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The Cochrane Database of Systematic... Oct 2020Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
OBJECTIVES
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded.
DATA COLLECTION AND ANALYSIS
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
MAIN RESULTS
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
AUTHORS' CONCLUSIONS
We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).
Topics: Adult; Anesthesia, General; Antiemetics; Drug Therapy, Combination; Female; Humans; Male; Network Meta-Analysis; Placebos; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33075160
DOI: 10.1002/14651858.CD012859.pub2 -
Gastroenterology Apr 2023Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety are unknown. We evaluated this in a network meta-analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety are unknown. We evaluated this in a network meta-analysis of randomized controlled trials (RCTs).
METHODS
We searched the literature to September 7, 2022. We judged the efficacy of drugs based on global symptoms of gastroparesis; individual symptoms, including nausea, vomiting, abdominal pain, bloating, or fullness; and safety according to total adverse events and adverse events leading to withdrawal. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of not improving with 95% confidence intervals (CIs), ranking drugs according to P-score.
RESULTS
We identified 29 RCTs (3772 patients). Based on global symptoms, clebopride ranked first for efficacy (RR, 0.30; 95% CI, 0.16-0.57; P-score = .99) followed by domperidone (RR, 0.68; 95% CI, 0.48-0.98; P-score = .76). No other drug was superior to placebo. Only 2 drug classes were efficacious: in rank order, oral dopamine antagonists (RR, 0.58; 95% CI, 0.44-0.77; P-score = .96) and tachykinin-1 antagonists (RR, 0.69; 95% CI, 0.52-0.93; P-score = .83). For individual symptoms, oral metoclopramide ranked first for nausea (RR 0.46; 95% CI, 0.21-1.00; P-score = .95), fullness (RR 0.67; 95% CI, 0.35-1.28; P-score = .86), and bloating (RR 0.53; 95% CI, 0.30-0.93; P-score = .97), based on only 1 small trial. Only prucalopride was more likely to be associated with adverse events than placebo.
CONCLUSIONS
In a network meta-analysis, oral dopamine antagonists and tachykinin-1 antagonists were more efficacious than placebo for gastroparesis, but confidence in the evidence was low to moderate for most comparisons. There is an unmet need for efficacious therapies for gastroparesis.
Topics: Humans; Gastroparesis; Network Meta-Analysis; Nausea; Dopamine Antagonists; Tachykinins
PubMed: 36581089
DOI: 10.1053/j.gastro.2022.12.014 -
Dysphagia Oct 2020Dysphagia is associated with increased risk of stroke-associated pneumonia (SAP). However, it is unclear what other factors contribute to that risk or which measures may... (Review)
Review
Dysphagia is associated with increased risk of stroke-associated pneumonia (SAP). However, it is unclear what other factors contribute to that risk or which measures may reduce it. This systematic review aimed to provide evidence on interventions and care processes associated with SAP in patients with dysphagia. Studies were screened for inclusion if they included dysphagia only patients, dysphagia and non-dysphagia patients or unselected patients that included dysphagic patients and evaluated factors associated with a recorded frequency of SAP. Electronic databases were searched from inception to February 2017. Eligible studies were critically appraised. Heterogeneity was evaluated using I. The primary outcome was SAP. Eleven studies were included. Sample sizes ranged from 60 to 1088 patients. There was heterogeneity in study design. Measures of immunodepression are associated with SAP in dysphagic patients. There is insufficient evidence to justify screening for aerobic Gram-negative bacteria. Prophylactic antibiotics did not prevent SAP and proton pump inhibitors may increase risk. Treatment with metoclopramide may reduce SAP risk. Evidence that nasogastric tube (NGT) placement increases risk of SAP is equivocal. A multidisciplinary team approach and instrumental assessment of swallowing may reduce risk of pneumonia. Patients with impaired mobility were associated with increased risk. Findings should be interpreted with caution given the number of studies, heterogeneity and descriptive analyses. Several medical interventions and care processes, which may reduce risk of SAP in patients with dysphagia, have been identified. Further research is needed to evaluate the role of these interventions and care processes in clinical practice.
Topics: Deglutition; Deglutition Disorders; Humans; Pneumonia; Risk Factors; Stroke; Stroke Rehabilitation
PubMed: 31493069
DOI: 10.1007/s00455-019-10061-6 -
The Cochrane Database of Systematic... May 2020Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.
OBJECTIVES
To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.
MAIN RESULTS
Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.
AUTHORS' CONCLUSIONS
Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.
Topics: Administration, Oral; Body Weight; Breast Feeding; Domperidone; Female; Galactogogues; Humans; Infant; Infant, Newborn; Lactation; Metoclopramide; Milk, Human; Mothers; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Sulpiride; Thyrotropin-Releasing Hormone
PubMed: 32421208
DOI: 10.1002/14651858.CD011505.pub2 -
BMC Neurology Jun 2023Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. (Meta-Analysis)
Meta-Analysis
The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.
METHODS
We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.
RESULTS
Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.
CONCLUSION
A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.
Topics: Humans; Metoclopramide; Sumatriptan; Network Meta-Analysis; Prochlorperazine; Chlorpromazine; Granisetron; Valproic Acid; Ketorolac; Randomized Controlled Trials as Topic; Migraine Disorders; Nausea; Headache
PubMed: 37291500
DOI: 10.1186/s12883-023-03259-7 -
Drugs in R&D Mar 2023Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis.
METHODS
We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI).
RESULTS
We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs.
CONCLUSIONS
The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions.
REGISTRATION
PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).
Topics: Adult; Child; Humans; Domperidone; Metoclopramide; Gastroparesis; Dopamine Antagonists
PubMed: 36749528
DOI: 10.1007/s40268-023-00413-x -
Drugs & Aging Dec 2023To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent. (Review)
Review
BACKGROUND
To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent.
OBJECTIVE
This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades.
RESULTS
A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide.
CONCLUSIONS
In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce.
Topics: Humans; Health Personnel; Drug-Related Side Effects and Adverse Reactions
PubMed: 37863868
DOI: 10.1007/s40266-023-01072-y -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
Journal of Dental Anesthesia and Pain... Oct 2021Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of... (Review)
Review
BACKGROUND
Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine.
METHODS
An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines.
RESULTS
The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study.
CONCLUSION
Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.
PubMed: 34703891
DOI: 10.17245/jdapm.2021.21.5.413 -
General Hospital Psychiatry 2024Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions.
METHODS
Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection.
FINDINGS
17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24 months), the combined prevalence of mental health conditions and brain fog was 20·4% (95% CI 11·1%-34·4%), being lower among those previously hospitalised than in community-managed patients(19·5 vs 29·7% respectively; p = 0·047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p = ·000).
CONCLUSIONS
Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.
Topics: Adult; Humans; Post-Acute COVID-19 Syndrome; Mental Health; Prevalence; COVID-19; SARS-CoV-2; Mental Fatigue
PubMed: 38447388
DOI: 10.1016/j.genhosppsych.2024.02.009