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Drug Design, Development and Therapy 2023Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to... (Review)
Review
Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to chronic pain. Opioids have traditionally been the mainstay for treatment of moderate to severe acute pain. However, their use has been associated with opioid-related adverse events (ORAEs), such as respiratory depression, sedation, nausea, vomiting, pruritus, and decreased bowel motility. In addition, their liberal use has been implicated in the current opioid epidemic. As a result, there has been renewed interest in multimodal analgesia to target different mechanisms of action in order to achieve a synergistic effect and minimize opioid usage. Oliceridine is a novel mu-opioid receptor agonist that is part of a new class of biased ligands that selectively activate G-protein signaling and downregulate β-arrestin recruitment. Since G-protein signaling has been associated with analgesia while β-arrestin recruitment has been associated with ORAEs, there is potential for a wider therapeutic window. In this review, we will discuss the clinical evidence behind oliceridine and its potential role in acute postoperative pain management. We have systematically searched the PubMed database using the keywords , and . All articles identified were reviewed and evaluated, and all clinical trials were included.
Topics: Humans; Analgesics, Opioid; Morphine; Pain, Postoperative; GTP-Binding Proteins
PubMed: 36987403
DOI: 10.2147/DDDT.S372612 -
Frontiers in Medicine 2022Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved...
INTRODUCTION
Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.
OBJECTIVE
To evaluate the effect of AD treatments on pruritus.
METHODS
A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.
RESULTS
Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32-4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58-3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).
DISCUSSION
The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.
PubMed: 36619624
DOI: 10.3389/fmed.2022.1079323 -
Journal of the American Academy of... Dec 2019Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine...
Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine primarily drives itch (pruritus), cholestatic pruritus is multifactorial and more difficult to treat. Existing therapies are not always effective and have undesirable adverse effect profiles. Here, we conducted a systematic literature review to evaluate conventional treatment strategy, current pathophysiologic understanding, and the role of new therapies in the context of cholestatic pruritus. We discuss novel findings implicating bile acids, lysophosphatidic acid, and bilirubin as potential important mediators of cholestatic itch. New therapies that aim to remove or modulate pruritogens have been supported in observational cohort studies and randomized controlled trials. Although these new therapies show promise, further research is needed to confirm the pathophysiology of cholestatic pruritus so that targeted therapy can be developed.
Topics: Cholestasis; Humans; Pruritus
PubMed: 31009666
DOI: 10.1016/j.jaad.2019.04.035 -
JMIR Dermatology Nov 2023Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema.... (Review)
Review
BACKGROUND
Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema. Dissatisfaction with first-line therapies for AD, the desire to avoid steroids, and the extreme cost of effective biologics have created a demand for alternative treatment options such as oral vitamins and nutritional supplements.
OBJECTIVE
The purpose of this review was to assess the effectiveness of oral nutritional supplements, pre- and probiotics, and vitamin deficiencies and supplements on AD symptomology and clinical course.
METHODS
We searched Scopus, PubMed, and MEDLINE (Ovid interface) for English-language articles published between 1993 and 2023. The final search was conducted on June 22, 2023. The search terms comprised the following: "(Atopic Dermatitis or Atopic Eczema) AND (supplement OR vitamin OR mineral OR micronutrients OR Fish Oil OR Omega Fatty Acid OR Probiotics OR Prebiotics OR apple cider vinegar OR collagen OR herbal OR fiber)."
RESULTS
A total of 18 studies-3 (17%) evaluating vitamins, 4 (22%) evaluating herbal medicine compounds, 2 (11%) evaluating single-ingredient nutritional supplements, and 9 (50%) evaluating pre- and probiotics-involving 881 patients were included in this review.
CONCLUSIONS
Overall, there is weak evidence to support any one nutritional supplement intervention for the alleviation of AD symptoms. Multiple trials (4/18, 22%) showed promise for supplements such as Zemaphyte, kefir, and freeze-dried whey with Cuscuta campestris Yuncker extract. The most evidence was found on the effectiveness of probiotics on the clinical course of AD. Lactiplantibacillus plantarum, Ligilactobacillus salivarius, and Lactobacillus acidophilus specifically showed evidence of efficacy and safety across multiple studies (6/18, 33%). However, larger, more extensive randomized controlled trials are needed to determine the true effectiveness of these supplements on the broader population.
TRIAL REGISTRATION
PROSPERO CRD42023470596; https://tinyurl.com/4a9477u7.
PubMed: 38019566
DOI: 10.2196/40857 -
British Journal of Clinical Pharmacology Jul 2023New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial... (Review)
Review
AIM
New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial literature and concisely report the updated safety and adverse effects of topical medications used to treat atopic dermatitis in children.
METHODS
A systematic search of Cochrane Library, Embase, PubMed and ClinicalTrials.gov from inception to March 2022 was conducted for trials of topical medications used to treat AD in patients <18 years (PROSPERO #CRD42022315355). Included records were limited to English-language publications and studies of ≥3 weeks duration. Phase 1 studies and those that lacked separate paediatric safety reporting were excluded.
RESULTS
A total of 5005 records were screened; 75 records met inclusion criteria with 15 845 paediatric patients treated with tacrolimus, 12 851 treated with pimecrolimus, 3539 with topical corticosteroid (TCS), 700 with crisaborole and 202 with delgocitinib. Safety data was well reported in tacrolimus trials with the most frequently reported adverse events being burning sensation, pruritus and cutaneous infections. Two longitudinal cohort studies were included, one for tacrolimus and one for pimecrolimus, which found no significant increased risk of malignancy with topical calcineurin inhibitor (TCI) use in children. Skin atrophy was identified as an adverse event in TCS trials, which other medications did not. Systemic adverse events for the medications were largely common childhood ailments.
CONCLUSION
Data discussed here support the use of steroid-sparing medications (tacrolimus, pimecrolimus, crisaborole, delgocitinib) as safe options with minimal adverse events for managing paediatric AD, although a larger number of TCI studies reported burning and pruritus compared to TCS studies. TCS was the only medication class associated with reports of skin atrophy in this review. The tolerability of these adverse events should be considered when treating young children. This review was limited to English-language publications and the variable safety reporting of trial investigators. Many newer medications were not included due to pooled adult and paediatric safety data that did not meet inclusion criteria.
Topics: Adult; Child; Humans; Child, Preschool; Dermatitis, Atopic; Tacrolimus; Longitudinal Studies; Calcineurin Inhibitors; Dermatologic Agents; Pruritus; Treatment Outcome
PubMed: 37075252
DOI: 10.1111/bcp.15751 -
Frontiers in Immunology 2023Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better...
BACKGROUND
Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab.
OBJECTIVE
The objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis.
METHODS
Several databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study.
RESULTS
After 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119).
CONCLUSIONS
Dupilumab has definite effectiveness and safety in prurigo nodularis treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).
Topics: Humans; Prurigo; Pruritus; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 36742321
DOI: 10.3389/fimmu.2023.1092685 -
Virology Journal Nov 2023The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.
METHODS
Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.
RESULTS
Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.
CONCLUSION
Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.
Topics: Humans; Oncolytic Virotherapy; Granulocyte-Macrophage Colony-Stimulating Factor; Immunotherapy; Melanoma; Oncolytic Viruses; Pain
PubMed: 37919738
DOI: 10.1186/s12985-023-02220-x -
Journal of Physiotherapy Jan 2024In adults with a burn injury, do non-invasive therapies improve pain and burn scar pruritus, elasticity and vascularisation? Are any effects maintained beyond the...
QUESTIONS
In adults with a burn injury, do non-invasive therapies improve pain and burn scar pruritus, elasticity and vascularisation? Are any effects maintained beyond the intervention period?
DESIGN
Systematic review of randomised trials with meta-analyses.
PARTICIPANTS
Adults with burn scars.
INTERVENTION
The experimental intervention was a non-invasive (ie, non-surgical or non-pharmacological) therapy applied to the burn scar.
OUTCOME MEASURES
Pain intensity, pruritus intensity, elasticity and vascularisation.
RESULTS
Fifteen trials involving 780 participants were included. The results indicated a beneficial effect on pain intensity on a 0-to-10 scale after massage (MD -1.5, 95% CI -1.8 to -1.1), shockwave therapy (MD -0.8, 95% CI -1.2 to -0.4) and laser (MD -4.0, 95% CI -6.0 to -2.0). The results indicated a beneficial effect on pruritus intensity on a 0-to-10 scale after massage (MD -0.4, 95% CI -0.7 to -0.2), shockwave therapy (MD -1.3, 95% CI -2.3 to -0.3) and laser (MD -4.8, 95% CI -6.1 to -3.5). Massage, shockwave therapy and silicone produced negligible or unclear benefits on scar elasticity and vascularisation. The quality of evidence varied from low to moderate.
CONCLUSION
Among all commonly used non-invasive therapies for the treatment of burn scars, low-to-moderate quality evidence indicated that massage, laser and shockwave therapy reduce pain and the intensity of scar pruritus. Low-to-moderate quality evidence suggested that massage, shockwave therapy and silicone have negligible or unclear effects for improving scar elasticity and vascularisation.
REVIEW REGISTRATION
PROSPERO (CRD42021258336).
Topics: Adult; Humans; Cicatrix, Hypertrophic; High-Energy Shock Waves; Pruritus; Pain; Lasers; Burns; Massage; Silicones
PubMed: 38072714
DOI: 10.1016/j.jphys.2023.10.010 -
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 -
Therapeutic Advances in Medical Oncology 2023Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new... (Review)
Review
BACKGROUND
Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs).
OBJECTIVE
We aimed to assess the frequency of AEs associated with DT.
DESIGN
This study type is a systematic review and meta-analysis.
DATA SOURCES AND METHODS
Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751).
RESULTS
Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups.
CONCLUSIONS
The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.
PubMed: 37720498
DOI: 10.1177/17588359231198453