-
Journal of Comparative Effectiveness... Dec 2019To conduct a systematic literature review of high-risk resectable cutaneous melanoma adjuvant therapeutics and compare safety and efficacy. The systematic literature... (Comparative Study)
Comparative Study Meta-Analysis
To conduct a systematic literature review of high-risk resectable cutaneous melanoma adjuvant therapeutics and compare safety and efficacy. The systematic literature review included randomized controlled trials investigating: dabrafenib plus trametinib (DAB + TRAM), nivolumab, pembrolizumab, ipilimumab, vemurafenib, chemotherapy and interferons. Outcomes included overall survival (OS), relapse-free survival, distant metastasis-free survival and safety. All outcomes were synthesized using Bayesian network meta-analysis. Across relapse-free survival, distant metastasis-free survival and OS, DAB + TRAM had the lowest estimated hazards of respective events relative to all other treatments (exception relative to nivolumab in OS). Differences were significant relative to placebo, chemotherapy, interferons and ipilimumab. DAB + TRAM has improved efficacy over historical treatment options (ipilimumab, interferons and chemotherapy) and comparable efficacy with other targeted and immune checkpoint inhibitors.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Imidazoles; Interferons; Ipilimumab; Male; Melanoma; Middle Aged; Neoplasm Recurrence, Local; Network Meta-Analysis; Nivolumab; Oximes; Pyridones; Pyrimidinones; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome; Vemurafenib
PubMed: 31778073
DOI: 10.2217/cer-2019-0061 -
Cancer Treatment Reviews Mar 2019The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level.
METHODS
The literature review included searches of MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) to November 2018. Randomized controlled trials of previously untreated patients with advanced melanoma were eligible if at least one intervention was either a targeted or immune therapy. Relative treatment effects were estimated by fixed effect Bayesian NMAs on progression-free survival (PFS) and overall survival (OS), based on the hazard ratio.
RESULTS
Combination dabrafenib with trametinib (HR 0.22 [95% CrI 0.17, 0.28] vs dacarbazine) and combination vemurafenib with cobimetinib (HR 0.22 [95% CrI 0.17, 0.29] vs dacarbazine) were likely to rank as the most favorable treatment options for PFS, while combination nivolumab with ipilimumab was likely to be the most efficacious in terms of OS (HR 0.33 [0.24, 0.47] vs dacarbazine).
CONCLUSIONS AND RELEVANCE
The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma. However, as few trials informed each treatment comparison, research is needed to further refine our understanding of this complex and rapidly evolving treatment landscape.
Topics: Antineoplastic Combined Chemotherapy Protocols; Azetidines; Dacarbazine; Humans; Imidazoles; Melanoma; Molecular Targeted Therapy; Mutation; Oximes; Piperidines; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Randomized Controlled Trials as Topic; Vemurafenib
PubMed: 30798169
DOI: 10.1016/j.ctrv.2019.02.001 -
Journal of Comparative Effectiveness... Mar 2021The objective was to systematically review the literature and assess the relative efficacy of agents approved in first-line settings via network meta-analysis. A... (Meta-Analysis)
Meta-Analysis
The objective was to systematically review the literature and assess the relative efficacy of agents approved in first-line settings via network meta-analysis. A literature review was conducted via searching different medical databases. The eligibility criteria included Phase II or III randomized controlled trials that had enrolled treatment-naive adult patients with advanced/metastatic melanoma. The network meta-analysis results suggested that dabrafenib + trametinib significantly prolongs the survival outcomes compared with the monotherapies and had comparable efficacy profile compared with encorafenib + binimetinib and cobimetinib + vemurafenib. In comparison with immunotherapies, the results varied for progression-free survival and overall survival. Long-term survival data of dabrafenib + trametinib establishes the combination as one of the preferred treatment options for previously untreated melanoma patients.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Imidazoles; Melanoma; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones
PubMed: 33448878
DOI: 10.2217/cer-2020-0249 -
BMC Veterinary Research Jan 2019Canine generalised demodicosis is an inflammatory parasitic skin disease caused by an excessive proliferation of Demodex spp. Generalized demodicosis is a severe skin...
BACKGROUND
Canine generalised demodicosis is an inflammatory parasitic skin disease caused by an excessive proliferation of Demodex spp. Generalized demodicosis is a severe skin disease, that can be life threatening if not treated properly. Many of the current treatment options are not licensed for the treatment of generalised demodicosis, it have a low safety margin and may be poorly efficacious and time-consuming for the owner; there is a need for a safe, efficacious treatment for canine demodicosis. Our objective was to systematically review the literature to determine the most effective and safe topical or systemic therapy for canine generalised demodicosis. Single case reports and case series with fewer than five patients were not reviewed as they were considered to be poor quality evidence. A detailed literature search identified 21 relevant clinical trials and these were critically assessed.
RESULTS
The analysis of the best available evidence on March 5, 2018, suggests that six are the most effective and safe treatments for generalised canine demodicosis including (in alphabetical order): doramectin (oral or parenteral); fluralaner (oral); imidacloprid/moxidectin (topical); ivermectin (oral, not as first choice treatment); milbemycin oxime (oral); and sarolaner (oral). There was insufficient evidence to allow comment on the appropriateness of other treatment protocols for canine generalised demodicosis in this CAT.
CONCLUSIONS
In our critical appraisal of the best scientific literature, there is evidence for recommending the use of 6 therapeutic options against demodectic mange. Further, in vivo, controlled, randomized and blinded clinical trials are required, to evaluate new therapies.
Topics: Acaricides; Animals; Azetidines; Dog Diseases; Dogs; Isoxazoles; Ivermectin; Macrolides; Mite Infestations; Mites; Spiro Compounds
PubMed: 30616591
DOI: 10.1186/s12917-018-1767-7 -
International Clinical... Mar 2019The purpose of this study was to conduct a systematic review of the pharmacological options available to treat patients diagnosed with attention-deficit hyperactivity...
The purpose of this study was to conduct a systematic review of the pharmacological options available to treat patients diagnosed with attention-deficit hyperactivity disorder and anxiety disorder, for generating evidence on the safest, most-effective and tolerable pharmacotherapy. To this end, a systematic search was performed in three electronic databases (Medline, Scopus and Directory of Open Access Journals; December 2017). Randomized, double-blind, parallel-design clinical trials evaluating the efficacy, safety or tolerability of therapies for attention-deficit hyperactivity disorder and anxiety disorder in children and adolescents or adults were considered. A total of 1960 articles were retrieved from the databases, of which five studies were included in the qualitative synthesis. Two of these studies evaluated the drug atomoxetine, another study evaluated desipramine, and the remaining two studies evaluated methylphenidate, with fluvoxamine being associated with methylphenidate in one of the trials. Owing to the high heterogeneity among studies, it was not possible to combine data for meta-analyses. Although only few studies have been evaluated in this systematic review, the results point to a more significant benefit of atomoxetine. This is probably because this drug was studied in a wider age range and evaluated by more specific scales for both disorders. To further strengthen this evidence, randomized, controlled and multicenter clinical trials with larger sample sizes should be conducted.
Topics: Adolescent; Adult; Anxiety Disorders; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Agents; Child; Comorbidity; Desipramine; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Methylphenidate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30422834
DOI: 10.1097/YIC.0000000000000243 -
Journal of Medical Toxicology :... Mar 2018Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role... (Meta-Analysis)
Meta-Analysis
Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role of atropine is well-established for patients with acute OP poisoning. The benefit of adding 2-pyridine aldoxime methyl chloride (2-PAM), however, is controversial. We performed a systematic review and meta-analysis of available randomized controlled trials (RCT) to compare 2-PAM plus atropine in comparison to atropine alone for acute OP poisoning. We searched PubMed, EMBASE, and SCOPUS up to March 2017. The Cochrane review handbook was used to assess the risk of bias. Data were abstracted and risk ratios (RR) were calculated for mortality, rate of intubation, duration of intubation, intermediate syndrome, and complications such as hospital-acquired infections, dysrhythmias, and pulmonary edema. We found five studies comprising 586 patients with varying risks of bias. The risk of death (RR = 1.5, 95% CI 0.9-2.5); intubation (RR = 1.3, 95% CI 1.0-1.6); intermediate syndrome (RR = 1.6, 95% CI 1.0-2.6); complications (RR = 1.2, 95% CI 0.8-1.8); and the duration of intubation (mean difference 0.0, 95% CI - 1.6-1.6) were not significantly different between the atropine plus 2-PAM and atropine alone. Based on our meta-analysis of the available RCTs, 2-PAM was not shown to improve outcomes in patients with acute OP poisoning.
Topics: Animals; Antidotes; Cholinesterase Reactivators; Humans; Organophosphate Poisoning; Pralidoxime Compounds
PubMed: 29230717
DOI: 10.1007/s13181-017-0636-2 -
Melanoma Research Oct 2019Disseminated intravascular coagulation is a complex and potentially lethal complication of malignancy, in which the fundamental abnormality is excessive activation of...
Disseminated intravascular coagulation is a complex and potentially lethal complication of malignancy, in which the fundamental abnormality is excessive activation of the coagulation system. It is a rare complication of melanoma which can be difficult to diagnose in some circumstances, leading to delay in treatment. Herein, we describe the first case of disseminated intravascular coagulation occurring in BRAF and NRAS-mutant metastatic melanoma, and systematically review the literature regarding disseminated intravascular coagulation in melanoma. This review summarizes the reported cases of disseminated intravascular coagulation in melanoma and those secondary to the novel treatment of melanoma, and explores the pathophysiology of disseminated intravascular coagulation in melanoma, highlighting the key role of expression of markers of coagulation and fibrinolysis in disseminated intravascular coagulation, as well as more widely in melanoma. Current limitations in the literature are also identified and discussed, particularly with respect to improving the management of this lethal complication. Disseminated intravascular coagulation is a rare complication of melanoma that typically portends poor prognosis.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Disseminated Intravascular Coagulation; Female; Fibrinolysis; GTP Phosphohydrolases; Humans; Imidazoles; Melanoma; Membrane Proteins; Mutation; Neoplasm Metastasis; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms; Treatment Outcome
PubMed: 31095038
DOI: 10.1097/CMR.0000000000000622 -
Value in Health : the Journal of the... Nov 2014
PubMed: 27202720
DOI: 10.1016/j.jval.2014.08.195 -
Journal of the American Academy of... Feb 2024
Topics: Humans; Proto-Oncogene Proteins B-raf; Melanoma; Protein Kinase Inhibitors; Panniculitis; Antineoplastic Combined Chemotherapy Protocols; Mutation; Skin Neoplasms; Pyridones; Oximes
PubMed: 37943239
DOI: 10.1016/j.jaad.2023.10.008 -
PloS One 2020RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its...
Exploring the utility of RDoC in differentiating effectiveness amongst antidepressants: A systematic review using proposed psychometrics as the unit of analysis for the Negative Valence Systems domain.
BACKGROUND
RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its clinical utility remains controversial.
AIM
To explore RDoC's potential clinical utility by examining antidepressant effectiveness through Negative Valence Systems (NVS) domain constructs.
METHOD
A systematic review was conducted on Web of Science, MEDLINE, EMBASE and PsycINFO for antidepressant trials that included psychometric instruments assessed by Watson, Stanton & Clark (2017) to represent NVS constructs of Acute Threat, Potential Threat and Loss.
RESULTS
221 citations were identified; 13 were included in qualitative synthesis, none for quantitative analysis. All suffered from significant bias risks. 9 antidepressants were investigated, most within 1 construct, and most were found to be effective. Paroxetine, citalopram and fluvoxamine were found to be effective for Acute Threat, fluoxetine, desvenlafaxine and sertraline for Potential Threat, and sertraline, fluvoxamine, fluoxetine and desvenlafaxine effective for Loss. Nefazodone was found to be ineffective for acute fear.
CONCLUSION
Preliminary evidence supports RDoC NVS constructs' clinical utility in assessing antidepressant effectiveness, but lack of discriminant validity between Potential Threat and Loss supports their recombination into a single Distress construct. Finding of effectiveness within "normal" construct levels support the utility of a dimensional approach. Testable hypotheses were generated that can further test RDoC's clinical utility.
Topics: Algorithms; Antidepressive Agents; Citalopram; Clinical Trials as Topic; Depressive Disorder; Desvenlafaxine Succinate; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Psychometrics; Sertraline; Treatment Outcome
PubMed: 33326436
DOI: 10.1371/journal.pone.0243057