Dataset Information

Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis.

ABSTRACT:

Background

Actinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (>?12 months) efficacy of interventions for AK.

Methods

To identify relevant studies, we will perform a systematic literature research in MEDLINE, Embase, and CENTRAL and hand-search pertinent trial registers. Two authors will independently screen titles and abstracts for eligibility. We will include RCTs with an inter-individual (parallel arm) design. The study population includes patients with a clinical or histopathologic diagnosis of AK. Eligibility will be restricted to the following interventions: surgical approaches, cryosurgery, ablative laser treatment, topical drug treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, or photodynamic therapy. As outcomes, we will consider the following endpoints: (1) the participant complete clearance rate, (2) the participant partial clearance rate, (3) the lesion-specific clearance, (4) the mean lesion reduction per patient, and (5) the number of withdrawals due to adverse events after at least 12 months after the end of treatment. Monotherapy or placebo will serve as a comparison. Estimates of effects from individual studies will be pooled using a random-effects model. Heterogeneity will be evaluated based on I² and chi-square test. The risk of bias will be estimated with the Cochrane Risk of Bias Tool by two review authors independently. The quality of evidence of the outcomes will be assessed with the GRADE approach. A network meta-analysis will be performed to combine direct and indirect evidence from the included RCTs.

Discussion

The potential of interventions to achieve a sustained clearance of AK has not been assessed to date. To investigate the long-term efficacy of interventions is important as the natural disease course is highly variable and relapses occur frequently even after initial lesion clearance. This review will help to set a framework for clinical decision making in patients with AK.

Systematic review registration

CRD42018095903 (PROSPERO).

SUBMITTER: Steeb T

PROVIDER: S-EPMC6788027 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis.

Steeb Theresa T Heppt Markus V MV Becker Lars L Kohl Christoph C French Lars E LE Berking Carola C

Systematic reviews 20191011 1

<h4>Background</h4>Actinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (> 12 months) efficacy of interventions for AK.<h4>Methods</h4>To identify relevant studies, we will perform a systematic literature research i ...[more]

PMID: 31604446

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Project description:Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the 'field'. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.

Project description:BackgroundMany treatments are currently available for amblyopic patients; although, the comparative efficacy of these therapies is unclear. We conducted a systematic review and network meta-analysis (NMA) to establish the relative efficacy of these treatments for amblyopia.MethodsElectronic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched from inception to Sep. 2019. Only Randomized clinical trials comparing any two or three of the following treatments were included: refractive correction (spectacles alone), patching of 2 h per day (patch 2H), patch 6H, patch 12H, patch 2H + near activities (N), patch 2H + distant activities (D), atropine (Atr) daily, Atr weekly, Atr weekly + plano lens over the sound eye (Plano), optical penalization and binocular therapy. The reviewers independently extracted the data according to the PRISMA guidelines; assessed study quality by Cochrane risk-of-bias tool for randomized trials. The primary outcome measure was the change in best-corrected visual acuity (BCVA) expressed as log MAR lines. Direct comparisons and a Bayesian meta-analysis were performed to synthesize data.ResultsTwenty-three studies with 3279 patients were included. In the network meta-analysis, optical penalization was the least effective of all the treatments for the change of visual acuity, spectacles (mean difference [MD], 2.9 Log MAR lines; 95% credibility interval [CrI], 1.8-4.0), patch 2H (MD, 3.3; 95% CrI, 2.3-4.3), patch 6H (MD, 3.6; 95% CrI, 2.6-4.6), patch 12H (MD, 3.4; 95% CrI, 2.3-4.5), patch 2H + N (MD, 3.7; 95% CrI, 2.5-5.0), patch 2H + D (MD, 3.5; 95% CrI, 2.1-5.0), Atr daily (MD, 3.2; 95% CrI, 2.2-4.3), Atr weekly (MD, 3.2; 95% CrI, 2.2-4.3), Atr weekly + Plano (MD, 3.7; 95% CrI, 2.7-4.7), binocular therapy (MD, 3.1; 95% CrI, 2.0-4.2). The patch 6H and patch 2H + N were better than spectacles ([MD, 0.73; 95% Crl, 0.10-1.40]; [MD, 0.84; 95% CrI, 0.19-1.50]).ConclusionsThe NMA indicated that the efficacy of the most of the examined treatment modalities for amblyopia were comparable, with no significant difference. Further high quality randomized controlled trials are required to determine their efficacy and acceptability.Systematic review registrationCRD42019119843.

Project description:BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.Prospero registration numberCRD42017073375.

Project description:Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.

Project description:ImportanceActinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending.ObjectiveTo evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors.Design, setting, and participantsThis retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used.Main outcomes and measuresAnnual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area).ResultsOverall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80.Conclusions and relevanceThere is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as age, sex, or comorbidities. The annual cost for 10 common conditions from Medicare had lower Q5:Q1 ratios that ranged from 1.33 (joint degeneration of back/neck) to 1.69 (chronic sinusitis) when compared with 1.72 to 1.80 for AKs. This suggests an opportunity to investigate and improve the value of health care delivery in the management of AKs.

Project description:Background: Medication non-adherence has a dynamic, temporal and multifactorial nature with a significant impact on economic and clinical outcomes. Interventions to improve adherence are complex and require adaptation to patients' needs, which may include patient's medical conditions. The aim of this study was to assess the comparative effectiveness of medication adherence interventions per type of clinical condition on adult patients. Methods: A systematic review with network meta-analysis was performed (PROSPERO registration number of CRD42018054598). An initial Pubmed search was conducted to select meta-analyses reporting results of interventions aiming to improve medication adherence. Primary studies were selected and those reporting results with a long-term follow up (?10 months) on adult patients were included for data extraction. Study characteristics, description of interventions and adherence outcomes were extracted. Adherence interventions were classified in four groups: educational, attitudinal, technical, and rewards. Clinical conditions were classified in four groups: circulatory system and metabolic diseases, infectious diseases, musculoskeletal diseases, and mental, behavioral or neurodevelopmental disorders. Network meta-analyses with effect sizes expressed as odds ratio (OR) with a 95% credibility interval (CrI) were built. Ranking probabilities for each measure of adherence were calculated by using surface under the cumulative ranking analysis (SUCRA). Results: A total of 61 meta-analysis and 149 primary studies were included in the qualitative synthesis and 80 primary studies in the quantitative analysis. The most effective interventions were: educational + technical 79.6% [OR: 0.44 (CrI: 0.26, 0.73)] and 73.3% [OR: 0.56 (0.36, 0.84)] in circulatory system and metabolic diseases and infectious diseases respectively. Attitudinal intervention had the greatest probability for musculoskeletal diseases of 92.3% in SUCRA [OR: 0.30 (0.10, 0.86)]. Finally, educational + attitudinal interventions had the greatest effect (SUCRA 73.8%) for mental, behavioral or neurodevelopmental disorders, although this was not significant according to consistency analysis. Conclusion: Effectiveness of interventions seems to be related to the clinical condition. Educational and technical interventions resulted in a major effect on long-term management of medication adherence in patients with infectious diseases (HIV) and circulatory system and metabolic diseases whereas attitudinal components presented a higher effect on musculoskeletal and mental, behavioral or neurodevelopmental disorders.

Dataset Information

Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis.

Background

Methods

Discussion

Systematic review registration

Publications

Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis.

Similar Datasets

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