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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 -
Journal of Cutaneous Medicine and... May 2024Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been... (Review)
Review
Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been employed for the treatment of keloids; however, there is no one gold standard approach. Five-fluorouracil, a potent chemotherapeutic agent, has emerged as a promising therapeutic option. Therefore, this systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focused on providing a broad overview of the use of 5-fluorouracil for the management of keloids. Forty studies (2325 patients) met inclusion criteria and investigated 5-fluorouracil for keloid management, with 19 studies (1043 patients) including a 5-fluorouracil monotherapy group. Five-fluorouracil monotherapy demonstrated consistent keloid improvement with >254 keloids injected across various anatomical regions. Five-fluorouracil monotherapy was most often compared to intralesional triamcinolone acetonide, utilizing the Patient and Observer Scar Assessment Scale and the Vancouver Scar Scale. The most common keloid parameters assessed were height, size, volume, width, length, induration, pruritus, and erythema. Five-fluorouracil monotherapy exhibited substantial improvements, with weight averages of 73% of patients experiencing >25% improvement and 67% achieving >50% improvement. Relapse rate was 16% at 27 weeks after 5-fluorouracil monotherapy treatment. Limitations included potential selection bias, language restrictions, and heterogenous data analysis among studies. Overall, our findings underscore the potential effectiveness of 5-fluorouracil monotherapy in the management of keloids, with an encouraging safety profile. Larger prospective trials are needed to determine optimal therapy or combination therapy for the management of keloids. This detailed compilation of treatment protocols, outcomes, and relapse rates stand as a valuable resource for further research and clinical applications.
PubMed: 38807454
DOI: 10.1177/12034754241256346 -
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 -
Cureus Jul 2023Uremic xerosis and chronic kidney disease (CKD)-associated pruritus (CKD-ap) are the most commonly occurring dermatological problems faced by most of the CKD patients on... (Review)
Review
Management of Uremic Xerosis and Chronic Kidney Disease (CKD)-Associated Pruritus (CKD-ap) With Topical Preparations: A Systematic Review and Implications in the Indian Context.
Uremic xerosis and chronic kidney disease (CKD)-associated pruritus (CKD-ap) are the most commonly occurring dermatological problems faced by most of the CKD patients on hemodialysis which are not only annoying and draining to the patients but also have an intense effect on patients' quality of life. The PubMed, Scopus, Google Scholar, and Web of Science databases were searched for the literature with the following search terms: uremic xerosis OR CKD-ap OR uremic pruritus AND topical therapy OR topical ointment OR natural oil from the year 2002 -2022, and finally, 22 articles were chosen to write this review. Out of 22 studies, six used pharmacological preparations and remaining 16 studies used natural oils and components. All the articles were experimental studies (Pre/Quazi/RCT/True experimental) focusing on managing itch and xerosis associated with CKD and hemodialysis by topical application. The topical agents tried in various research studies are effective in managing itch and xerosis associated with CKD. They are safe, easy to use, and without allergic reactions. Natural oils like almond, chia seed, clove, glycerin, paraffin, and virgin coconut oil are readily available in home-care settings and can be used as a nurse-led intervention. Topical preparations for uremic xerosis and pruritus are effective, safe, and easy to apply on large body surface areas without systematic side effects. Natural oil-based topical preparations are cost-effective, safe, and easy to use.
PubMed: 37641756
DOI: 10.7759/cureus.42587 -
Cureus Aug 2023Oral spironolactone has been proposed as a potential treatment for hair loss due to its antiandrogenic properties. However, the efficacy and safety of spironolactone for... (Review)
Review
Oral spironolactone has been proposed as a potential treatment for hair loss due to its antiandrogenic properties. However, the efficacy and safety of spironolactone for treating hair loss are not well-established. The objective of this study was to conduct a systematic review of the current literature on the use of oral spironolactone in female pattern hair loss. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies that assessed the efficacy and safety of oral spironolactone for treating hair loss. We searched for eligible papers in PubMed, Web of Science (ISI), Embase, and Scopus. All analyses were done using R software version 4.2.3 (R Foundation for Statistical Computing, Vienna, Austria). The overall rate of improved hair loss was 56.60%, with a higher rate of improvement (65.80%) observed in the combined therapy group compared to the monotherapy group (43.21%). However, there was significant heterogeneity in the efficacy outcomes, and hair loss did not improve or showed a modest improvement in 37.80% of all patients. The rates of adverse events reported in at least two studies were scalp pruritus or increased scurf (18.92%), menstrual disorders (11.85%), facial hypertrichosis (6.93%), and drug discontinuation (2.79%). The overall adverse events rate was 3.69%, but there was significant heterogeneity in the rates of different adverse events. In conclusion, the present study suggests that spironolactone is an effective and safe treatment option for hair loss. However, further research is needed to fully understand the heterogeneity of treatment response and adverse events and identify factors that may predict treatment response.
PubMed: 37719557
DOI: 10.7759/cureus.43559 -
Biomedical Reports May 2024Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In...
Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.
Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.
PubMed: 38628626
DOI: 10.3892/br.2024.1772 -
Cureus Jul 2023Paracetamol (acetaminophen) is an extensively used analgesic for acute and chronic pain management. Currently, paracetamol is manufactured for oral, rectal, and... (Review)
Review
Paracetamol (acetaminophen) is an extensively used analgesic for acute and chronic pain management. Currently, paracetamol is manufactured for oral, rectal, and intravenous (IV) use. Research has shown varied results on the analgesic properties of IV paracetamol compared to oral and rectal paracetamol; however, research on the same doses of paracetamol is limited. Therefore, this review was constructed to explore the analgesic properties of IV paracetamol compared with oral and rectal paracetamol administered in equivalent doses. A broad and thorough literature search was performed on five electronic databases, including PubMed, ScienceDirect, Medline, Scopus, and Google Scholar. Statistical analysis of all outcomes in our review was then performed using the Review Manager software. Outcomes were categorized as primary (pain relief and time to request rescue analgesia) and secondary (adverse events after analgesia). An extensive quality appraisal was also done using the Review Manager software's Cochrane risk of bias tool. The literature survey yielded 2,945 articles, of which 12 were used for review and analysis. The pooled analysis for patients undergoing surgical procedures showed that IV paracetamol had statistically similar postoperative pain scores at two (mean difference (MD) = -0.14; 95% confidence interval (CI) -0.58-0.29; p = 0.51), 24 (MD = 0.09; 95% CI = -0.02-0.21; p = 0.12), and 48 (MD = 0.04; 95% CI = -0.08-0.16; p = 0.52) hours as oral paracetamol. Similarly, the data on time to rescue analgesia showed no considerable difference between the IV and oral paracetamol groups (MD = -1.58; 95% CI = -5.51-2.35; p = 0.43). On the other hand, the pooled analysis for patients presenting non-surgical acute pain showed no significant difference in the mean pain scores between patients treated with IV and oral paracetamol (MD = -0.35; 95% CI = -2.19-1.48; p = 0.71). Furthermore, a subgroup analysis of analgesia-related adverse events showed that the incidences of vomiting/nausea and pruritus did not differ between patients receiving IV and oral paracetamol (odds ratio (OR) = 0.71; 95% CI = 0.45-1.11; p = 0.13 and OR = 0.48; 95% CI = 0.18-1.29; p = 0.05, respectively). A review of information from two trials comparing equal doses of IV and rectal paracetamol suggested that the postoperative pain scores were statistically similar between the groups. IV paracetamol is not superior to oral or rectal paracetamol administered in equal doses. Therefore, we cannot recommend or refute IV paracetamol as the first-line analgesia for acute and postoperative pain.
PubMed: 37581156
DOI: 10.7759/cureus.41876 -
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 -
Medicine Feb 2024Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia.
METHOD
A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes.
RESULT
Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; P < .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; P < .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; P = .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; P = .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; P > .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, P < .05; 0.39, 95% CI: 0.04-0.73, P < .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo.
CONCLUSION
OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Alanine Transaminase; Randomized Controlled Trials as Topic; Chenodeoxycholic Acid; Fibrosis; Lipoproteins, LDL; Dyslipidemias; Pruritus; Aspartate Aminotransferases; Cholesterol
PubMed: 38363900
DOI: 10.1097/MD.0000000000037271 -
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