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International Journal of Chronic... 2024Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal.
METHODS
Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken.
RESULTS
Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants).
DISCUSSION
Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Administration, Inhalation; Lung; Adrenal Cortex Hormones; Disease Progression; Forced Expiratory Volume; Treatment Outcome; Bronchodilator Agents; Randomized Controlled Trials as Topic; Observational Studies as Topic; Time Factors; Aged; Drug Administration Schedule; Risk Factors; Middle Aged; Female; Male
PubMed: 38919905
DOI: 10.2147/COPD.S436525 -
Acta Dermatovenerologica Alpina,... Jun 2024Melasma, a chronic acquired skin pigmentation disorder, is characterized by the presence of irregular-edged brown to gray-brown patches with a symmetrical distribution,... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The effectiveness and safety of 3% tranexamic acid cream vs. 4% hydroquinone cream for mixed-type melasma in skin of color: a double-blind, split-face, randomized controlled trial.
INTRODUCTION
Melasma, a chronic acquired skin pigmentation disorder, is characterized by the presence of irregular-edged brown to gray-brown patches with a symmetrical distribution, primarily on sun-exposed areas such as the face. Topical hydroquinone (HQ) is the gold standard for melasma treatment but has numerous side effects. This study assesses the effectiveness of topical tranexamic acid (TA) as an alternative for melasma treatment.
METHODS
In a double-blind, split-face, randomized controlled trial involving 20 subjects, the effectiveness of 3% TA versus 4% HQ cream was evaluated over 8 weeks. The modified melasma area and severity index (mMASI), melanin index, erythema index, and side effects were assessed. Subjective improvement was measured using the patient global assessment (PtGA).
RESULTS
A significant decline in the mMASI score was observed at weeks 4 and 8 in both groups compared to baseline. There were no statistically significant differences in PtGA scores between the 3% TA group and the 4% HQ group.
CONCLUSIONS
Topical 3% TA is as effective and safe as 4% HQ for treating melasma in the Indonesian population, with potential advantages in terms of side-effect profiles.
Topics: Humans; Melanosis; Double-Blind Method; Hydroquinones; Tranexamic Acid; Female; Adult; Middle Aged; Treatment Outcome; Male; Skin Cream; Skin Pigmentation; Administration, Cutaneous; Severity of Illness Index
PubMed: 38918942
DOI: No ID Found -
Asian Pacific Journal of Cancer... Jun 2024Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A Randomized Single-Blinded Phase II Trial Comparing Efficacy and Quality of Life of Topical Aloe Vera Gel Plus Urea Cream Versus Urea Cream Alone for Prevention of Hand Foot Syndrome in Cancer Patients Receiving Capecitabine.
INTRODUCTION
Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination.
MATERIALS AND METHODS
The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively.
RESULTS
Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group.
CONCLUSION
Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.
Topics: Humans; Capecitabine; Female; Male; Middle Aged; Quality of Life; Hand-Foot Syndrome; Urea; Antimetabolites, Antineoplastic; Single-Blind Method; Plant Preparations; Prognosis; Follow-Up Studies; Adult; Administration, Topical; Aged; Neoplasms; Skin Cream; Aloe
PubMed: 38918684
DOI: 10.31557/APJCP.2024.25.6.2203 -
Scientific Reports Jun 2024Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are... (Randomized Controlled Trial)
Randomized Controlled Trial
Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.
Topics: Humans; Vitiligo; Atorvastatin; Simvastatin; Male; Female; Double-Blind Method; Adult; Pilot Projects; Middle Aged; Administration, Topical; Young Adult; Treatment Outcome; Adolescent
PubMed: 38918590
DOI: 10.1038/s41598-024-65722-w -
Scientific Reports Jun 2024In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable....
In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable. From the national health insurance claims data in South Korea, we included 425 new users of OAC among patients with non-valvular AF and ESRD undergoing dialysis between 2013 and 2020. Patients were categorized into DOAC (n = 106) and warfarin group (n = 319). Clinical outcomes, including ischemic stroke, myocardial infarction (MI), intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding, were compared between the two groups using inverse probability of treatment weighting (IPTW) analysis. During the median follow-up of 3.2 years, the incidence of ischemic stroke was significantly reduced in the DOAC compared to the warfarin group [Hazard ratio (HR) 0.07; P = 0.001]. However, the incidence of MI (HR 1.32; P = 0.41) and GI bleeding (HR 1.78; P = 0.06) were not significantly different between the two groups. No ICH events occurred in the DOAC group, although the incidence rate did not differ significantly between the two groups (P = 0.17). In Asian patients with AF and ESRD undergoing dialysis, DOACs may be associated with a reduced risk of ischemic stroke compared with warfarin. The MI, ICH, and GI bleeding rates may be comparable between DOACs and warfarin.
Topics: Humans; Atrial Fibrillation; Kidney Failure, Chronic; Male; Female; Renal Dialysis; Aged; Anticoagulants; Warfarin; Administration, Oral; Middle Aged; Republic of Korea; Incidence; Asian People; Gastrointestinal Hemorrhage; Myocardial Infarction; Ischemic Stroke; Aged, 80 and over
PubMed: 38918543
DOI: 10.1038/s41598-024-65541-z -
Scientific Reports Jun 2024Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a...
Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.
Topics: Mesenchymal Stem Cells; Osteogenesis; Humans; Hydrogels; Cell Differentiation; Porosity; Alkaline Phosphatase; Cells, Cultured; Cell Encapsulation; Mesenchymal Stem Cell Transplantation; Injections
PubMed: 38918510
DOI: 10.1038/s41598-024-65731-9 -
AAPS PharmSciTech Jun 2024The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after...
The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.
Topics: Nanoparticles; Animals; Antioxidants; Rats; Polymers; Anti-Inflammatory Agents; Lipids; Drug Carriers; Abietanes; X-Ray Diffraction; Drug Liberation; Administration, Oral; Male; Particle Size; Rats, Wistar; Chemistry, Pharmaceutical
PubMed: 38918292
DOI: 10.1208/s12249-024-02860-4 -
AAPS PharmSciTech Jun 2024The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances...
The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.
Topics: Micelles; Dexamethasone; Chitosan; Gels; Drug Delivery Systems; Poloxamer; Drug Liberation; Surface-Active Agents; Chemistry, Pharmaceutical; Hydrogels; Anti-Inflammatory Agents; Nanoparticles; Drug Carriers; Rheology; Oral Ulcer; Administration, Oral; Lipids; Oleic Acid
PubMed: 38918282
DOI: 10.1208/s12249-024-02862-2 -
Nicotine & Tobacco Research : Official... Jun 2024Pictorial health warning labels (HWLs) can communicate the harms of tobacco product use, yet little research exists for cigars. We sought to identify the most effective...
INTRODUCTION
Pictorial health warning labels (HWLs) can communicate the harms of tobacco product use, yet little research exists for cigars. We sought to identify the most effective types of images to pair with newly developed cigar HWLs.
AIMS AND METHODS
In September 2021, we conducted an online survey experiment with US adults who reported using little cigars, cigarillos, or large cigars in the past 30 days (n = 753). After developing nine statements about health effects of cigar use, we randomized participants to view one of three levels of harm visibility paired with each statement, either: (1) an image depicting internal harm not visible outside the body, (2) an image depicting external harm visible outside of the body, or (3) two images depicting both internal and external harm. After viewing each image, participants answered questions on perceived message effectiveness (PME), negative affect, and visual-verbal redundancy (VVR). We used linear mixed models to examine the effect of harm visibility on each outcome, controlling for warning statement.
RESULTS
Warnings with both and external harm depictions performed significantly better than the internal harm depictions across all outcomes, including PME (B = 0.21 and B = 0.17), negative affect (B = 0.26 and B = 0.25), and VVR (B = 0.24 and B = 0.17), respectively (all p < .001). Compared to both, the external depiction of harm did not significantly change PME or negative affect but did significantly lower VVR (B = -0.07, p = .01).
CONCLUSIONS
Future cigar pictorial HWLs may benefit from including images depicting both or external harm depictions. Future research should examine harm visibility's effect for other tobacco pictorial HWLs.
IMPLICATIONS
The cigar health warning labels (HWLs) proposed by the US Food and Drug Administration are text-only. We conducted an online survey experiment among people who use cigars to examine the effectiveness of warnings with images depicting different levels of harm visibility. We found HWLs with images depicting both an internal and external depiction of cigar harm, or an external depiction of harm alone, performed better overall than images portraying internal depictions of harm. These findings provide important regulatory evidence regarding what type of images may increase warning effectiveness and offer a promising route for future cigar HWL development.
PubMed: 38918001
DOI: 10.1093/ntr/ntae113 -
Med (New York, N.Y.) Jun 2024Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a...
BACKGROUND
Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration.
METHODS
Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored.
FINDINGS
Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy.
CONCLUSIONS
Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation.
FUNDING
This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.
PubMed: 38917792
DOI: 10.1016/j.medj.2024.05.017