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Journal Der Deutschen Dermatologischen... Jun 2023Various interventions have been applied to treat molluscum contagiosum, but benefits and efficacy remain unclear. To assess the comparative efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Various interventions have been applied to treat molluscum contagiosum, but benefits and efficacy remain unclear. To assess the comparative efficacy and safety of interventions for molluscum contagiosum, a network meta-analysis was performed.
PATIENTS AND METHODS
Embase, PubMed, and the Cochrane Library were searched for articles published between January 1, 1990, and November 31, 2020. Eligible studies were randomized clinical trials (RCTs) of interventions in immunocompetent children and adults with genital/non-genital molluscum contagiosum lesions.
RESULTS
Twelve interventions from 25 RCTs including 2,123 participants were assessed. Compared with the placebo, ingenol mebutate had the most significant effect on complete clearance (odds ratio [OR] 117.42, 95% confidence interval [CI] 6.37-2164.88), followed by cryotherapy (OR 16.81, 95% CI 4.13-68.54), podophyllotoxin (OR 10.24, 95% CI 3.36-31.21), and potassium hydroxide (KOH) (OR 10.02, 95% CI 4.64-21.64). Data on adverse effects were too scarce for quantitative synthesis.
CONCLUSIONS
Ingenol mebutate, cryotherapy, podophyllotoxin, and KOH were more effective than the other interventions in achieving complete clearance, but safety concerns regarding ingenol mebutate have recently been reported. Due to the possibility of spontaneous resolution, observation is also justified for asymptomatic infection. Factors including adverse effects, cost, patient preference, and medical accessibility should be considered.
Topics: Child; Adult; Humans; Molluscum Contagiosum; Podophyllotoxin; Network Meta-Analysis; Cryotherapy; Randomized Controlled Trials as Topic
PubMed: 37199262
DOI: 10.1111/ddg.15063 -
Pediatric Blood & Cancer Mar 2023Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed.
DATA SOURCES
PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022.
STUDY SELECTION
Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU.
DATA EXTRACTION
Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed.
DATA SYNTHESIS
Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47).
CONCLUSION
Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.
Topics: Humans; Child; Child, Preschool; Lymphohistiocytosis, Hemophagocytic; Etoposide; Critical Illness; Retrospective Studies; Intensive Care Units, Pediatric; Immunoglobulins, Intravenous
PubMed: 36579732
DOI: 10.1002/pbc.30122 -
JAMA Network Open Oct 2020Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is.
OBJECTIVE
To clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC.
DATA SOURCES
Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019.
STUDY SELECTION
Head-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
Main outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5.
RESULTS
A total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposide-platinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the cumulative ranking curve value, PD-L1 inhibitor plus etoposide-platinum had the highest probability of being ranked first for OS (0.87) and DCR (0.97).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and network meta-analysis suggest that the combination of a PD-L1 inhibitor (durvalumab and atezolizumab) and etoposide-based chemotherapy may be an optimal first-line treatment option for patients with ES-SCLC patients.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Etoposide; Female; Humans; Immunotherapy; Lung Neoplasms; Male; Middle Aged; Small Cell Lung Carcinoma
PubMed: 33074323
DOI: 10.1001/jamanetworkopen.2020.15748 -
European Journal of Cancer (Oxford,... Mar 2022Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of... (Review)
Review
Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Etoposide; Humans; Infant; Infant, Newborn
PubMed: 34865945
DOI: 10.1016/j.ejca.2021.11.001 -
Supportive Care in Cancer : Official... Jun 2023There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis.
METHODS
Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426).
RESULTS
A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients.
CONCLUSION
In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.
Topics: Humans; Catheters; China; Databases, Factual; Etoposide; Neoplasms
PubMed: 37314592
DOI: 10.1007/s00520-023-07855-8 -
Cell Transplantation 2023High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma... (Meta-Analysis)
Meta-Analysis
BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52-0.94, = 0.02], lower RR (0.49, 95% CI, 0.31-0.76, = 0.002), higher mucositis (3.43, 95% CI, 2.29-5.16, = 0.001), renal toxicity (4.49, 95% CI, 2.68-7.51, = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03-3.40, = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD -0.64, 95% CI, -1.46 to 0.18, = 0.13), PE (pooled WMD -0.3, 95% CI, -1.68 to 2.28, = 0.77), OS (0.73, 95% CI, 0.52-1.01, = 0.07), and NRM (1.51, 95% CI, 0.76-2.98, = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.
Topics: Humans; Carmustine; Transplantation, Autologous; Bendamustine Hydrochloride; Hematopoietic Stem Cell Transplantation; Cytarabine; Etoposide; Melphalan; Cardiotoxicity; Mucositis; Retrospective Studies; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin
PubMed: 37350429
DOI: 10.1177/09636897231179364 -
BMJ Open Oct 2019To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal and synthesis of data from randomised controlled trials (RCTs).
DESIGN
Systematic review and network meta-analysis of RCTs. Search strategies were developed for MEDLINE, Embase, the Cochrane Library and the Web of Science. For electronic databases, searches were run from inception to March 2018. The systematic review was carried out following the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
PARTICIPANTS
People aged ≥16 years with clinically diagnosed AGWs (irrespective of biopsy confirmation).
INTERVENTIONS
Topical and ablative treatments recommended by the British Association for Sexual Health and HIV for the treatment of AGWs, either as monotherapy or in combination versus each other.
OUTCOME MEASURES
Complete clearance of AGWs at the end of treatment and at other scheduled visits, and rate of recurrence.
RESULTS
Thirty-seven RCTs met inclusion criteria. Twenty studies were assessed as being at unclear risk of bias, with the remaining studies categorised as high risk of bias. Network meta-analysis indicates that, of the treatment options compared, carbon dioxide laser therapy is the most effective treatment for achieving complete clearance of AGWs at the end of treatment. Of patient-applied topical treatments, podophyllotoxin 0.5% solution was found to be the most effective at achieving complete clearance, and was associated with a statistically significant difference compared with imiquimod 5% cream and polyphenon E 10% ointment (p<0.05). Few data were available on recurrence of AGWs after complete clearance. Of the interventions evaluated, surgical excision was the most effective at minimising risk of recurrence.
CONCLUSION
Of the studies assessed, as a collective, the quality of the evidence is low. Few studies are available that evaluate treatment options versus each other.
TRIAL REGISTRATION NUMBER
CRD42013005457.
Topics: Administration, Topical; Antineoplastic Agents; Anus Diseases; Catechin; Caustics; Condylomata Acuminata; Cryosurgery; Electrosurgery; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Imiquimod; Laser Therapy; Male; Network Meta-Analysis; Papillomaviridae; Podophyllotoxin; Treatment Outcome; Trichloroacetic Acid
PubMed: 31676644
DOI: 10.1136/bmjopen-2018-027765 -
Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392 -
Clinics in Dermatology 2021Although molluscum contagiosum (MC) is a common infectious dermatosis that is self-resolving, treatment can diminish discomfort and decrease the risk of autoinoculation...
Although molluscum contagiosum (MC) is a common infectious dermatosis that is self-resolving, treatment can diminish discomfort and decrease the risk of autoinoculation and infection to others, because it is transmitted through direct skin contact. This systematic review evaluates the efficacy of topical treatments for MC. A PubMed search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed to find randomized, controlled trials of MC treatment. The search yielded 129 publications, but only 15 studies published between 1994 and 2020 were found to fit the inclusion criteria. Treatment modalities included podophyllotoxin, imiquimod, sodium nitrite, myrtle leaf extract, phenol, Salatac Gel (salicylic acid with lactic acid), potassium hydroxide, cantharidin, SB206, and VP-102. Outcomes were extracted from the literature, and subsequent quality and risk of bias assessments were performed. All treatments were more efficacious than the control except cantharidin, potassium hydroxide, and imiquimod, which had varying degrees of efficacy throughout studies. Overall, studies were of sufficient quality and had low risk of bias, but they had small sample sizes and lacked adequate explanation of statistical analysis. Current first-line treatment entails mechanical methods such as cryotherapy and curettage, which may be frightening to children with MC, so the development and assessment of topical treatments allows for alternative efficacious techniques.
Topics: Child; Humans; Molluscum Contagiosum; Randomized Controlled Trials as Topic
PubMed: 34920817
DOI: 10.1016/j.clindermatol.2021.07.002 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6