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Respiratory Medicine and Research Jun 2024This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants.
METHOD
Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed.
RESULTS
Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments.
CONCLUSION
These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.
Topics: Humans; Bronchopulmonary Dysplasia; Administration, Inhalation; Infant, Newborn; Infant, Premature; Budesonide; Beclomethasone; Fluticasone; Treatment Outcome; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic; Ductus Arteriosus, Patent; Female; Male; Pulmonary Surfactants
PubMed: 38744231
DOI: 10.1016/j.resmer.2024.101096 -
Drug Development and Industrial Pharmacy May 2024TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug... (Review)
Review
OBJECTIVE
TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug solubility, permeability, and delivery. The main objective of the present article is to review these advantages of TheDES.
SIGNIFICANCE
TheDES show unique properties, such as low toxicity, biodegradability, improved bioavailability and enhanced drug delivery of poorly soluble active pharmaceutical ingredients. They are also biocompatible in nature which makes them a promising candidate for various therapeutic applications, including drug formulations, drug delivery and other biomedical uses. The development and utilization of TheDES shows significant advancement in pharmaceutical research, providing new opportunities for improving drug delivery.
METHODS
The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to demonstrate the effectiveness of TheDES in enhancing drug solubility, permeability, and delivery. All chosen articles were selected considering their significance, quality, and approach to addressing issues.
RESULT
As a result, various TheDES were identified that can be formulated in different ways: one component can act as a vehicle for an API, either HBD or HBA can be an API, both HBD and HBA can be APIs, or the individual components of DES are not therapeutically active but the resulting DES possesses therapeutic activity. Additionally, TheDES were also recognized to enhance drug delivery and solubility for different APIs, including NSAIDs, anesthetic drugs, antifungals, and others.
Topics: Solubility; Deep Eutectic Solvents; Drug Delivery Systems; Permeability; Humans; Drug Compounding; Hydrogen Bonding; Chemistry, Pharmaceutical; Biological Availability; Pharmaceutical Preparations; Solvents
PubMed: 38634708
DOI: 10.1080/03639045.2024.2345131 -
Journal of Drugs in Dermatology : JDD Apr 2024Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined.
METHODS
A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values. Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle).
CONCLUSIONS
Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.8148.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Acne Vulgaris; Network Meta-Analysis; Drug Combinations; Adapalene, Benzoyl Peroxide Drug Combination; Treatment Outcome; Gels
PubMed: 38564399
DOI: 10.36849/JDD.8148 -
Biomedicines Feb 2024In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to... (Review)
Review
In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to alleviate the symptoms of PD retardation or halt the progression of the disease itself. This systematic review aims to critically update some of the most promising novel treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations and future directions in PD research. Gene therapy in PD is encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, and neuronal circuits in animal and clinical trials. A promising approach to targeted drug delivery for PD involves the use of nanotechnology to create drug delivery vehicles that can traverse the blood-brain barrier and deliver medications specifically to the regions of the brain affected by PD. Neuroprotective agents are compounds that have the ability to protect neurons from degeneration and death, and they hold great promise for the evolution of disease-modifying treatments for PD. Magnetic field therapy is a promising non-invasive method that promotes neural plasticity in PD. The establishment of standardized protocols for animal and human studies, safety, ethical considerations, and cost-effectiveness are the major challenges for the future research of novel PD therapies. The development of novel therapies for PD represents a promising path toward to effective personalized disease-modifying treatments for PD.
PubMed: 38540162
DOI: 10.3390/biomedicines12030549 -
Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.Oral Diseases Mar 2024This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the... (Review)
Review
OBJECTIVES
This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis.
MATERIALS AND METHODS
The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis.
RESULTS
A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I = 73.271) efficacy.
CONCLUSIONS
Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.
PubMed: 38523365
DOI: 10.1111/odi.14928 -
Wounds : a Compendium of Clinical... Feb 2024Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound...
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
Topics: Humans; Phenytoin; Anti-Bacterial Agents; Wound Healing; Analgesics; Pain
PubMed: 38479432
DOI: No ID Found -
European Neuropsychopharmacology : the... Apr 2024Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA).... (Meta-Analysis)
Meta-Analysis
Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.
Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.
Topics: Humans; Hypnotics and Sedatives; Zolpidem; Network Meta-Analysis; Automobile Driving; Psychomotor Performance; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Piperazines; Azabicyclo Compounds
PubMed: 38401406
DOI: 10.1016/j.euroneuro.2024.01.011 -
European Journal of Dermatology : EJD Oct 2023This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate... (Meta-Analysis)
Meta-Analysis
This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15th, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5th, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator's Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.
Topics: Child; Humans; Tacrolimus; Dermatitis, Atopic; Dermatologic Agents; Immunoglobulin A; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38297923
DOI: 10.1684/ejd.2023.4556 -
Addiction Biology Jan 2024Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers... (Review)
Review
Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers are frequently employed to detect Δ9-tetrahydrocannabinol (THC) consumption among drivers during roadside tests, despite not necessarily indicating impairment. Characterising THC-specific alterations to oculomotor behaviour may offer a more sensitive measure for indexing drug-related impairment, necessitating discrimination between acute THC effects, chronic use and potential tolerance effects. The present review aims to synthesise current evidence on the acute and chronic effects of THC on driving-relevant oculomotor behaviour. The review was prospectively registered (10.17605/OSF.IO/A4H9W), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines informed reporting standards. Overall, 20 included articles comprising 12 experimental acute dosing trials, 5 cross-sectional chronic use studies and 3 roadside epidemiological studies examined the effects of cannabis/THC on oculomotor parameters including saccadic activity gaze behaviour, nystagmus, smooth pursuit and eyelid/blink characteristics. Acute THC consumption selectively impacts oculomotor control, notably increasing saccadic latency and inaccuracy and impairing inhibitory control. Chronic cannabis users, especially those with early age of use onset, display enduring oculomotor deficits that affect visual scanning efficiency. The presence of eyelid tremors appears to be a reliable indicator of cannabis consumption while remaining distinct from direct impairment associated with visual attention and motor control. Cannabis selectively influences oculomotor activity relevant to driving, highlighting the role of cannabinoid systems in these processes. Defining cannabis/THC-specific changes in oculomotor control may enhance the precision of roadside impairment assessments and vehicle safety systems to detect drug-related impairment and assess driving fitness.
Topics: Cannabis; Dronabinol; Cross-Sectional Studies; Cannabinoids; Cannabinoid Receptor Agonists
PubMed: 38221807
DOI: 10.1111/adb.13359 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6