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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 -
Journal of Lasers in Medical Sciences 2023The immune response to laser tattoo removal poses a significant challenge in its management, primarily due to its unpredictable nature, which can range from mild... (Review)
Review
The immune response to laser tattoo removal poses a significant challenge in its management, primarily due to its unpredictable nature, which can range from mild hypersensitivity reactions to severe anaphylaxis. Such responses can potentially hinder the effectiveness of laser tattoo removal procedures. Therefore, gaining a comprehensive understanding of the immune response to tattoo removal using laser techniques is of utmost importance to develop more efficient management strategies. This study aims to address this need by analyzing eight carefully selected articles obtained through a thorough literature review. To explore the immune response associated with laser techniques in tattoo removal, we employed a rigorous research methodology. A thorough literature review was conducted using reputable search engines such as Google Scholar, SagePub, and PubMed to collect relevant articles. Initially, 788 potential articles were identified through this process. Following meticulous scrutiny, only eight articles that met stringent inclusion criteria were selected for our study. This meticulous selection process ensures that the information presented here is derived from high-quality and pertinent research. Based on the analysis of the eight selected articles, our findings illuminate the various immune responses that emerge following tattoo removal using laser techniques. These responses include hypersensitivity reactions, allergic manifestations, and, in certain instances, anaphylaxis. Hypersensitivity reactions typically manifested as erythema, edema, and pruritus, while allergic responses were observed in the form of urticaria. In summary, our study highlights that the immune response to laser tattoo removal primarily elicits hypersensitivity and, in some cases, anaphylaxis reactions. Our study underscores the significance of clinicians being vigilant regarding potential immune responses during laser tattoo removal. It is crucial to closely monitor patients to promptly address any adverse reactions. Further research holds the potential to enhance our understanding, paving the way for improved management strategies that can enhance patient safety and treatment success.
PubMed: 38318216
DOI: 10.34172/jlms.2023.66 -
Postepy Dermatologii I Alergologii Dec 2023Upadacitinib, an oral selective-JAK1 inhibitor, has been used in clinical trials to treat atopic dermatitis (AD). (Review)
Review
INTRODUCTION
Upadacitinib, an oral selective-JAK1 inhibitor, has been used in clinical trials to treat atopic dermatitis (AD).
AIM
To evaluate the efficacy and safety of upadacitinib in moderate-to-severe AD.
MATERIAL AND METHODS
We searched clinical trials from PubMed, Embase, Cochrane Library databases, and Web of Science. All randomized controlled trials (RCTs) of upadacitinib treatment on patients with moderate-to-severe AD were included. A meta-analysis was performed using the fixed- or random-effects models to calculate pooled standard mean differences or relative risks (SMD or RR, respectively).
RESULTS
Compared with the placebo group, our meta-analysis revealed that upadacitinib was related to a significant decrease in Eczema Area and Severity Index (EASI) scores, and pruritus numeric rating scale (NRS) scores. A higher response rate in Investigator's Global Assessment (IGA) and EASI-75 were also detected in the upadacitinib group. Although patients treated with upadacitinib experienced a higher incidence of adverse events (AEs), these AEs were mild and tolerated. As for serious adverse events (SAEs), there was no difference between the placebo group and the upadacitinib group.
CONCLUSIONS
This meta-analysis demonstrated that upadacitinib is a safe and effective treatment for moderate-to-severe AD. Further long-term trials are required for confirmation.
PubMed: 38282878
DOI: 10.5114/ada.2023.133820 -
Healthcare (Basel, Switzerland) Jan 2024Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes.... (Review)
Review
Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes. Currently, there is no cure for any of the EB subtypes associated with various mutations. Existing therapies primarily focus on alleviating pain and promoting early wound healing to prevent potential complications. Consequently, there is an urgent need for innovative therapeutic approaches. The objective of this research was to assess the efficacy of various topical treatments in patients with EB with the goal of achieving wound healing. A secondary objective was to analyse the efficacy of topical treatments for symptom reduction. A literature search was conducted using scientific databases, including The Cochrane Library, Medline (Pubmed), Web of Science, CINHAL, Embase, and Scopus. The protocol review was registered in PROSPERO (ID: 418790), and inclusion and exclusion criteria were applied, resulting in the selection of 23 articles. Enhanced healing times were observed compared with the control group. No conclusive data have been observed on pain management, infection, pruritus episodes, and cure rates over time. Additionally, evidence indicates significant progress in gene therapies (B-VEC), as well as cell and protein therapies. The dressing group, Oleogel S-10, allantoin and diacerein 1%, were the most represented, followed by fibroblast utilisation. In addition, emerging treatments that improve the patient's innate immunity, such as calcipotriol, are gaining attention. However, more trials are needed to reduce the prevalence of blistering and improve the quality of life of individuals with epidermolysis bullosa.
PubMed: 38275540
DOI: 10.3390/healthcare12020261 -
Journal of Clinical Medicine Jan 2024This study aimed to investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) in postoperative acute pain control. PubMed, Scopus, and... (Review)
Review
This study aimed to investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) in postoperative acute pain control. PubMed, Scopus, and Cochrane Library were searched on 1-8 December 2022, for randomized controlled trials on the analgesic effects of TENS. The outcomes were pain intensity and opioid use (primary), and postoperative (PO) adverse events, blood pressure, and the duration of hospital stay (secondary); PROSPERO CRD42022333335. A total of 40 articles were included in the meta-analysis. Pain intensity at rest and during coughing for all types of surgeries combined was lower in the TENS group (standardized mean difference (SMD) = -0.51 [-0.61, -0.41], < 0.00001, 29 studies, and -1.28 [-2.46, -0.09], -value = 0.03, six studies, respectively). There was a statistically significant decrease in morphine requirements, as well as in the incidence of postoperative nausea and vomiting, dizziness, and pruritus. There was no difference between the groups in postoperative pain intensity during walking, in blood pressure, and only a borderline difference in the length of hospital stay. The subgroup analysis by surgery type did not show significant differences between the groups in pain severity at rest. Thus, TENS has a potential for pain control and postoperative recovery outcomes.
PubMed: 38256561
DOI: 10.3390/jcm13020427 -
Life (Basel, Switzerland) Jan 2024Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, usually presented in the third trimester with pruritus, elevated... (Review)
Review
Severe Early-Onset Intrahepatic Cholestasis of Pregnancy Following Ovarian Hyperstimulation Syndrome with Pulmonary Presentation after In Vitro Fertilization: Case Report and Systematic Review of Case Reports.
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, usually presented in the third trimester with pruritus, elevated transaminase, and serum total bile acids. Evidence shows that it can be developed in the first trimester, more commonly after in vitro fertilization (IVF) procedures, with the presence of ovarian hyperstimulation syndrome (OHSS).
METHODS
A literature search was conducted in the PubMed/MEDLINE database of case reports/studies reporting early-onset ICP in spontaneous and IVF pregnancies published until July 2023.
RESULTS
Thirty articles on early-onset ICP were included in the review analysis, with 19 patients who developed ICP in spontaneous pregnancy and 15 patients who developed ICP in IVF pregnancies with or without OHSS. Cases of 1st and 2nd trimester ICP in terms of "early-onset" ICP were pooled to gather additional findings.
CONCLUSIONS
Proper monitoring should be applied even before expected pregnancy and during IVF procedures in patients with known risk factors for OHSS and ICP development (patient and family history), with proper progesterone supplementation dosage and genetic testing in case of ICP recurrence.
PubMed: 38255744
DOI: 10.3390/life14010129 -
Cureus Dec 2023Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an... (Review)
Review
Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an immunomodulator), belongs to the class of calcineurin inhibitors, with promising efficacy in AD. We performed this systematic review to obtain an up-to-date coverage map of controlled clinical trials of sequential or intermittent treatments with TCI as a therapeutic intervention for AD. Articles of interest were retrieved from PubMed, Google Scholar, and EMBASE published between between January 2000 and March 2023. Key words were "calcineurin inhibitors," "corticosteroids," "atopic dermatitis," "pruritus," "sequential," "intermittent" and "consecutive" while fixed language search consisted of "Intermittent topical calcineurin inhibitors AND topical corticosteroids AND atopic dermatitis OR eczema" AD patients who were administered sequential and/or intermittent applications of TCI for management of atopic eczema were included. Outcome measures included but were not limited to Scoring of Atopic Dermatitis (SCORAD) and the Eczema Area Severity Score (EASI). Four clinical trials were considered for the purpose of review. A total of 101 patients with AD were analysed. The risk of bias was low in two studies, while the other two had an unclear risk of bias. Overall, pooled data from two trials revealed that sequential therapy with TCS/TCI was comparable to monotherapy or emollients, as the test for overall effect determined was non-significant with a p-value of 0.33. The two studies were highly heterogeneous, as indicated by a very high I of 92% and an extremely significant p-value (p=0.0005). Sequential therapy with TCS and TCIs was effective and well tolerated in the management of AD and it may be considered an important treatment approach during the initial period.
PubMed: 38229798
DOI: 10.7759/cureus.50640 -
Renal Failure Dec 2024The number of clinical reports of acupuncture therapy in chronic kidney disease (CKD) is gradually increasing. This systematic review and meta-analysis aim to examine... (Meta-Analysis)
Meta-Analysis Review
The number of clinical reports of acupuncture therapy in chronic kidney disease (CKD) is gradually increasing. This systematic review and meta-analysis aim to examine the therapeutic role of acupuncture therapy in kidney function and common symptoms in CKD patients. We searched Embase, PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, WanFang, and WeiPu for randomized controlled trials comparing acupuncture treatment with control or placebo groups. We assessed the effect of acupuncture therapy in CKD patients using a meta-analysis with the hartung-knapp-sidik-jonkman random effects model. In addition, we visualized keyword co-occurrence overlay visualization with the help of VOSviewer software to describe the research hotspots of acupuncture therapy and CKD. A total of 24 studies involving 1494 participants were included. Compared to the control group, acupuncture therapy reduced serum creatinine levels (standardized mean difference [SMD]: -0.57; 95% CI -1.05 to -0.09) and relieved pruritus (SMD: -2.20; 95% CI -3.84, -0.57) in patients with CKD, while the TSA showed that the included sample size did not exceed the required information size. The included studies did not report acupuncture-related adverse events. Acupuncture is an effective and safe treatment for improving kidney function and relieving pruritic symptoms in patients with CKD, but the very low evidence may limit this conclusion. The TSA suggests that high-quality trials are needed to validate the efficacy of acupuncture therapy.
Topics: Humans; Acupuncture Therapy; China; Pruritus; Renal Insufficiency, Chronic; Kidney
PubMed: 38189090
DOI: 10.1080/0886022X.2023.2301504 -
Clinical and Translational Allergy Dec 2023Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as... (Review)
Review
BACKGROUND
Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first-line anti-inflammatory therapy for AD, but long-term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta-analysis to investigate whether MA as an add-on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD.
METHODS
We systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence.
RESULTS
A total of 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that compared with controls, oral MA as an add-on therapy was associated with significantly lower SCORAD scores (MD = -5.30, 95% CI -8.50, -1.55, p < 0.01, I = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta-analysis study (p > 0.05).
CONCLUSIONS
This meta-analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be used as an add-on therapy in the treatment of AD. However, due to the limited number of studies, results should be interpreted with caution. Further studies with a larger sample size are needed to explore the optimal protocol of MA plus TCS.
PubMed: 38146806
DOI: 10.1002/clt2.12318 -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793