The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers

Introduction: Ulcers as a result of diabetes mellitus are a serious problem with an enormous impact on the overall global disease burden due to the increasing prevalence of diabetes. Because of long hospital stays, rehabilitation, often required home care and the use of social services diabetic foot complications are costly. Therapy with growth factors could be an effective and innovative add-on to standard wound care. Research questions: What is the benefit of therapies with growth factors alone or in combination with other technologies in the treatment of diabetic foot ulcer assessed regarding medical, economical, social, ethical and juridical aspects? Methods: We systematically searched relevant databases limited to English and German language and publications since 1990. Cost values were adjusted to the price level of 2008 and converted into Euro. A review and an assessment of the quality of publications were conducted following approved methodical standards conforming to evidence-based medicine and health economics. Results: We identified 25 studies (14 randomized controlled trials (RCT), nine cost-effectiveness analyses, two meta-analyses). The RCT compared an add-on therapy to standard wound care with standard wound care/placebo alone or extracellular wound matrix: in six studies becaplermin, in two rhEGF, in one bFGF, and in five studies the metabolically active skin grafts Dermagraft and Apligraf. The study duration ranged from twelve to 20 weeks and the study population included between 17 to 382 patients, average 130 patients. The treatment with becaplermin, rhEGF and skin implants Dermagraft and Apligraf showed in eight out of 13 studies an advantage concerning complete wound closure and the time to complete wound healing. Evidence for a benefit of treatment with bFGF could not be found. In four out of 14 studies the proportion of adverse events was 30% per study group with no difference between the treatment groups. The methodological quality of the studies was affected by significant deficiencies. The results showed becaplermin being cost-effective whereas no obvious statement can be made regarding Dermagraft and Apligraf because of diverging cost bases and incremental cost-effectiveness ratios. Discussion: Differences in standard wound care are complicating the comparison of study results. Taking into consideration the small to very small sample sizes and other methodological flaws with high potential of bias, the validity of the results with regard to effectiveness and cost-effectiveness has to be considered limited. The duration of treatment and follow-up examinations is not long enough to assess the sustainability of the intervention and the surveillance of ulcer recurrences or treatment related adverse events like the development of malignancy. Conclusions: There are indications of an advantage for the add-on therapy with growth factors in diabetic foot ulcers concerning complete wound closure and the time to complete wound healing. Further more studies of high methodological quality with adequate sample sizes and sufficient follow-up periods are necessary also investigating patient-relevant parameters like the health-related quality of life, the acceptance and tolerance of the intervention in addition to clinical outcomes

The statistical analysis of a clinical trial when a protocol amendment changed the inclusion criteria

Abstract Background Sometimes, protocol amendments that change the inclusion and exclusion criteria are required in clinical trials. Then, the patient populations before and after the amendment may differ. Methods We propose to perform separate statistical tests for the different phases, i.e. for the patients recruited before and after the amendment, and to combine the tests using Fisher's combination test. After a significant combination test a multiple testing procedure can be applied to identify the phase(s) to which a proof of efficacy refers. We assume that the amendment(s) are not based on any type of unblinded data. The proposed method is investigated within a simulation study. Results The proposed combination approach is superior to the 'naïve' strategy to ignore the differences between the phases and pooling the data to perform just one statistical test. This superiority disappears when there are hardly any differences between the two phases. Conclusion When one or more protocol amendments change the inclusion and exclusion criteria, one should realize that the populations may differ. In this case, separate tests for the different phases together with a combination test are a powerful method that can be applied in a variety of settings. The (first) amendment should specify the combination test to be applied in order to combine the different phases.</p

German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC

Developing search strategies for clinical practice guidelines in SUMSearch and Google Scholar and assessing their retrieval performance

<p>Abstract</p> <p>Background</p> <p>Information overload, increasing time constraints, and inappropriate search strategies complicate the detection of clinical practice guidelines (CPGs). The aim of this study was to provide clinicians with recommendations for search strategies to efficiently identify relevant CPGs in SUMSearch and Google Scholar.</p> <p>Methods</p> <p>We compared the retrieval efficiency (retrieval performance) of search strategies to identify CPGs in SUMSearch and Google Scholar. For this purpose, a two-term GLAD (GuideLine And Disease) strategy was developed, combining a defined CPG term with a specific disease term (MeSH term). We used three different CPG terms and nine MeSH terms for nine selected diseases to identify the most efficient GLAD strategy for each search engine. The retrievals for the nine diseases were pooled. To compare GLAD strategies, we used a manual review of all retrievals as a reference standard. The CPGs detected had to fulfil predefined criteria, e.g., the inclusion of therapeutic recommendations. Retrieval performance was evaluated by calculating so-called diagnostic parameters (sensitivity, specificity, and "Number Needed to Read" [NNR]) for search strategies.</p> <p>Results</p> <p>The search yielded a total of 2830 retrievals; 987 (34.9%) in Google Scholar and 1843 (65.1%) in SUMSearch. Altogether, we found 119 unique and relevant guidelines for nine diseases (reference standard). Overall, the GLAD strategies showed a better retrieval performance in SUMSearch than in Google Scholar. The performance pattern between search engines was similar: search strategies including the term "guideline" yielded the highest sensitivity (SUMSearch: 81.5%; Google Scholar: 31.9%), and search strategies including the term "practice guideline" yielded the highest specificity (SUMSearch: 89.5%; Google Scholar: 95.7%), and the lowest NNR (SUMSearch: 7.0; Google Scholar: 9.3).</p> <p>Conclusion</p> <p>SUMSearch is a useful tool to swiftly gain an overview of available CPGs. Its retrieval performance is superior to that of Google Scholar, where a search is more time consuming, as substantially more retrievals have to be reviewed to detect one relevant CPG. In both search engines, the CPG term "guideline" should be used to obtain a comprehensive overview of CPGs, and the term "practice guideline" should be used if a less time consuming approach for the detection of CPGs is desired.</p