A Critical Appraisal of Evidence- and Consensus-Based Guidelines for Actinic Keratosis.
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ABSTRACT:
SUBMITTER: Wessely A
PROVIDER: S-EPMC7985770 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
A Critical Appraisal of Evidence- and Consensus-Based Guidelines for Actinic Keratosis.
Wessely Anja A Steeb Theresa T Heppt Franz F Hornung Annkathrin A Kaufmann Matthias D MD Koch Elias A T EAT Toussaint Frédéric F Erdmann Michael M Berking Carola C Heppt Markus V MV
Current oncology (Toronto, Ont.) 20210219 1
Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently available guidelines for AK. Guidelines published within the last 5 years were identified in a systematic search of guideline databases, Medline and Embas ...[more]
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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.
| S-EPMC4065271 | biostudies-literature
Project description:Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions. We demonstrate in 37 AKs from both immunosuppressed and immunocompetent patients that there are significant similarities between AKs and cSCC in terms of mutational burden, copy number alterations, mutational signatures, and patterns of driver gene mutations. We identify 44 significantly mutated AK driver genes and confirm that these genes are similarly altered in cSCC. We identify azathioprine mutational signature in all AKs from patients exposed to the drug, providing further evidence for its role in keratinocyte carcinogenesis. cSCCs differ from AKs in having higher levels of intrasample heterogeneity. Alterations in signaling pathways also differ, with immune-related signaling and TGFβ signaling significantly more mutated in cSCC. Integrating our findings with independent gene expression datasets confirms that dysregulated TGFβ signaling may represent an important event in AK‒cSCC progression.
| S-EPMC8221374 | biostudies-literature
Project description:BackgroundDual antiplatelet therapy (DAPT) in the form of aspirin plus a P2 Y12 inhibitor, when indicated, is one of the key treatments in coronary artery disease (CAD). Many recommendations on DAPT in patients with CAD based on current guidelines are largely inconsistent. In our current study, we aimed at systematically reviewing DAPT-relevant clinical practice guidelines, and highlighting their commonalities and differences for better informed decision-making.MethodsContemporary guidelines in English were searched in MEDLINE, Embase and websites of guideline organizations and professional societies. Guidelines with recommendations on DAPT for CAD patients were included. Guideline quality was appraised with the 6-domain Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. The reporting of conflicts of interest (COI) was assessed individually with supplementary items from the RIGHT (Reporting Item for Practice Guidelines in Healthcare) checklist. Meanwhile, extraction of recommendations was performed.ResultsA total of 18 guidelines fulfilled our inclusion criteria. Most of them were graded with relatively good scores averaging from 42% to 74%. Domains for lower scores were in "stakeholder involvement" and "application." The reporting of COI was satisfactory. For the recommendations on DAPT, most guidelines with high AGREE II scores included consistent recommendations on the timing and P2 Y12 inhibitor selection. Nonetheless, conflicts still exist on the duration of DAPT.ConclusionsQuality of guidelines for DAPT in CAD was relatively high, though defects existed in "Applicability" and "Stakeholder Involvement." As these guidelines developed, DAPT recommendations gradually converged on a consensus. Clinical decision should be made on an individual basis.
| S-EPMC6906997 | biostudies-literature
Project description:OBJECTIVES: Standards for evaluating evidence-based medicine (EBM) point-of-care (POC) summaries of research are lacking. The authors developed a "Critical Appraisal for Summaries of Evidence" (CASE) worksheet to help assess the evidence in these tools. The authors then evaluated the reliability of the worksheet. METHODS: The CASE worksheet was developed with 10 questions covering specificity, authorship, reviewers, methods, grading, clarity, citations, currency, bias, and relevancy. Two reviewers independently assessed a random selection of 384 EBM POC summaries using the worksheet. The responses of the raters were then compared using a kappa score. RESULTS: The kappa statistic demonstrated an overall moderate agreement (??=?0.44) between the reviewers using the CASE worksheet for the 384 summaries. The 3 categories of evaluation questions in which the reviewers disagreed most often were citations (??=? 0), bias (??=?0.11), and currency (??=?-0.18). CONCLUSIONS: The CASE worksheet provided an effective checklist for critically analyzing a treatment summary. While the reviewers agreed on worksheet responses for most questions, variation occurred in how the raters navigated the tool and interpreted some of the questions. Further validation of the form by other groups of users should be investigated.
| S-EPMC3738079 | biostudies-other
Project description:Background Tobacco use is a leading preventable cause of morbidity and mortality globally. Clinical practice guidelines for the treatment of tobacco use dependence are of varied scope and quality, making it challenging for users to select and apply recommendations. Objective The study objective is to identify and critically appraise the quality of existing clinical practice guidelines for tobacco cessation. Setting The study occurred between collaborative academic institutions located in Qatar and New Zealand. Methods A systematic literature search was performed for the period 2006-2018 through the following databases: PubMed, EMBASE, CINAHL, ISI Web of Science, Scopus, National Guideline Clearing House, Campbell Library, Health System Evidence, Joanna Briggs Institute Evidence-Based Practice Database, Academic Search Complete, ProQuest, PROSPERO, and Google Scholar. Relevant professional societies' and health agencies' websites were also searched. Two reviewers independently extracted and assessed guidelines' quality using Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Main outcome measure Standardized domain scores according to the AGREE II instrument. Results 7741 hits were identified. After removing duplicates and screening, 24 guidelines were included. Highest guideline quality was for National Institute for Health and Care Excellence (NICE) guideline with an overall ranking score of 87.56% and least quality was for Japanese Circulation Society Joint Working Group with an overall score of 29.34%. Domain 4 of AGREE II (clarity of presentation) had the highest average quality score (70.95%), while the lowest average quality scores were for Domain 2 (Rigour of Development) (50.21%) and Domain 5 (Applicability) (45.05%). Conclusion Seven guidelines were judged to be of high quality (overall score of ≥ 70%). Future guidelines for tobacco dependence treatment should use rigorous methods of development and provide applicable recommendations.
| S-EPMC7878272 | biostudies-literature
Project description:Actinic keratoses are pre-malignant skin lesions that require personalized care, a lack of which may result in poor treatment adherence and suboptimal outcomes. Current guidance on personalizing care is limited, notably in terms of tailoring treatment to individual patient priorities and goals and supporting shared decision-making between healthcare professionals and patients. The aim of the Personalizing Actinic Keratosis Treatment panel, comprised of 12 dermatologists, was to identify current unmet needs in care and, using a modified Delphi approach, develop recommendations to support personalized, long-term management of actinic keratoses lesions. Panellists generated recommendations by voting on consensus statements. Voting was blinded and consensus was defined as ≥ 75% voting 'agree' or 'strongly agree'. Statements that reached consensus were used to develop a clinical tool, of which, the goal was to improve understanding of disease chronicity, and the need for long-term, repeated treatment cycles. The tool highlights key decision stages across the patient journey and captures the panellist's ratings of treatment options for attributes prioritized by patients. The expert recommendations and the clinical tool can be used to facilitate patient-centric management of actinic keratoses in daily practice, encompassing patient priorities and goals to set realistic treatment expectations and improve care outcomes.
| S-EPMC10265500 | biostudies-literature
Project description:BackgroundClinical practice guidelines have become increasingly widely used to guide quality improvement of clinical practice. Qualitative research may be a useful way to improve the quality and implementation of guidelines. The methodology for qualitative evidence used in guidelines development is worthy of further research.MethodsA comprehensive search was made of WHO, NICE, SIGN, NGC, RNAO, PubMed, Embase, Web of Science, CNKI, Wanfang, CBM, and VIP from January 1, 2011 to February 25, 2020. Guidelines which met IOM criteria and were focused on clinical questions using qualitative research or qualitative evidence, were included. Four authors extracted significant information and entered this onto data extraction forms. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the guidelines' quality. The data were analyzed using SPSS version 17.0 and R version 3.3.2.ResultsSixty four guidelines were identified. The overall quality of the guidelines was high (almost over 60%). Domain 1 (Scope and Purpose) was ranked the highest with a median score of 83% (IQ 78-83). Domain 2 (Stakeholder involvement) and Domain 5 (Applicability) were ranked the lowest with median scores of 67% (IQ 67-78) and 67% (IQ 63-73) respectively. 20% guidelines used qualitative research to identify clinical questions. 86% guidelines used qualitative evidence to support recommendations (mainly based on primary studies, a few on qualitative evidence synthesis). 19% guidelines applied qualitative evidence when considering facilitators and barriers to recommendations' implementation. 52% guideline developers evaluated the quality of the primary qualitative research study using the CASP tool or NICE checklist for qualitative studies. No guidelines evaluated the quality of qualitative evidence synthesis to formulate recommendations. 17% guidelines presented the level of qualitative research using the grade criteria of evidence and recommendation in different forms such as I, III, IV, very low. 28% guidelines described the grades of the recommendations supported by qualitative and quantitative evidence. No guidelines described the grade of recommendations only supported by qualitative evidence.ConclusionsThe majority of the included guidelines were high-quality. Qualitative evidence was mainly used to identify clinical questions, support recommendations, and consider facilitators and barriers to implementation of recommendations'. However, more attention needs to be paid to the methodology. For example, no experts proficient in qualitative research were involved in guideline development groups, no assessment of the quality of qualitative evidence synthesis was included and there was lack of details reported on the level of qualitative evidence or grade of recommendations.
| S-EPMC7302150 | biostudies-literature
Project description:This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.
| S-EPMC10969398 | biostudies-literature
Project description:BackgroundActinic 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.ObjectivesHere 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.MethodsHuman and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.ResultsAn 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®.ConclusionThese 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.
| S-EPMC5491107 | biostudies-literature
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.
| S-EPMC5470414 | biostudies-literature