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Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006 -
Cureus Oct 2021Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but... (Review)
Review
Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but long-standing clinical challenge. We aimed to approximate the risk of clinical acute liver injury among users of oral antifungals in the general population. This review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six articles were included, comprising case reports and cohort studies, after eliminating duplicate publications. No randomized control studies were found. In all studies, the duration of antifungal use was associated with significantly increased liver enzyme levels. Although it is not very common for patients on antifungals to develop acute liver failure, the prognosis is often good with swift discontinuation of the drug and proper treatment. Liver function evaluation before treatment and periodic monitoring every three to six weeks after commencement of treatment is suggested.
PubMed: 34703680
DOI: 10.7759/cureus.18940 -
The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Frontiers in Cellular and Infection... 2022Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a... (Review)
Review
PURPOSE
Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD.
METHODS
We performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review.
RESULTS
IFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD.
CONCLUSION
Taken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions.
Topics: Humans; Triazoles; Invasive Fungal Infections; Nitriles; Antifungal Agents; Aspergillosis; Mucormycosis; Candidiasis, Invasive
PubMed: 36530445
DOI: 10.3389/fcimb.2022.1049959 -
Indian Journal of Dermatology 2023is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics,... (Review)
Review
is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics, immunosuppressant agents, and other immunocompromising conditions. Currently, bLf and antifungal drugs have been known to have synergistic effects, increasing the drug's efficacy. This study aims to investigate the efficacy of the synergistic effect of bLf and antifungal drugs. This review addressed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We conducted literature searches to assess the association of lactoferrin and current antifungal therapy against in ProQuest, PubMed, MEDLINE, EBSCOhost, SAGE, JSTOR, GARUDA, and Open Gray with no date restriction (until March 5, 2021). We used Jeffry's Amazing Statistical Program (JASP) to measure the overall size effect of MIC (minimum inhibitory concentration) between studies. A total of 7 studies retained were experimental in vitro studies. Based on the available data, 4 out of 7 studies were included in the quantitative analysis. This systematic review showed that bovine lactoferrin could help inhibit the development of azole-susceptible and azole-resistant . Furthermore, there was synergistic activity between lactoferrin and various antifungals. Our meta-analysis showed that lactoferrin could significantly inhibit the growth than the control group. Bovine lactoferrin and its peptide derivatives isolated from bovine milk can significantly inhibit the growth of , both susceptible to azoles and those with azole resistance.
PubMed: 38371540
DOI: 10.4103/ijd.ijd_275_22 -
American Journal of Transplantation :... Dec 2014Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A... (Meta-Analysis)
Meta-Analysis Review
Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A comprehensive literature search was performed to identify randomized controlled trials comparing regimens for antifungal prophylaxis in liver transplant recipients. Direct comparisons were made between treatments using random-effects meta-analysis and a Bayesian network meta-analysis was performed for the primary end point of proven IFI. Fourteen studies met inclusion criteria, reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB), itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause mortality was not significantly affected. There was no difference in risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB reduces the incidence of IFI following liver transplantation, and the available evidence suggests that the two are equivalent in efficacy.
Topics: Antibiotic Prophylaxis; Antifungal Agents; Graft Rejection; Humans; Liver Diseases; Liver Transplantation; Mycoses; Postoperative Complications
PubMed: 25395336
DOI: 10.1111/ajt.12925 -
Exploration of Targeted Anti-tumor... 2023One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as... (Review)
Review
AIM
One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as up to 50% of authorized drugs in the last 30 years have been isolated from natural sources.
METHODS
Anticancer, antioxidant, antibacterial, antifungal, antiviral, analgesic, anti-inflammatory, and other actions have all been reported in research papers using plants from the genus in the treatment and prevention of disease.
RESULTS
Results from the anticancer test showed that the genus, especially , and had significant promise as an anticancer agent against several cancer cell lines. Numerous factors, including phytochemical composition, increased apoptotic activity, decreased cell proliferation, stopped angiogenesis, and reduced inflammation.
CONCLUSIONS
These results, despite preliminary, show promise for further purification and investigation of bioactive compounds and extracts within the genus for their anticancer properties.
PubMed: 37205310
DOI: 10.37349/etat.2023.00134 -
Mycopathologia Oct 2021Fungal infection and sensitization are common in chronic respiratory patient populations such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic... (Review)
Review
INTRODUCTION
Fungal infection and sensitization are common in chronic respiratory patient populations such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) and are often associated with prolonged antifungal therapy (Hohmann et al. in Clin Infect Dis 15:939-940, 2010; Vissichelli et al. in Infect Prev Pract 1:100029, 2019), morbidity, and mortality. Although the use of antifungal stewardship (AFS) is increasing within an invasive fungal disease setting, its use and impact within a chronic respiratory setting have not been defined.
METHODS
A systematic literature review was conducted using PRISMA guidelines to evaluate the use of antifungal stewardship within a chronic respiratory care setting. Three databases have been searched, Medline via Ovid, Embase and GlobalHealth, for papers published between 1949 and 2020.
RESULTS
The initial search identified 987 papers from Medline, 1761 papers from Embase, and 481 papers from GlobalHealth. Only 28 papers met the criteria for inclusion in this systematic literature review. The included studies were subjected to CASP and GRADE assessments to rank their quality and applicability. Only two studies were focussed on Aspergillus species infection.
CONCLUSION
Although antifungal stewardship is increasing, its applications are still limited in chronic respiratory care settings despite the prolonged requirement for antifungal therapy and high antimicrobial resistance.
Topics: Antifungal Agents; Bronchiectasis; Humans; Invasive Fungal Infections; Mycoses; Patient Acceptance of Health Care
PubMed: 33991279
DOI: 10.1007/s11046-021-00547-z -
Journal of Evidence-based Integrative... 2022infections have increased significantly in the antimicrobial resistance era, and synthetic antifungal drugs have limitations. The present work aimed to review the... (Review)
Review
BACKGROUND AND PURPOSE
infections have increased significantly in the antimicrobial resistance era, and synthetic antifungal drugs have limitations. The present work aimed to review the antifungal properties of () as an herbal remedy.
METHOD
PubMed, Scopus, ScienceDirect, Web of Science, SID, Civilica, and Magiran databases were searched for the antifungal activity on , , dental biofilm, and clinical studies of on species.
RESULTS
Overall, 33 articles evaluated the effect of on species and classified them into four groups, as follows in vitro (23), dental biofilm (6), in vivo (2), and clinical studies (3). All studies considered effective in reducing or even inhibiting the growth of species. NoMFC significant differences were seen in the effect of on susceptible compared to the resistant groups of in the studies. It was also influential in inhibiting and .
CONCLUSION
Considering the side effects and resistance of current antifungal drugs as well as the benefits of using herbal medicines, such as lower cost, less likely to develop drug resistance, the absence of side effects, and toxicity compared with chemical ones it is possible as a powerful alternative to replace or combine with the current antifungal for infection therapy along with other therapies.
Topics: Candida; Antifungal Agents; Drug Resistance, Fungal; Candidiasis; Lamiaceae; Candida glabrata
PubMed: 36423242
DOI: 10.1177/2515690X221132272 -
European Archives of... Aug 2023This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on... (Review)
Review
PURPOSE
This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.
METHODS
Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments.
RESULTS
Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL.
CONCLUSION
Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.
Topics: Humans; Child; Sirolimus; Prospective Studies; Treatment Outcome; Neck; Head; Lymphatic Abnormalities; Vascular Malformations
PubMed: 37115326
DOI: 10.1007/s00405-023-07991-1