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Journal of Controlled Release :... Nov 2023Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an...
Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).
Topics: Humans; Administration, Intranasal; Hydrogels; Silicon; Porosity; Mometasone Furoate; Inflammation
PubMed: 37769816
DOI: 10.1016/j.jconrel.2023.09.045 -
Acta Biochimica Polonica Sep 2023This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients with moderate and severe AR treated at our hospital between January 2017 and August 2020 were recruited as subjects for this study. The patients were randomly divided into control and experimental groups, with 70 patients in each group. Mometasone nasal spray was used in both groups, and vitamin D was administered to the experimental group for four weeks. The total nasal symptom scores (TNSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to assess the efficacy of treatment. T lymphocyte subsets (CD3+, CD4+ and CD8+) and serum anti-inflammatory and proinflammatory cytokines such as interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were analyzed. The incidence of adverse reactions was recorded. Serum vitamin D levels were lower in patients with AR. After 4 weeks of treatment, total TNSS scores, T lymphocyte subsets (CD3+, CD4+), CD4+/CD8+ ratio, TNF-α, and total RQLQ scores were significantly reduced compared to the initial testing (P<0.05) in the two groups; CD8+, IFN-γ, and IL-10 levels as well as serum vitamin D were significantly increased compared to the initial test (P<0.05). The improvement in these parameters in the experimental group was significantly greater than that in the control group (P<0.05), except for sneezing and eye symptoms in the TNSS and RQLQ scores. It was concluded that vitamin D supplementation improves the therapeutic effect of mometasone nasal spray on AR and is thus recommended as an adjuvant therapy for moderate and severe AR.
Topics: Humans; Mometasone Furoate; Interleukin-10; Nasal Sprays; Quality of Life; Tumor Necrosis Factor-alpha; Rhinitis, Allergic; Vitamins; Vitamin D; Interferon-gamma; Dietary Supplements
PubMed: 37716008
DOI: 10.18388/abp.2020_6637 -
Clinical Drug Investigation Sep 2023Indacaterol acetate (IND), a long-acting β-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Indacaterol acetate (IND), a long-acting β-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma.
METHODS
In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥ 6 to < 12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV) after two weeks of treatment.
RESULTS
In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 μg group and 25% patients in IND 150 μg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥ 0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile.
CONCLUSIONS
Once-daily IND 75 μg and IND 150 μg via Breezhaler in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 μg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT02892019; 08-Sep-2016).
Topics: Humans; Child; Asthma; Double-Blind Method; Forced Expiratory Volume; Acetates
PubMed: 37682405
DOI: 10.1007/s40261-023-01300-8 -
International Medical Case Reports... 2023Acne necrotica is a rare disease, characterized by recurrent crops of inflammatory papules and papulo-pustules that rapidly become necrotic, leaving varioliform scars of...
Acne necrotica is a rare disease, characterized by recurrent crops of inflammatory papules and papulo-pustules that rapidly become necrotic, leaving varioliform scars of varying extent. Here, I report the case of a 32-year-old male with early-stage disease and a 58-year-old male with late-stage acne necrotica. Both patients had a history of chronic, relapsing, umbilicated, and centrally necrotic erythematous papules and papulo-pustules involving the hairline and face. A diagnosis of acne necrotica was made based on the clinical presentation, and both patients started on topical mometasone furoate cream and doxycycline tablets and responded well. Herein I report this case to reappraise an under-recognized entity of acne necrotica.
PubMed: 37636990
DOI: 10.2147/IMCRJ.S421796 -
Skin Health and Disease Aug 2023There was a lack of high-quality, evidence-based treatment for lichen simplex chronicus (LSC). Topical steroid under hydrocolloid dressing treatment was investigated...
There was a lack of high-quality, evidence-based treatment for lichen simplex chronicus (LSC). Topical steroid under hydrocolloid dressing treatment was investigated mostly in observational studies without investigation of the cost-effectiveness and the methodology of application also varied without standardisation. To investigate the cost-effectiveness of topical steroid under hydrocolloid dressing in the treatment of moderate to severe lichen simplex chronicus (LSC). The study aimed to provide a clear methodology that was replicable. A single-blinded randomized controlled trial was carried out to compare the efficacy of 0.1% mometasone furoate cream with or without hydrocolloid dressing in patients suffering from moderate to severe LSC. Physician Global Assessment (PGA) score, Eczema Area and Severity Index (EASI) individual components score were assessed by a Dermatologist through clinical photos at week 0, 2, and 4. Pruritis Numerical Rating Scale (PNRS) was rated. Forty adult patients were recruited. The group with hydrocolloid dressing showed superior treatment efficacy. 20 out of 20 patients benefited from the hydrocolloid dressing with topical steroid while only 6 out of 20 patients benefited from topical steroid alone at week 2 regarding PGA. Similar result was obtained at week 4. Extra HK$ 132 was needed for each patient in hydrocolloid with topical steroid group. The number needed to treat (NNT) was 1.43 (95% CI: 1.42-1.44) at week 2 and 1.42 (95% CI: 1.41-1.44) at week 4 regarding PGA score improvement of ≥2. NNT analysis supported the cost-effectiveness of adjunctive hydrocolloid dressing usage as the first-line treatment in patients with moderate to severe LSC. This study added evidence to LSC treatment with a detailed and reproducible methodology.
PubMed: 37538322
DOI: 10.1002/ski2.228 -
PloS One 2023The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from...
Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.
BACKGROUND
The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed.
RESULTS
Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration.
CONCLUSION
Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.
Topics: Humans; Nasal Sprays; Anosmia; Quality of Life; Triamcinolone Acetonide; COVID-19; Randomized Controlled Trials as Topic; Steroids; Adrenal Cortex Hormones; Fluticasone
PubMed: 37531338
DOI: 10.1371/journal.pone.0288285 -
EClinicalMedicine Jul 2023Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin...
Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.
BACKGROUND
Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP.
METHODS
A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398.
FINDINGS
Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related.
INTERPRETATION
These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP.
FUNDING
KeyMed Biosciences (Chengdu) Limited.
PubMed: 37483544
DOI: 10.1016/j.eclinm.2023.102076 -
Respiratory Medicine Oct 2023Baseline characteristics could potentially guide asthma treatments. We evaluated whether baseline eosinophil levels affect the efficacy of...
Efficacy of mometasone/indacaterol/glycopyrronium in patients with inadequately controlled asthma with respect to baseline eosinophil count: Post hoc analysis of IRIDIUM study.
BACKGROUND
Baseline characteristics could potentially guide asthma treatments. We evaluated whether baseline eosinophil levels affect the efficacy of mometasone/indacaterol/glycopyrronium (MF/IND/GLY) in patients with inadequately controlled asthma.
METHOD
In this post hoc analysis of IRIDIUM study, efficacy of high-dose MF/IND/GLY (160/150/50 μg, once-daily [o.d.]) versus high-dose MF/IND (320/150 μg o.d.) and high-dose fluticasone/salmeterol (FLU/SAL [500/50 μg, twice-daily [b.i.d.]); and efficacy of pooled MF/IND/GLY (160/150/50 μg and 80/150/50 μg) versus pooled MF/IND (320/150 μg and 160/150 μg) was evaluated in patient subgroups with baseline blood eosinophil count of <300 cells/μL or ≥300 cells/μL.
RESULTS
Overall, 3065 patients were included. At Week 26, high-dose MF/IND/GLY showed improved trough FEV versus high-dose MF/IND (Δ78mL [<300 cells/μL]; Δ54mL [≥300 cells/μL]) and FLU/SAL (Δ112mL [<300 cells/μL]; Δ98mL [≥300 cells/μL]). Similarly, pooled MF/IND/GLY also showed improved trough FEV versus pooled MF/IND (Δ75mL [<300 cells/μL]; Δ68mL [≥300 cells/μL]). Over 52 weeks, high-dose MF/IND/GLY reduced the annualized rate of moderate or severe asthma exacerbations by 23% and 10%, severe exacerbations by 31% and 15%, and all exacerbation by 33% and 10% versus high-dose MF/IND for subgroups with <300 cells/μL and ≥300 cells/μL, respectively; and by 33% and 41%, 45% and 42%, 42% and 39% versus FLU/SAL, respectively. Similarly, pooled MF/IND/GLY reduced exacerbations by 22% and 8%, 21% and 7%, 27% and 8%, versus pooled MF/IND, for the respective subgroups.
CONCLUSION
MF/IND/GLY showed improvement in lung function and reduction in asthma exacerbations over MF/IND and FLU/SAL independent of baseline eosinophil levels, indicating that eosinophil levels did not affect the efficacy of MF/IND/GLY in patients with inadequately controlled asthma.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02571777 (IRIDIUM).
PubMed: 37392789
DOI: 10.1016/j.rmed.2023.107334 -
World Journal of Clinical Cases Jun 2023Purpura annularis telangiectodes of Majocchi (PATM), also known as Majocchi, is a rare subclass of pigmented purpuric dermatoses. The etiology of PATM is unknown, but it...
BACKGROUND
Purpura annularis telangiectodes of Majocchi (PATM), also known as Majocchi, is a rare subclass of pigmented purpuric dermatoses. The etiology of PATM is unknown, but it seems more common in children and young women. The skin lesions are mostly symmetrical ring-shaped reddish-brown macules on the lower limbs.
CASE SUMMARY
A 9-year-old girl, who has received treated in our department, presented with reddish-brown ring-shaped rash on both lower limbs that had been present for 6 mo. These lesions, red brownish annular or petaloid patches, were mostly found on ankles and lower limber, which do not fade when adding pressure and no feel of infiltration and no atrophy when touching those lesions. Pathological examination showed deposition of hemosiderin in papillary dermis. However, dermoscopy showed the pigmentation in the center as well as the lavender patches on the edge of lesion. The child was thus diagnosed with PATM. After diagnosis, we suggested the patient avoid strenuous exercise. she was given vitamin C tablets for oral and mometasone furoate cream for external use. Follow-up examinations and treatment continue to support the clinical diagnosis to date.
CONCLUSION
This is the first report of investigating PATM using dermoscopy, which can differentiate PATM from other diseases due to its unique microscopic feature under dermoscopy. Although PATM is harmless, it still requires long-term follow-up. Moreover, dermoscopy technique can be applied for observation of multi-site lesions and correlated with histopathology. Thus, we believe this approach could be generalized for future diagnosis of PATM.
PubMed: 37383137
DOI: 10.12998/wjcc.v11.i16.3858 -
Frontiers in Pharmacology 2023No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis... (Review)
Review
Comparative efficacy and acceptability of licensed dose intranasal corticosteroids for moderate-to-severe allergic rhinitis: a systematic review and network meta-analysis.
No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis assessed the comparative efficacy and acceptability of licensed dose aqueous INCSs. PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until 31 March 2022. Eligible studies included randomized controlled trials comparing INCSs with placebo or other types of INCSs in patients with moderate-to-severe allergic rhinitis. Two reviewers independently screened and extracted data following the Preferred Reporting Items in Systematic Reviews and Meta-analysis guideline. A random-effects model was used for data pooling. Continuous outcomes were expressed as standardized mean difference (SMD). The primary outcomes were the efficacy in improving total nasal symptom score (TNSS) and treatment acceptability (the study dropout). We included 26 studies, 13 with 5,134 seasonal AR patients and 13 with 4,393 perennial AR patients. Most placebo-controlled studies had a moderate quality of evidence. In seasonal AR, mometasone furoate (MF) was ranked the highest efficacy, followed by fluticasone furoate (FF), ciclesonide (CIC), fluticasone propionate and triamcinolone acetonide (TAA) (SMD -0.47, 95% CI: -0.63 to -0.31; -0.46, 95% CI: -0.59 to -0.33; -0.44, 95% CI: -0.75 to -0.13; -0.42, 95% CI: -0.67 to -0.17 and -0.41, 95% CI: -0.81 to -0.00), In perennial AR, budesonide was ranked the highest efficacy, followed by FF, TAA, CIC, and MF (SMD -0.43, 95% CI: -0.75 to -0.11; -0.36, 95% CI: -0.53 to -0.19; -0.32, 95% CI: -0.54 to -0.10; -0.29, 95% CI: -0.48 to -0.11; and -0.28, 95% CI: -0.55 to -0.01). The acceptability of all included INCSs was not inferior to the placebo. According to our indirect comparison, some INCSs have superior efficacy to others with moderate quality of evidence in most placebo-controlled studies for treating moderate-to-severe AR.
PubMed: 37288109
DOI: 10.3389/fphar.2023.1184552