Factors Associated with the Quality and Transparency of National Guidelines: A Mixed-Methods Study.

We assessed the methodological quality and transparency of all the national clinical practice guidelines that were published in Croatia up until 2017 and explored the factors associated with their quality rating. An in-depth quantitative and qualitative analysis was performed using rigorous methodology. We evaluated the guidelines using a validated AGREE II instrument with four raters; we used multiple linear regressions to identify the predictors of quality; and two focus groups, including guideline developers, to further explore the guideline development process. The majority of the guidelines (N = 74) were developed by medical societies. The guidelines' quality was rated low: the median standardized AGREE II score was low, 36% (IQR 28-42), and so were the overall-assessments. The aspects of the guidelines that were rated best were the "clarity of presentation" and the "scope and purpose" (median ≥ 59%); however, the other four domains received very low scores (15-33%). Overall, the guideline quality did not improve over time. The guidelines that were developed by medical societies scored significantly worse than those developed by governmental, or unofficial working groups (12-43% per domain). In focus group discussions, inadequate methodology, a lack of implementation systems in place, a lack of awareness about editorial independence, and broader expertise/perspectives in working groups were identified as factors behind the low scores. The factors identified as affecting the quality of the national guidelines may help stakeholders who are developing interventions and education programs aimed at improving guideline quality worldwide.

Cathepsin K expression in melanoma is associated with metastases.

INTRODUCTION: Melanoma of the skin shows a tendency to metastasize via lymph or blood secreting matrix metalloproteinases and cathepsins, which enable penetration through the dermis. Cathepsin K acts in cytoplasm of atypical melanocytes and completely cleaves internalized collagen. MATERIALS AND METHODS: Expression of cathepsin K was analyzed immunohistochemically in 45 melanomas and correlated to morphological and clinical parameters. RESULTS: During six years follow up, 13 patients developed lymph node metastases and three of them distant metastases. Positive expression of cathepsin K was found in 19 cases. In univariate regression analysis histological type, pagetoid spread, mitotic activity and cathepsin K expression were significantly connected to metastases. Cathepsin K was significantly associated to histologic type, ulceration, pagetoid spread and mitotic rate. In multiple logistic regression adjusted to these variables, cathepsin K was an independent predictor in occurrence of metastases (P=0.015). Median to the occurrence of metastases was 40 months in patients with cathepsin K positive expression and 71 months in patients with cathepsin K negative expression (P<0.001). CONCLUSIONS: In this preliminary study positive expression of cathepsin K in melanoma of the skin is associated with other unfavorable prognostic factors. We consider cathepsin K expression in primary tumor would significantly precipitate occurrence of metastases.