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Medicine Oct 2023Zavegepant nasal spray is a novel CGRP receptor antagonist that has been developed for the acute treatment of migraine - a prevalent disease leading to disability and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Zavegepant nasal spray is a novel CGRP receptor antagonist that has been developed for the acute treatment of migraine - a prevalent disease leading to disability and economic burden. The meta-analysis aims to quantify the efficacy of Zavegepant compared to standard care or placebo in achieving pain freedom, freedom from most bothersome symptoms (MBS), sustained pain freedom, and pain relapse at 2 to 48 hours.
METHODS
Databases and registers were systematically searched to identify relevant clinical trials. Two independent reviewers used a standardized data extraction form to collect relevant data on primary and secondary outcomes. Statistical analysis was performed in RevMan 5.4 software. The efficacy of Zavegepant was compared to placebo using odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic, chi-square test, Z value, and P value. Cochrane ROB-2 and ROBINS-I tools were used to assess the biases (osf.io/b32ne).
RESULTS
Of 36 identified studies, 3 were included in this meta-analysis. Zavegepant was more effective in achieving pain freedom (OR: 1.6, P < .00001), and freedom from MBS at 2 hours (OR = 1.4, P < .00001). The intervention group demonstrated a higher likelihood of sustained pain freedom between 2 and 48 hours (OR = 1.74, P < .00001). Although there was a trend towards reduced pain relapse between 2 and 48 hours in the intervention group, the difference was insignificant (OR = 0.67, P = .11).
CONCLUSION
This meta-analysis confirms the effectiveness of Zavegepant nasal spray in treating acute migraine, with significant improvements in pain and symptom relief. Further research is needed to determine the effect on pain relapse and overall safety.
Topics: Humans; Nasal Sprays; Treatment Outcome; Double-Blind Method; Neoplasm Recurrence, Local; Migraine Disorders; Analgesics; Pain; Recurrence
PubMed: 37904462
DOI: 10.1097/MD.0000000000035632 -
Acta Psychiatrica Scandinavica Dec 2023Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging...
BACKGROUND
Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality.
METHODS
Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales.
RESULTS
Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported.
CONCLUSION
This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.
Topics: Humans; Antipsychotic Agents; Clozapine; Schizophrenia; Risperidone; Paliperidone Palmitate; Delayed-Action Preparations
PubMed: 37899506
DOI: 10.1111/acps.13621 -
BMC Oral Health Oct 2023Periodontal pockets are characteristic of periodontitis. Scaling and root planing is the gold standard for periodontitis treatment. Additional local antimicrobials are... (Meta-Analysis)
Meta-Analysis
Periodontal pockets are characteristic of periodontitis. Scaling and root planing is the gold standard for periodontitis treatment. Additional local antimicrobials are recommended in patients with a probing depth of ≥ 5 mm. This study aims to determine the effectiveness of chlorhexidine compared to other local antimicrobials in periodontitis. Searches were conducted using the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines. Meta-analysis was performed on studies that met inclusion criteria after risk of bias assessment. Meta-analysis between chlorhexidine chips and other antimicrobials showed a mean difference in probing depth after one month of 0.58 mm (p < 0.00001) whereas after three months the mean difference in probing depth was 0.50 mm (p = 0.001), index plaque 0.01 (p = 0.94) and gingival index - 0.11 mm (p = 0.02). Between chlorhexidine gel and other antimicrobials showed a mean difference in probing depth of 0.40 mm (p = 0.30), plaque index of 0.20 mm (p = 0.0008) and gingival index of -0.04 mm (p = 0.83) after one month. Chlorhexidine chips were more effective on the gingival index than other antimicrobials after three months. The other antimicrobials were more effective than chlorhexidine chips on probing depth after one and three months, and than chlorhexidine gels on plaque index after one month.
Topics: Humans; Chlorhexidine; Root Planing; Anti-Infective Agents, Local; Dental Scaling; Periodontitis; Gels
PubMed: 37899443
DOI: 10.1186/s12903-023-03241-2 -
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 -
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 -
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 -
Journal of Psychopharmacology (Oxford,... Oct 2023Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations.
AIMS
We hypothesized that QTP-IR is inferior to QTP-ER at any dose in efficacy for the acute treatment in schizophrenia and tested using a dose-response model-based network meta-analysis (NMA).
METHODS
We searched PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov for randomized placebo-controlled trials comparing QTP-IR and/or QTP-ER for acute psychosis in patients with schizophrenia up to September 21, 2022. A random effect Bayesian dose-response model-based NMA was performed to compare the dose-response relationships between QTP-IR and QTP-ER.
RESULTS
The relationship between doses and antipsychotic effects was partially bell-shaped for QTP-IR but not for QTP-ER. The respective peak effect dose was 279.7 mg for QTP-IR and 557.2 mg for QTP-ER, with no significant difference in peak effect. QTP-IR ranging from 100 to 300 mg were significantly superior to QTP-ER at the same doses. In addition, QTP-IR ranging from 100 to 400 mg were significantly better than placebo, whereas QTP-ER ranging from 500 to 800 mg were significantly more effective than placebo. Moreover, QTP-IR 600 mg was significantly less effective than QTP-ER at the same dose. Furthermore, QTP-IR 700 mg was significantly superior to placebo, but significantly inferior to QTP-ER 600 mg.
CONCLUSIONS
QTP-IR may reach comparable peak responses and exhibit enhanced antipsychotic effects at lower doses than QTP-ER; the converse may be true at relatively high doses. Collectively, we propose a novel strategy to enhance the efficacy of QTP administration.
Topics: Humans; Quetiapine Fumarate; Antipsychotic Agents; Network Meta-Analysis; Bayes Theorem; Psychotic Disorders; Schizophrenia; Delayed-Action Preparations
PubMed: 37740667
DOI: 10.1177/02698811231200020 -
Clinical Nutrition ESPEN Oct 2023The exploration of lipid-lowering resources, such as phytosterols, for the complementary nutritional treatment of hypercholesterolemia is relevant to reduce...
BACKGROUND
The exploration of lipid-lowering resources, such as phytosterols, for the complementary nutritional treatment of hypercholesterolemia is relevant to reduce cardiovascular risk. The use of phytosterols in capsules or tablets can bring advantages in the context of diet therapy, but such format is still less studied when compared to fortified foods.
OBJECTIVE
Systematically review randomized clinical trials on the effects of phytosterol supplementation, in capsules or tablets, on the lipid profile and its use in the treatment of hypercholesterolemia in adults.
DESIGN
A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, with a PROSPERO protocol registered under number CRD42021249539. The process was conducted by two independent reviewers. Only randomized clinical trials with phytosterol supplementation in adult individuals with hypercholesterolemia were included. The terms were searched in the databases: PubMed/MEDLINE, Cochrane Library/CENTRAL, Embase, LILACS and Web of Science, without restriction of time and language. The manual search was also performed through the list of references of articles included in this review.
RESULTS
The searches resulted in 977 articles. 22 articles were selected, whose full text was read, and according to the eligibility criteria 10 were incorporated into the review. The studies were separated into groups according to the association of the intervention with changes in lifestyle and the characteristics extracted from the studies were summarized and displayed in tables. Most studies have revealed a positive association between phytosterol supplementation and cholesterol reduction, despite the short duration of interventions.
CONCLUSION
The analyzed studies showed that phytosterol supplements can be useful to modulate the lipid profile, helping to reduce the plasma concentration of LDL cholesterol. However, more research with the aforementioned supplementation in such pharmaceutical formats should be encouraged.
Topics: Adult; Humans; Hypercholesterolemia; Phytosterols; Capsules; Randomized Controlled Trials as Topic; Tablets; Dietary Supplements
PubMed: 37739728
DOI: 10.1016/j.clnesp.2023.08.022 -
The Cochrane Database of Systematic... Sep 2023Ocular discomfort is the leading cause of permanent discontinuation of soft contact lens (SCL) wear. Silicone hydrogel and hydrogel materials are the two major... (Review)
Review
BACKGROUND
Ocular discomfort is the leading cause of permanent discontinuation of soft contact lens (SCL) wear. Silicone hydrogel and hydrogel materials are the two major categories of SCLs, with silicone hydrogel materials being newer and more breathable than hydrogel materials. Whether comfort is associated with SCL material is controversial despite numerous studies. Similarly, the difference between these materials in terms of safety outcomes (e.g. frequency of microbial keratitis) is unclear.
OBJECTIVES
To evaluate the comparative effectiveness and safety of silicone hydrogel compared with hydrogel SCLs on self-reported comfort, dry eye test results, and adverse events in SCL-wearing adults 18 years of age or older.
SEARCH METHODS
The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials (RCTs). There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We also searched the reference lists of identified studies, review articles, and guidelines for information about relevant studies that may not have been identified by our search strategy. Furthermore, we contacted investigators regarding ongoing trials. The most recent database search was conducted on 24 June 2022.
SELECTION CRITERIA
Our search selection criteria included RCTs, quasi-RCTs, and cross-over RCTs.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included seven parallel-group RCTs conducted in the USA, the UK, Australia, Germany, India, and Turkey. A total of 1371 participants were randomized. The duration of SCL wear ranged from one to 52 weeks. Study characteristics and risk of bias The median number of participants per trial was 120 (interquartile range: 51 to 314), and the average age ranged from 20.7 to 33.0 years. Women represented the majority of participants (range 55% to 74.9%; 5 RCTs). Collectively, the included trials compared eight different silicone hydrogel SCLs with three different hydrogel SCLs. Five trials compared daily disposable SCLs, and two compared extended wear SCLs (worn for seven days and six nights). New SCL wearers were enrolled in three trials. Two trials included both new and established SCL wearers, and two trials did not report participants' history of SCL use. Five trials were sponsored by industry. We judged the overall risk of bias to be 'high' or 'some concerns' for the safety and efficacy outcomes. Findings One trial reported Ocular Surface Disease Index (OSDI) results, with the evidence being very uncertain about the effects of SCL material on OSDI scores (mean difference -1.20, 95% confidence interval [CI] -10.49 to 8.09; 1 RCT, 47 participants; very low certainty evidence). Three trials reported visual analog scale comfort score results, with no clear difference in comfort between materials, but the evidence was of very low certainty; trial results could not be combined because the three trials reported results at different time points. The evidence is very uncertain about the effect of SCL material on discontinuation of contact lens wear (risk ratio [RR] 0.64, 95% CI 0.11 to 3.74; 1 RCT, 248 participants). None of the included trials reported Contact Lens Dry Eye Questionnaire (CLDEQ-8) or Standard Patient Evaluation of Eye Dryness (SPEED) scores. There was no evidence of a clinically meaningful difference (> 0.5 unit) between daily disposable silicone hydrogel and hydrogel SCLs in corneal staining, conjunctival staining, or conjunctival redness (very low certainty evidence). Adverse events Very low certainty evidence from two trials comparing daily disposable SCLs suggested no evidence of a difference between lens materials in the risk of vision-threatening adverse events at one to four weeks (RR 0.68, 95% CI 0.08 to 5.51; 2 RCTs, 368 participants). Two trials comparing extended wear SCLs indicated that hydrogel SCLs may have a 2.03 times lower risk of adverse events at 52 weeks compared with silicone hydrogel SCLs (RR 2.03, 95% CI 1.38 to 2.99; 815 participants), but the certainty of evidence was very low.
AUTHORS' CONCLUSIONS
The overall evidence for a difference between all included silicone hydrogel and hydrogel SCLs was of very low certainty, with most trials at high overall risk of bias. The majority of studies did not assess comfort using a validated instrument. There was insufficient evidence to support recommending one SCL material over the other. For extended wear, hydrogel SCL may have a lower risk of adverse events at 52 weeks compared to silicon hydrogel. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.
Topics: Adult; Female; Humans; Adolescent; Young Adult; Silicones; Hydrogels; Face; Contact Lenses, Hydrophilic; Patient Reported Outcome Measures; Randomized Controlled Trials as Topic
PubMed: 37724689
DOI: 10.1002/14651858.CD014791.pub2 -
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