainty evidence, 5 studies, 336 participants). Supplemental breast milk likely reduces the duration of crying compared to positioning, massage or placebo (moderate-certainty evidence, 11 studies, 1283 participants). Supplemental breast milk results in little or no difference in percentage time crying compared to placebo or glycine (low-certainty evidence, 1 study, 70 participants). Supplemental breast milk results in little or no difference in NIPS score compared to no intervention, pacifier, moderate concentration of sucrose, eye drops, gentle touch and verbal comfort, and breast milk odour and verbal comfort (low-certainty evidence, 3 studies, 291 participants). Supplemental breast milk may reduce NFCS score compared to glycine (overall low-certainty evidence, 1 study, 40 participants). DAN scores were lower when compared to massage and water; no different when compared to no intervention, EMLA and moderate concentration of sucrose; and higher when compared to rocking or pacifier (low-certainty evidence, 2 studies, 224 participants). Due to the high number of comparator interventions, other measures of pain were assessed in a very small number of studies in both comparisons, rendering the evidence of low certainty. The majority of studies did not report on adverse events, considering the benign nature of the intervention. Those that reported on adverse events identified none in any participants. Subgroup analyses were not conducted due to the small number of studies.
AUTHORS' CONCLUSIONS
Moderate-/low-certainty evidence suggests that breastfeeding or supplemental breast milk may reduce pain in neonates undergoing painful procedures compared to no intervention/positioning/holding or placebo or non-pharmacological interventions. Low-certainty evidence suggests that moderate concentration (20% to 33%) glucose/sucrose may lead to little or no difference in reducing pain compared to breastfeeding. The effectiveness of breast milk for painful procedures should be studied in the preterm population, as there are currently a limited number of studies that have assessed its effectiveness in this population.
Topics: Female; Infant; Infant, Newborn; Humans; Milk, Human; Breast Feeding; Pain, Procedural; Pain; Acetaminophen
PubMed: 37643989
DOI: 10.1002/14651858.CD004950.pub4 -
Clinical Reviews in Allergy & Immunology Oct 2023Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are... (Review)
Review
Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are unclear. We conducted a comprehensive review of environmental risk, protective factors, and biomarkers for AR to establish the evidence hierarchy. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to December 31, 2022. We calculated summary effect estimate (odds ratio (OR), relative risk (RR), hazard ratio (HR), and standardized mean difference (SMD)), 95% confidence interval, random effects p value, I statistic, 95% prediction interval, small study effects, and excess significance biases, and stratification of the level of evidence. Methodological quality was assessed by AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). We retrieved 4478 articles, of which 43 met the inclusion criteria. The 43 eligible articles identified 31 potential environmental risk factors (10,806,206 total population, two study not reported), 11 potential environmental protective factors (823,883 total population), and 34 potential biomarkers (158,716 total population) for meta-analyses. The credibility of evidence was convincing (class I) for tic disorders (OR = 2.89, 95% CI 2.11-3.95); and highly suggestive (class II) for early-life antibiotic use (OR = 3.73, 95% CI 3.06-4.55), exposure to indoor dampness (OR = 1.49, 95% CI 1.27-1.75), acetaminophen exposure (OR = 1.54, 95% CI 1.41-1.69), childhood acid suppressant use (OR = 1.40, 95% CI 1.23-1.59), exposure to indoor mold (OR = 1.66, 95% CI 1.26-2.18), coronavirus disease 2019 (OR = 0.11, 95% CI 0.06-0.22), and prolonged breastfeeding (OR = 0.72, 95% CI 0.65-0.79). This study is registered in PROSPERO (CRD42022384320).
Topics: Child; Humans; Acetaminophen; Biomarkers; COVID-19; Protective Factors; Rhinitis, Allergic; Risk Factors; Systematic Reviews as Topic
PubMed: 37490237
DOI: 10.1007/s12016-023-08964-2 -
European Journal of Surgical Oncology :... Oct 2023Breast Cancer (BC) is the most common cancer amongst women. The chemo-preventative effects of aspirin on breast cancer have been demonstrated in several longitudinal... (Meta-Analysis)
Meta-Analysis Review
Breast Cancer (BC) is the most common cancer amongst women. The chemo-preventative effects of aspirin on breast cancer have been demonstrated in several longitudinal studies however previous meta-analysis have shown inconsistent results. This study aimed to assess the relationship between aspirin use and BC risk, and to determine if there is a dose-response relationship between aspirin and BC risk. Studies incorporating BC risk with aspirin use published within the last twenty years were included. The study report is based on the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology. Twenty-eight cohort studies that reported BC incidence during a follow up of 4.4-32 years were included. Compared to non-users, aspirin users had a reduced risk of BC (HR = 0.91, c.i 0.81-0.97, p = 0.002). There was no obvious association between BC risk reduction and aspirin dose (HR = 0.94, c.i 0.85-1.04) or duration (HR = 0.86, c.i 0.71-1.03). Frequency, however, was associated with a reduced risk of BC (HR = 0.90, c.i 0.82-0.98). A risk reduction was observed in oestrogen receptor (ER) positive tumours (HR = 0.90, c.i 0.86-0.96, p = 0.0004) while no relationship was observed with ER negative tumours (HR = 0.94, c.i 0.85-1.05). This meta-analysis found an association between aspirin intake and BC risk reduction. A more favourable outcome was noted with ingestion of greater than 6 tablets of aspirin per week. Aspirin had a significant risk reduction in patients with ER positive tumours compared to ER negative BC.
Topics: Humans; Female; Aspirin; Breast Neoplasms; Risk; Cohort Studies; Incidence; Observational Studies as Topic
PubMed: 37321932
DOI: 10.1016/j.ejso.2023.05.015 -
United European Gastroenterology Journal Nov 2023Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated.
METHODS
We searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta-analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non-users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) was also performed.
RESULTS
Twelve studies with 341,063 participants were included in this meta-analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16-1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56-6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49-1.80]; HR [95% CI] = 6.55 [2.01-21.33]). In the bleeding site-specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30-1.84]).
CONCLUSIONS
PPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.
Topics: Humans; Proton Pump Inhibitors; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Gastrointestinal Hemorrhage; Colorectal Neoplasms
PubMed: 37553807
DOI: 10.1002/ueg2.12448 -
Fitoterapia Jan 2024Black cohosh, also known as Cimicifuga sp., is one of the most widely used ethnomedicine for the treatment of major health issues in women. Some reports show that... (Review)
Review
ETHNOPHARMACOLOGICAL USES
Black cohosh, also known as Cimicifuga sp., is one of the most widely used ethnomedicine for the treatment of major health issues in women. Some reports show that Cimicifuga sp. exhibit anti-cancer, anti-viral, anti-microbial, anti-pyretic, and anti-inflammatory properties.
PURPOSE OF THIS REVIEW
The objective of this comprehensive review is to furnish current and exhaustive knowledge pertaining to the pharmacological, phytochemical, and therapeutic properties of Cimicifuga sp.
MATERIALS AND METHODS
In this review, all the available information was collected on Cimicifugasp. via computerized search using Google Scholar, PubMed, Research Gate, Sci-Hub, supplementary resources (books, government reports, and Ph.D. theses).
RESULT
The phytochemical investigation on Cimicifuga sp. has shown phytoconstituents such as triterpenoid glycosides, phenylpropanoid, flavonoids, saponin, lignan, nitrogenous compounds, alkaloids, 4α-Methyl steroids and some other component like monoterpene lactones cimicifugolides A-C etc. Cimicifuga conveys a wide scope of research on in-vitro and in-vivo pharmacological potential, like anti-cancer, anti-microbial, anti-viral, anti-inflammatory, estrogenic, anti-oxidant, anti-neoplastic, anti-depressant, anti-Alzheimer, and anti-climacteric properties.
CONCLUSION
This article discusses the medicinal and traditional histories of various Cimicifuga species. Because quality control and safety assessments of Cimicifuga species are currently lacking, only a limited portion of the plant may be used as medication. The majority of current research focuses on triterpene glycosides. Although there are a variety of additional molecules that may have novel biological functions, systematic investigations of these compounds are lacking. The Cimicifuga plant has to go through a lot of studies before it can be completely used in clinics as a viable medicinal contender.
Topics: Female; Humans; Actaea; Anti-Inflammatory Agents; Antiviral Agents; Cimicifuga; Ethnopharmacology; Glycosides; Molecular Structure; Phytochemicals; Phytotherapy; Plant Extracts
PubMed: 38052334
DOI: 10.1016/j.fitote.2023.105767 -
Translational Stroke Research Dec 2023There is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug... (Meta-Analysis)
Meta-Analysis
There is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug use and the risk of aSAH. We searched PubMed and Scopus from the databases' inception until December 2021. Observational studies reporting the association between any drug therapy and aSAH were included. The odds ratios (ORs) for each drug used in aSAH were meta-analyzed with a random-effect model. According to the systematic review, 25 observational studies were eligible for the present study. Four therapeutic purpose-based classes (e.g., lipid-lowering agents) and 14 mechanism-based classes (e.g., statins) were meta-analyzed. Anti-hypertensive agents (OR, 0.50; 95% confidence interval [95% CI], 0.33-0.74), statins (OR, 0.55; 95% CI, 0.35-0.85), biguanides (OR, 0.57; 95% CI, 0.34-0.96), and acetylsalicylic acid (ASA) (OR, 0.62; 95% CI, 0.41-0.94) were inversely associated with the risk of aSAH. Non-ASA non-steroidal anti-inflammatory drugs (OR, 1.73; 95% CI, 1.07-2.79), selective cyclooxygenase-2 inhibitors (OR, 2.04; 95% CI, 1.24-3.35), vitamin K antagonists (OR, 1.50; 95% CI, 1.18-1.91), and dipyridamole (OR, 1.77; 95% CI, 1.23-2.54) were positively associated with the incidence of aSAH. There was also a trend toward a positive association between glucocorticoids (OR, 1.38; 95% CI, 0.97-1.94) and aSAH. The present study suggests that anti-hypertensive agents, statins, biguanides, and ASA are candidate drugs for preventing aSAH. By contrast, several drugs (e.g., anti-thrombotic drugs) may increase the risk of aSAH. Thus, the indications of these drugs in patients with intracranial aneurysms should be carefully determined.
Topics: Humans; Subarachnoid Hemorrhage; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antihypertensive Agents; Intracranial Aneurysm; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Biguanides
PubMed: 36242746
DOI: 10.1007/s12975-022-01097-2 -
Scientific Reports Dec 2023Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache... (Meta-Analysis)
Meta-Analysis
Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache Disorders. TTH is treated with over-the-counter medications, mostly paracetamol or ibuprofen. The purpose was to assess the effectiveness of paracetamol versus ibuprofen in treating episodic tension-type headache (ETTH) through direct and indirect comparisons of randomized controlled trials (RCTs). We included RCTs comparing paracetamol with a placebo, ibuprofen with a placebo, or paracetamol with ibuprofen for acute ETTH treatment that were published between 1988 and 2022. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Web of Science. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias. We identified 14 studies including 6521 people with ETTH. None of the studies had a low risk of bias for all domains; this was most likely due to inadequate reporting and a small sample size. Ibuprofen (odds ratio (OR): 1.73, 95% confidence interval (CI): 1.17-2.56) showed better efficacy than paracetamol (OR: 1.62, 95% CI 1.24-2.13) for pain-free status at 2 h, while paracetamol (OR: 1.42, 95% CI 0.87-2.30) showed better efficacy than ibuprofen (OR: 1.20, 95% CI 0.58-2.48) for pain-free status at 1 h. Paracetamol was associated with the lowest likelihood of rescue medication use (OR: 0.49, 95% CI 0.37-0.65). Ibuprofen was associated with a lower likelihood of the occurrence of any events and gastrointestinal adverse events compared with placebo and paracetamol (OR: 0.95, 95% CI 0.64-1.41 and OR: 0.81, 95% CI 0.44-1.50, respectively). Paracetamol and ibuprofen showed better efficacy than placebo in treating ETTH; there was no statistically significant difference in efficacy between the two drugs. For individuals at a higher risk (like renal insufficiency or risk of GI bleeding), paracetamol may be considered as a preferred option instead of Ibuprofen. Further meta-analyses of head-to-head trials are needed for direct comparisons in the future.PROSPERO registration number: CRD42022340936.
Topics: Humans; Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Tension-Type Headache; Network Meta-Analysis
PubMed: 38057585
DOI: 10.1038/s41598-023-48910-y -
Journal of Medicinal Food Nov 2023The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines,... (Review)
Review
The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including and models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.
Topics: Rats; Animals; Stomach Ulcer; Antioxidants; Fruit; Gastric Mucosa; Plant Extracts; Rats, Wistar; Anti-Ulcer Agents; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Aspirin
PubMed: 37902784
DOI: 10.1089/jmf.2023.0005 -
The Cochrane Database of Systematic... Aug 2023Acute otitis media (AOM) is one of the most common childhood infectious diseases. Pain is the key symptom of AOM and central to children's and parents' experience of the... (Review)
Review
BACKGROUND
Acute otitis media (AOM) is one of the most common childhood infectious diseases. Pain is the key symptom of AOM and central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management. This is an update of a review first published in 2016.
OBJECTIVES
Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs as compared with paracetamol in children with AOM.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 5, April 2023; MEDLINE (Ovid, from 1946 to May 2023), Embase (from 1947 to May 2023), CINAHL (from 1981 to May 2023), LILACS (from 1982 to May 2023), and Web of Science Core Collection (from 1955 to May 2023). We searched the WHO ICTRP and ClinicalTrials.gov for completed and ongoing trials (23 May 2023).
SELECTION CRITERIA
We included randomised controlled trials comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in non-hospitalised children aged six months to 16 years with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. We extracted and summarised data for the following comparisons: paracetamol versus placebo, NSAIDs versus placebo, NSAIDs versus paracetamol, and NSAIDs plus paracetamol versus paracetamol alone.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We rated the overall certainty of evidence for each outcome of interest using the GRADE approach.
MAIN RESULTS
We included four trials (411 children) which were assessed at low to high risk of bias. Paracetamol versus placebo Data from one trial (148 children) informed this comparison. Paracetamol may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 10% versus 25%, risk ratio (RR) 0.38, 95% confidence interval (CI) 0.17 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 7; low-certainty evidence). The evidence is very uncertain about the effects of paracetamol on fever at 48 hours (RR 1.03, 95% CI 0.07 to 16.12; very low-certainty evidence) and adverse events (RR 1.03, 95% CI 0.21 to 4.93; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus placebo Data from one trial (146 children) informed this comparison. Ibuprofen may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6; low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen on fever at 48 hours (RR 1.06, 95% CI 0.07 to 16.57; very low-certainty evidence) and adverse events (RR 1.76, 95% CI 0.44 to 7.10; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus paracetamol Data from four trials (411 children) informed this comparison. The evidence is very uncertain about the effect of ibuprofen versus paracetamol in relieving ear pain at 24 hours (RR 0.83, 95% CI 0.59 to 1.18; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 0.91, 95% CI 0.54 to 1.54; 3 RCTs, 183 children; low-certainty evidence); and four to seven days (RR 0.74, 95% CI 0.17 to 3.23; 2 RCTs, 38 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on mean pain score at 24 hours (0.29 lower, 95% CI 0.79 lower to 0.20 higher; 3 RCTs, 111 children; very low-certainty evidence); 48 to 72 hours (0.25 lower, 95% CI 0.66 lower to 0.16 higher; 3 RCTs, 108 children; very low-certainty evidence); and four to seven days (0.30 higher, 95% CI 1.78 lower to 2.38 higher; 2 RCTs, 31 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol in resolving fever at 24 hours (RR 0.69, 95% CI 0.24 to 2.00; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 1.18, 95% CI 0.31 to 4.44; 3 RCTs, 182 children; low-certainty evidence); and four to seven days (RR 2.75, 95% CI 0.12 to 60.70; 2 RCTs, 39 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on adverse events (RR 1.71, 95% CI 0.43 to 6.90; 3 RCTs, 281 children; very low-certainty evidence); reconsultations (RR 1.13, 95% CI 0.92 to 1.40; 1 RCT, 53 children; very low-certainty evidence); and delayed antibiotic prescriptions (RR 1.32, 95% CI 0.74 to 2.35; 1 RCT, 53 children; very low-certainty evidence). No data were available on time to resolution of pain. NSAIDs plus paracetamol versus paracetamol alone Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two trials that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates, therefore we were unable to draw any firm conclusions (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Despite explicit guideline recommendations on the use of analgesics in children with AOM, the current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in children with AOM is limited. Paracetamol and ibuprofen as monotherapies may be more effective than placebo in relieving short-term ear pain in children with AOM. The evidence is very uncertain for the effect of ibuprofen versus paracetamol on relieving short-term ear pain in children with AOM, as well as for the effectiveness of ibuprofen plus paracetamol versus paracetamol alone, thereby preventing any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.
Topics: Child; Humans; Acetaminophen; Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal; Pain; Fever; Anti-Bacterial Agents; Otitis Media
PubMed: 37594020
DOI: 10.1002/14651858.CD011534.pub3