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The Journal of Headache and Pain Sep 2023Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients.
METHODS
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model.
CONCLUSIONS
Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects.
Topics: Adult; Humans; Nasal Sprays; Network Meta-Analysis; Migraine Disorders; Oxazolidinones
PubMed: 37723470
DOI: 10.1186/s10194-023-01662-6 -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
Advances in Nutrition (Bethesda, Md.) Jan 2024Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high... (Meta-Analysis)
Meta-Analysis Review
Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.
BACKGROUND
Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies.
OBJECTIVE
This study aimed to compare more frequently dosed vitamin D2 and vitamin D3 in improving total 25(OH)D and determine the concomitant effect of response modifiers on heterogeneity, and secondly, to compare the vitamin D2-associated change in 25(OH)D2 with the vitamin D3-associated change in 25(OH)D3.
METHODS
PubMed, EMBASE, Cochrane, and the Web of Science Core collection were searched for randomized controlled trials of vitamin D2 compared with vitamin D3, daily or once/twice weekly dosed. After screening for eligibility, relevant data were extracted for meta-analyses to determine the standardized mean difference when different methods of 25(OH)D analyses were used. Otherwise, the weighted mean difference (WMD) was determined.
RESULTS
Overall, the results based on 20 comparative studies showed vitamin D3 to be superior to vitamin D2 in raising total 25(OH)D concentrations, but vitamin D2 and vitamin D3 had a similar positive impact on their corresponding 25(OH)D hydroxylated forms. The WMD in change in total 25(OH)D based on 12 daily dosed vitamin D2-vitamin D3 comparisons, analyzed using liquid chromatography-tandem mass spectrometry, was 10.39 nmol/L (40%) lower for the vitamin D2 group compared with the vitamin D3 group (95% confidence interval: -14.62, -6.16; I = 64%; P < 00001). Body mass index (BMI) appeared to be the strongest response modifier, reducing heterogeneity to 0% in both subgroups. The vitamin D2- and vitamin D3-induced change in total 25(OH)D lost significance predominantly in subjects with a BMI >25 kg/m (P = 0.99). However, information on BMI was only available in 13/17 daily dosed comparisons.
CONCLUSIONS
Vitamin D3 leads to a greater increase of 25(OH)D than vitamin D2, even if limited to daily dose studies, but vitamin D2 and vitamin D3 had similar positive impacts on their corresponding 25(OH)D hydroxylated forms. Next to baseline 25(OH)D concentration, BMI should be considered when comparing the effect of daily vitamin D2 and vitamin D3 supplementation on total 25(OH)D concentration. This study was registered in PROSPERO as CRD42021272674.
Topics: Humans; Body Mass Index; Cholecalciferol; Dietary Supplements; Ergocalciferols; Vitamin D; Vitamin D Deficiency
PubMed: 37865222
DOI: 10.1016/j.advnut.2023.09.016 -
Pharmacy (Basel, Switzerland) Oct 2023The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges... (Review)
Review
The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges regarding the oral administration of medicine to inpatients in a variety of healthcare settings such as (1) hospitals, (2) nursing homes and (3) long-term stay units (LTSUs). A literature search was undertaken in September 2021 and repeated in June 2023 in the following databases: PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, PsycINFO and ProQuest. A Microsoft Excel spreadsheet was devised to collate the following data from each eligible study: study author and year, country, number of participants, title, duration (follow-up period), study design, inclusion and exclusion criteria, method and data collection, relevant outcomes, and key findings. A total of 3023 records were identified, with 12 articles being included in the final systematic review. Seven of the twelve studies reported on the prevalence of difficulties swallowing SODFs, which varied from 10-34.2%. Nine of the twelve studies reported the methods used to manipulate SODFs, with the most reported method being tablet crushing. Given the prevalence of swallowing difficulties and the subsequent crushing of medicines in response to this, it is evident that concerns should be raised regarding the potential for a medication administration error to occur.
PubMed: 37888511
DOI: 10.3390/pharmacy11050167 -
BMJ (Clinical Research Ed.) May 2024To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
DATA SYNTHESIS AND STUDY QUALITY
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
ELIGIBILITY CRITERIA
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
RESULTS
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
CONCLUSION
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023388065.
Topics: Humans; Antidepressive Agents; Depression; Hallucinogens; Psilocybin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38692686
DOI: 10.1136/bmj-2023-078084 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as... (Review)
Review
BACKGROUND
Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans.
METHODS
Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots.
RESULTS
Sixteen eligible articles, including k = 5 studies of pain tolerance ( = 210), k = 5 studies of pain threshold ( = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges' g = 0.28, 95% CI = 0-0.55, Z = 1.99, = 0.05) and pain tolerance (Hedges' g = 0.32, 95% CI = 0.05-0.59, Z = 2.30, = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of -0.37 (95% CI = -0.77 to 0.03, Z = -1.80) but with no statistical significance ( = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges' g = 0.37, 95% CI = 0.29-0.64, Z = 5.33, < 0.01).
CONCLUSION
These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
PubMed: 38139792
DOI: 10.3390/ph16121665 -
Pharmaceutics Jul 2023The colour of a product plays an important role in consumer experiences, and in the context of pharmaceutical products, this could potentially affect a patient's... (Review)
Review
The colour of a product plays an important role in consumer experiences, and in the context of pharmaceutical products, this could potentially affect a patient's expectations, behaviours, and adherence. Several studies have been conducted on adults, but little is known about children's opinions on colours of medicines and to what extent medicines' colour affects their acceptability. To address this gap, a systematic search in PubMed, Scopus, MEDLINE, and Web of Science was conducted. Two authors independently screened the titles, abstracts, and references of all articles and selected studies conducted on children (0-18 years old), assessing children's preferences or opinions about colour of oral dosage forms as either a primary or secondary objective or as an anecdotal record. A total of 989 publications were identified and, after screening, 18 publications were included in the review. Red and pink were the most liked colours and there appeared to be a relationship between the colour of a medicine and expected taste/flavour. The review also highlighted a scarcity of information, usually collected as an anecdotal record. Several gaps in the current knowledge were underlined, emphasizing the need of patient-centred studies to understand if the use of certain colours can improve or worsen the acceptability of a paediatric medicine. This will help inform pharmaceutical manufacturers and regulators on the role and need of colours in children's medicines beyond quality purposes.
PubMed: 37514178
DOI: 10.3390/pharmaceutics15071992 -
Iranian Journal of Medical Sciences Sep 2023Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease that affects oral mucosa. The coating agents, topical analgesics, and topical steroids are... (Review)
Review
BACKGROUND
Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease that affects oral mucosa. The coating agents, topical analgesics, and topical steroids are usually used as treatment methods. has been used for RAS treatment based on its anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, a systemic review on the therapeutic effect of topical licorice on RAS management was performed.
METHODS
Science Direct, Scopus, Cochrane databases, PubMed Google Scholar, and ResearchGate were searched up to September 2021 to find all English randomized clinical trials studying the effect of , or its compositions on RAS. Meta-analysis was not conducted because of data heterogeneity. Articles were reviewed qualitatively, and only those with a Jadad score ≥3 were included. Animal studies, , review papers, non-English papers, and case reports were excluded.
RESULTS
Six studies with 314 subjects were included after screening. The result showed licorice has significant effects on RAS pain reduction, ulcer size, and healing time. Its effectiveness is related to its dose-dependent anti-inflammatory and antioxidant effects through several mechanisms. It also has antibacterial effects against and as another mechanism of action in RAS treatment. In addition, licorice can elevate the epidermal growth factor (EGF) level compared to the control group, which has an essential role in oral mucosal tissue integrity.
CONCLUSION
Licorice extract has been used in different dosage forms, including paste, patch, and mouthwash with concentrations of 1% or 5%. The healing time after licorice therapy is expected to be within 4-8 days. Licorice did not show any adverse effect in the intervention groups, indicating its effectiveness and safety in RAS treatment.
Topics: Animals; Humans; Stomatitis, Aphthous; Glycyrrhiza; Anti-Inflammatory Agents
PubMed: 37786470
DOI: 10.30476/IJMS.2022.94467.2576 -
American Journal of Cardiovascular... Jul 2023Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its intranasal spray formulation has a rapid onset of action and shows promise for the unsupervised treatment of PSVT.
OBJECTIVE
We aimed to evaluate the efficacy and safety of etripamil nasal spray for the acute conversion of PSVT.
METHODS
A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching the PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane databases through to 1 December 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI).
RESULTS
Three RCTs with a total of 496 participants were included in our analysis. Etripamil was effective for PSVT conversion at 15 min (RR 1.84, 95% CI 1.37-2.48), 30 min (RR 1.86, 95% CI 1.42-2.44), and 60 min (RR 1.25, 95% CI 1.05-1.50) after drug administration; decreasing medical intervention-seeking (RR 0.58, 95% CI 0.37-0.90); and decreasing emergency room (ER) visits (RR 0.61, 95% CI 0.38-0.97). However, there was no difference at 300 min (RR 1.10, 95% CI 0.97-1.25) and it was associated with higher rates of adverse events (RR 3.17, 95% CI 2.15-4.69).
CONCLUSION
Etripamil nasal spray was effective and well tolerated to induce PSVT termination for up to 60 min. Therefore, etripamil nasal spray constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.
Topics: Humans; Nasal Sprays; Randomized Controlled Trials as Topic; Benzoates; Tachycardia, Ventricular
PubMed: 37351813
DOI: 10.1007/s40256-023-00592-7 -
European Neuropsychopharmacology : the... Jun 2024Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment... (Meta-Analysis)
Meta-Analysis Review
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
Topics: Humans; Antipsychotic Agents; Administration, Oral; Schizophrenia; Delayed-Action Preparations; Network Meta-Analysis; Randomized Controlled Trials as Topic; Injections; Treatment Outcome
PubMed: 38490016
DOI: 10.1016/j.euroneuro.2024.03.003