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Italian Journal of Dermatology and... Feb 2023Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of the combination of cryotherapy and photodynamic modalities with imiquimod in patients with actinic keratosis: a systematic review and meta-analysis.
INTRODUCTION
Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic modalities with imiquimod has been proven to be a potential therapeutic option for AKs. However, there is no comprehensive systematic study that discussed this concept in literature taking into consideration both efficacy and safety.
EVIDENCE ACQUISITION
We performed a comprehensive search of the literature for studies assessing the efficacy and toxicity of the combinatorial tripartite regimen, consisting of cryotherapy and photodynamic modalities with imiquimod in AK. Metanalysis was performed using comprehensive meta-analysis version 3.0.
EVIDENCE SYNTHESIS
After the screening of 1031 studies, five studies were included. Two trials compared the effect of imiquimod/cryotherapy versus cryotherapy alone or versus cryotherapy/vehicle. Our meta-analysis indicated that imiquimod/cryotherapy effectively induces complete clinical clearance in patients with AKs (OR: 6.26; 95%CI: 1.56-24.1; P=0.01). Moreover, another two studies, which were not meta-analyzed, indicated a substantial clinical clearance in the number of AK lesions in the imiquimod plus photodynamic therapy arm as compared to 5% imiquimod or PDT alone. No serious systemic adverse events were reported in all the treatment arms.
CONCLUSIONS
Combined PDT or cryotherapy with imiquimod is more effective in the complete recovery of AK than treatment with imiquimod alone.
Topics: Humans; Imiquimod; Keratosis, Actinic; Aminoquinolines; Treatment Outcome; Cryotherapy
PubMed: 36799007
DOI: 10.23736/S2784-8671.22.07461-8 -
Nanoscale Advances Jan 2023: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and... (Review)
Review
: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). : We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. : A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. : This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.
PubMed: 36756502
DOI: 10.1039/d2na00483f -
The Journal of Dermatology Apr 2023Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth... (Review)
Review
Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection.
Topics: Humans; Microinjections; Skin; Administration, Cutaneous; Drug Delivery Systems; Epidermis; Needles; Pain
PubMed: 36700529
DOI: 10.1111/1346-8138.16732 -
The Annals of Pharmacotherapy Sep 2023To assess the efficacy, safety, and clinical application of tretinoin 0.1%-benzoyl peroxide 3% cream for the topical treatment of acne vulgaris. (Review)
Review
OBJECTIVE
To assess the efficacy, safety, and clinical application of tretinoin 0.1%-benzoyl peroxide 3% cream for the topical treatment of acne vulgaris.
DATA SOURCES
A systematic review of the literature was performed using the terms OR OR in MEDLINE (PubMed) and EMBASE. ClinicalTrials.gov was searched to obtain completed clinical trial results not published elsewhere.
STUDY SELECTION AND DATA EXTRACTION
All human studies published in English prior to November 2022 related to pharmacology, clinical trials, safety, and efficacy were evaluated for inclusion.
DATA SYNTHESIS
In two 12-week, phase 3, randomized, vehicle-controlled clinical trials, tretinoin 0.1%-benzoyl peroxide 3% cream significantly reduced inflammatory and noninflammatory facial acne lesions and significantly improved Investigator Global Assessment (IGA) rating to clear or almost clear. The cream has a suitable safety profile, with application site pain and dryness as the most common adverse events.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS
Tretinoin-BPO had similar IGA success compared to other topical retinoid and retinoid-BPO treatments for acne vulgaris. Compared to individual tretinoin and benzoyl peroxide therapy, the combination product streamlines application, which will improve medication adherence; however, the cost of tretinoin-BPO cream may be prohibitive.
CONCLUSIONS
Tretinoin 0.1%-benzoyl peroxide 3% cream is safe and effective for the treatment of moderate-to-severe acne. Long-term trial data on efficacy and tolerability are not yet available.
Topics: Humans; Acne Vulgaris; Benzoyl Peroxide; Dermatologic Agents; Gels; Immunoglobulin A; Retinoids; Treatment Outcome; Tretinoin
PubMed: 36639853
DOI: 10.1177/10600280221147338 -
Nanotheranostics 2023Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy....
Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications.
Topics: Drug Carriers; Drug Delivery Systems; Nanoparticles; Porosity; Silicon Dioxide; Tissue Distribution
PubMed: 36593800
DOI: 10.7150/ntno.77395 -
Frontiers in Psychiatry 2022Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes...
Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant.
STUDY OBJECTIVES
Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.
METHODS
We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.
RESULTS
Our search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.
CONCLUSION
The present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.
PubMed: 36578296
DOI: 10.3389/fpsyt.2022.1070522 -
The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
Expert Review of Clinical Pharmacology Dec 2022To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of topical difamilast in the treatment of patients with atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD).
METHODS
Only randomized controlled trials (RCTs) that compared topical difamilast with vehicle treatment for patients with AD were included. PubMed, Web of Science, Ovid Medline, Cochrane Library, ClinicalTrials.gov and JapicCTI were searched to 10 April 2022.
RESULTS
Five studies enrolling a total of 1009 patients with mild-to-moderate AD were identified. Compared with the topical vehicle, topical difamilast was associated with a significantly higher success rate according to the Investigator's Global Assessment score at week 4 (relative risk, 2.82; 95% confidence interval [CI]: 2.11-3.77). Compared with the vehicle, difamilast was associated with a significant decrease in day 28 eczema area and severity index scores (mean difference [MD], -4.10; 95% CI: -5.32 to -2.87), verbal rating scale scores (MD, -0.51; 95% CI: -0.71 to -0.32), visual analog scale scores (MD, -12.15; 95% CI: -19.70 to -4.61), patient-oriented eczema measure values (MD, -3.99; 95% CI: -4.91 to -3.07), and total affected body surface area (MD, -6.48; 95% CI: -8.09 to -4.87). No difference in treatment-related adverse events was identified.
CONCLUSIONS
This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.
Topics: Humans; Dermatitis, Atopic; Randomized Controlled Trials as Topic; Treatment Outcome; Eczema; Double-Blind Method; Severity of Illness Index
PubMed: 36210241
DOI: 10.1080/17512433.2022.2134114 -
Pharmaceutical Nanotechnology 2023Delivery systems with low immunogenicity and toxicity are believed to enhance the efficacy of specific targeted drug delivery to cancer cells. Exosomes are potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delivery systems with low immunogenicity and toxicity are believed to enhance the efficacy of specific targeted drug delivery to cancer cells. Exosomes are potential natural nanosystems that can enhance the delivery of therapeutic agents for targeted cancer therapy.
OBJECTIVE
This study provides a precise effect size of exosomes as nanovesicles for in vitro delivery of anticancer agents.
METHODS
In this systematic review and meta-analysis, the efficacy of exosomes as nanocarriers for the delivery of therapeutic molecules was investigated using the random-effects model. We did comprehensive literature searches through CINAHL, Cochrane, PubMed, Scopus, and Science Direct of in vitro studies that reported exosomes as delivery systems for cancer therapy.
RESULTS
After the screening of eligible articles, a total of 50 studies were enrolled for the metaanalysis. The results showed that cancer cells treated with exosome-loaded anticancer agents for at least 6 h significantly decreased cell viability and increased cytotoxicity with the standardized mean difference (SMD) of -1.47 (-2.18, -0.76; (p<0.0001) and -1.66 (-2.71, -0.61; p<0.002). Exosomes effectively delivered drugs and exogenous miRNAs, siRNAs, viruses, and enzymes to cancer cells in vitro.
CONCLUSION
This meta-analysis provides evidence of exosomes as efficient nanocarriers for the delivery of anticancer drugs.
Topics: Humans; Exosomes; Neoplasms; Antineoplastic Agents; Drug Delivery Systems; RNA, Small Interfering
PubMed: 36200247
DOI: 10.2174/2211738510666220930155253 -
American Journal of Preventive Medicine Dec 2022There is substantial debate concerning the impact of cannabis decriminalization and legalization on road safety outcomes. (Review)
Review
INTRODUCTION
There is substantial debate concerning the impact of cannabis decriminalization and legalization on road safety outcomes.
METHODS
Seven databases were systematically searched: Embase, MEDLINE, and PsycINFO through Ovid as well as Web of Science Core Collection, SafetyLit, Criminal Justice Database (ProQuest), and Transport Research International Documentation (from inception to June 16, 2021). Eligible primary studies examined group-level cannabis decriminalization or legalization and a road safety outcome in any population.
RESULTS
A total of 65 reports of 64 observational studies were eligible, including 39 that applied a quasi-experimental design. Studies examined recreational cannabis legalization (n=50), medical cannabis legalization (n=22), and cannabis decriminalization (n=5). All studies except 1 used data from the U.S. or Canada. Studies found mixed impacts of legalization on attitudes, beliefs, and self-reported driving under the influence. Medical legalization, recreational legalization, and decriminalization were associated with increases in positive cannabis tests among drivers. Few studies examined impacts on alcohol or other drug use, although findings suggested a decrease in positive alcohol tests among drivers associated with medical legalization. Medical legalization was associated with reductions in fatal motor-vehicle collisions, whereas recreational legalization was conversely associated with increases in fatal collisions.
DISCUSSION
Increased cannabis positivity may reflect changes in cannabis use; however, it does not in itself indicate increased impaired driving. Subgroups impacted by medical and recreational legalization, respectively, likely explain opposing findings for fatal collisions. More research is needed concerning cannabis decriminalization; the impacts of decriminalization and legalization on nonfatal injuries, alcohol and other drugs; and the mechanisms by which legalization impacts road safety outcomes.
Topics: Humans; Cannabis; Marijuana Smoking; Legislation, Drug; Substance-Related Disorders; Accidents, Traffic
PubMed: 36167602
DOI: 10.1016/j.amepre.2022.07.012