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Patient Preference and Adherence 2020Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact... (Review)
Review
BACKGROUND
Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact pathogenesis of tissue pigmentation varies greatly and is not completely known. This systematic review aimed to present data on the causal association between medications and the development of oral/mucosal pigmentation as an adverse drug reaction.
METHODS
A systematic review and analysis of literature were conducted using the following databases: PubMed, Science Direct, ProQuest, Web of Science, and Scopus. The systematic review included original articles written in English and published between January 1982 and June 2020. Following the PRISMA statement, eligible articles were systematically reviewed, and data were extracted from eligible studies and analyzed.
RESULTS
A total of 235 articles were identified, of which 57 met the inclusion criteria and were included in this review. The mean age of included patients was 46.2±16.38 years (range: 10-90 years) with a male to female ratio of 1:1.45. Oral mucosal hyperpigmentation was reported following the use of several classes of medications such as antiviral (eg, zidovudine), antibiotic (eg, minocycline), antimalarial (eg, chloroquine), anti-fungal (eg, ketoconazole), antileprotic (eg, clofazimine), antihypertensive (eg, amlodipine), chemotherapeutic, and antineoplastic drugs. The risk of developing oral pigmentation was significantly higher with antimalarial medications, antibiotics, antineoplastic and chemotherapeutic agents. Medication-induced oral hyperpigmentation was most frequent among women and in the hard palate.
CONCLUSION
Future research is warranted to better understand the pathogenesis and risk factors for medication-induced oral hyperpigmentation in order to reassure patients during prescription and management.
PubMed: 33116439
DOI: 10.2147/PPA.S275783 -
Asia-Pacific Journal of Clinical... Feb 2023Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize... (Review)
Review
Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize factors influencing such variability. However, significant predictors for DOX pharmacokinetics identified using PopPK models varied across studies. Thus, this review aims to summarize PopPK models of DOX and its metabolites (if any) as well as significant covariates influencing DOX (and its metabolites) pharmacokinetic variability. A systematic search from PubMed, CINAHL Complete, Science Direct, and SCOPUS databases identified 503 studies. Of these, 16 studies met the inclusion criteria and were included in this review. DOX pharmacokinetics was described with two- or three-compartment models. Most studies found a significant increase in DOX clearance with an increase in body surface area from the median value of 1.8 m . Moreover, this review identified that while a 10-year increase in patient age resulted in a decrease in DOX clearance in adults and the elderly, younger children had lower DOX clearance compared to older children. Further, low DOX exposure was observed in pregnant women, and thus dosage adjustment is required. Concerning model applicability, predictive performance assessment of these published models should be performed before implementing such models in clinical practice.
Topics: Pregnancy; Adult; Child; Humans; Female; Adolescent; Aged; Models, Biological; Doxorubicin; Databases, Factual
PubMed: 35415961
DOI: 10.1111/ajco.13776 -
The Journal of Dermatological Treatment Feb 2022For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several reports of the off-label use of mycophenolate mofetil (MMF) in patients with LPP or have developed adverse effects to initial agents.
METHODS
A systematic review and meta-analysis was performed according to recommended Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies with ≥5 cases reporting the outcomes of MMF in LPP were pooled and a meta-analysis of proportion was performed. Case reports were excluded from analysis.
RESULTS
A total of six studies were identified and included for meta-analysis, comprising 94 LPP patients. The pooled proportion of any good response (partial or complete) was 69.2% (95% confidence interval (CI): 47.8-77). The pooled proportion of complete response was 20% (95% CI: 10.1-36.3). The pooled proportion of partial responses was 49.2% (95% CI: 30.5-63.7). Side effects occurred in 16.9% (95% CI: 17.6-33.2). of cases, which included elevated LFTs, edema, hyperlipidemia, anemia, herpes zoster infection, photosensitivity, and urinary tract infection.
CONCLUSION
The current evidence for MMF remains limited. However, it appears to be a potential treatment option for patients with severe or recalcitrant LPP who have failed hydroxychloroquine and other immunosuppressants.
Topics: Humans; Hydroxychloroquine; Immunosuppressive Agents; Lichen Planus; Mycophenolic Acid; Remission Induction
PubMed: 32281437
DOI: 10.1080/09546634.2020.1755416 -
BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
European Urology Focus May 2023The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted.
OBJECTIVE
To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy.
EVIDENCE ACQUISITION
Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin.
EVIDENCE SYNTHESIS
Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment.
CONCLUSIONS
Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach.
PATIENT SUMMARY
Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.
Topics: Humans; Aged; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Mitomycin; Gemcitabine; Administration, Intravesical
PubMed: 36517409
DOI: 10.1016/j.euf.2022.12.003 -
European Journal of Gastroenterology &... Feb 2018The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this treatment. The aim of this study is to evaluate the efficacy of second-line immunosuppressive therapies for AIH through a systematic review and meta-analysis in adult patients.
PATIENTS AND METHODS
The systematic review was registered at the PROSPERO platform under number 42015019831. Databases MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms were linked with each immunosuppressant of interest.
RESULTS
A total of 1532 studies were identified. Of these, 1492 were excluded on the basis of title and abstract reading. Among the 40 studies retrieved for detailed full-text analysis, a total of 15 fulfilled the inclusion criteria for the analysis. The most studied second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For MM/prednisone, the mean rate of histological remission was 88.6%, liver transplantation was indicated in 11.4%, and the mortality rate was 7.2%. Limitations were also present, such as the lack of randomized-controlled trials and prospective studies, the small number of patients, and the heterogeneity between remission criteria.
CONCLUSION
This is the first systematic review and meta-analysis to compare the second-line imunossupressant therapy for AIH. The most studied second-line immunosuppressive is the MM, with a reasonable histological remission. The use of combined tacrolimus/prednisone was the most effective for the normalization of aminotransferases.
Topics: Anti-Inflammatory Agents; Budesonide; Cyclophosphamide; Drug Therapy, Combination; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Retreatment; Tacrolimus
PubMed: 29227329
DOI: 10.1097/MEG.0000000000001019 -
Medicine Nov 2023There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines.
METHODS
PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis.
RESULTS
Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin.
CONCLUSION
Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.
Topics: Humans; Anthracyclines; Arrhythmias, Cardiac; Antibiotics, Antineoplastic; Doxorubicin; Tachycardia; Leukemia, Myeloid, Acute
PubMed: 37986405
DOI: 10.1097/MD.0000000000035770 -
Current Problems in Cardiology Oct 2023Anthracycline chemotherapy causes cardiotoxicity, and the evidence regarding the benefit of concomitant statin use in reducing it remains uncertain. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Anthracycline chemotherapy causes cardiotoxicity, and the evidence regarding the benefit of concomitant statin use in reducing it remains uncertain. We conducted a meta-analysis of studies using statins and anthracyclines by searching PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until April 10, 2023. Our analysis included 3 observational studies and 4 RCTs, including the STOP-CA trial released in ACC23. Statin prescription significantly reduced cardiotoxicity in cancer patients receiving anthracycline chemotherapy (OR 0.46, 95% CI: 0.33-0.63; I2: 0%). However, no significant difference was observed in the decline of left ventricular ejection fraction (LVEF) from baseline (MD 4.15, 95% CI: -0.69 to 8.99, I2: 97%). These findings demonstrate the protective effect of concomitant statin prescription.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiotoxicity; Stroke Volume; Ventricular Function, Left; Anthracyclines; Antibiotics, Antineoplastic; Observational Studies as Topic
PubMed: 37336312
DOI: 10.1016/j.cpcardiol.2023.101885 -
The Cochrane Database of Systematic... May 2019Orbital lymphangiomas are a subset of localized vascular and lymphatic malformations, which most commonly occur in the head and neck region. Orbital lymphangiomas...
BACKGROUND
Orbital lymphangiomas are a subset of localized vascular and lymphatic malformations, which most commonly occur in the head and neck region. Orbital lymphangiomas typically present in the first decade of life with signs of ptosis, proptosis, restriction of ocular motility, compressive optic neuropathy, and disfigurement. Therefore, early and effective treatment is crucial to preserving vision. Due to proximity to vital structures, such as the globe, optic nerve, and extraocular muscles, treatment for these lesions is complicated and includes a large array of approaches including observation, sclerotherapy, systemic therapy, and surgical excision. Of these options, there is no clear gold standard of treatment.
OBJECTIVES
To assess the evidence supporting medical and surgical interventions for the reduction/treatment of orbital lymphangiomas in children and young adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 5); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 May 2018.
SELECTION CRITERIA
We planned to include randomized controlled trials (RCTs) comparing at least two of the following interventions with each other for the treatment of orbital lymphangiomas: observation; sildenafil therapy; sirolimus therapy; sclerotherapy; surgery (partial or complete resection). We planned to include trials that enrolled children and adults up to 32 years of age, based on a prior clinical trial protocol. There were no restrictions regarding location or demographic factors.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles, abstracts, and full articles to assess their suitability for inclusion in this review. No risk of bias or data extraction was performed because we did not find any trials for inclusion. If there had been RCTs, two authors would have assessed the risk of bias and abstracted data independently with discrepancies being settled by consensus or consultation with a third review author.
MAIN RESULTS
There were no RCTs that compared any two of the mentioned interventions (medical or surgical) for treating orbital lymphangiomas in children and young adults.
AUTHORS' CONCLUSIONS
Currently, there are no published RCTs of orbital lymphangioma treatments. Without these types of studies, conclusions cannot be drawn regarding the effectiveness of the medical and surgical treatment options for patients with orbital lymphangiomas. The presence of only case reports and case series on orbital lymphangiomas makes it clear that RCTs are needed to address the differences between these options and help guide treatment plans. Such trials would ideally compare outcomes between individuals randomized to one of the following treatment options: observation, sclerotherapy, systemic sirolimus therapy, systemic sildenafil therapy, and surgical excision.
Topics: Antibiotics, Antineoplastic; Humans; Lymphangioma; Orbital Neoplasms; Treatment Outcome
PubMed: 31094450
DOI: 10.1002/14651858.CD013000.pub2