Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes.

BACKGROUND: HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes. METHODS: A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses. RESULTS: Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates. CONCLUSIONS: While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.

The Need to Implement Health Technology Assessment in Polish Hospitals-A Survey of 50 Hospital Managers.

Hospital-based health technology assessment (HB-HTA) is a scientific approach to inform decisions on investments in health technologies across multiple medical specialties at a hospital level. HB-HTA is not currently practiced in Poland. This study aimed to assess the need for HTA in Polish hospitals, including perceived benefits and challenges of adoption of HB-HTA in Poland, expected demand for training in HB-HTA, and perception of incentives to foster HB-HTA adoption. Study data were gathered using the computer-assisted telephone interview (CATI) technique. Between June and August 2021, 50 interviews were conducted: 52% of respondents had over 10 years of experience, and 40% comprised the highest degree reference hospitals. A high or moderate need for HB-HTA was reported by 86% of managers. The ability to indicate valuable and affordable medical technologies was the main reported benefit of HB-HTA (90%). The main obstacle to the adoption of HB-HTA was the shortage of competent staff (84%). The most important incentives to adopt HB-HTA were free training and premium financing from the National Health Fund. There is a clear need for HB-HTA in Polish hospitals despite some important obstacles.

Recommendations for the Implementation of Hospital Based HTA in Poland: Lessons Learned From International Experience.

Introduction: The main challenge of modern hospitals is purchasing medical technologies. Hospital-based health technology assessments (HB-HTAs) are used in healthcare facilities around the world to support management boards in providing relevant technologies for patients. Aim: This study was undertaken to update the existing body of knowledge on the characteristics of HB-HTA systems/models in the selected European countries. Insights gained from this study were used to provide an optimal approach for implementing HB-HTA in Poland. Materials and methods: Firstly, we carried out a systematic review in PubMed and embase. Secondly, we searched for gray literature via the AdHopHTA online handbook and the design book of the AdHopHTA project, as well as literature describing healthcare systems provided by the WHO. Then, we conducted in-depth interviews with HB-HTA experts from four countries. Finally, we selected ten countries from Europe and prepared frameworks for data collection and analyses. Results: The selected countries (Switzerland, Spain, France, Italy, Denmark, Finland, Sweden, the Netherlands, and Austria) are examples of decentralized or deconcentrated healthcare systems. In terms of HB-HTA, differences in organisational models (independent group, stand-alone, integrated-essential, integrated-specialised), type of financing (internally vs. externally), collaboration with an HTA National Agency and other stakeholders (e.g., Patients' Associations) were identified. HB-HTA engages multi-skilled staff with various academic backgrounds and operates mainly on a voluntary basis. Conclusion: Strengths and weaknesses associated with various organisational models must be carefully considered in the context of support for decentralized or centralized models of implementation while embarking on HTA activities in Polish hospitals.

Towards a more transparent HTA process in Poland: new Polish HTA methodological guidelines.

Introduction: Health technology assessment (HTA) in Poland supports reimbursement decisions via the Polish HTA Agency (AOTMiT), whose guidelines were updated in 2016. Methods: We identified key changes introduced by the update and, before guideline publication, analysed discrepancies between AOTMiT assessments and the submitting marketing authorisation holders (MAHs) to elucidate the context of the update. We compared the clarity and detail of the new guidelines versus those of the UK's National Institute for Health and Care Excellence (NICE). Results: The update specified more precise requirements for items such as indirect comparison or input data for economic modelling. Agency-MAH discrepancies relating to the subjects of the HTA update were found in 14.6% of published documents. The new Polish HTA guidelines were as clear and detailed as NICE's on topics such as assessing quality of evidence and economic modelling, but were less informative when describing (for example) pairwise meta-analysis. Conclusions: The Polish HTA guidelines update demonstrates lessons learned from internal and external experiences. The new guidelines adhere more closely to UK HTA standards, being clearer and more informative. While the update is expected to reduce Agency-MAH discrepancies, there remain areas for development, such as providing templates to aid HTA submissions.

GUIDING PRINCIPLES FOR GOOD PRACTICES IN HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT UNITS.

OBJECTIVES: Health technology assessment (HTA) carried out for policy decision making has well-established principles unlike hospital-based HTA (HB-HTA), which differs from the former in the context characteristics and ways of operation. This study proposes principles for good practices in HB-HTA units. METHODS: A framework for good practice criteria was built inspired by the EFQM excellence business model and information from six literature reviews, 107 face-to-face interviews, forty case studies, large-scale survey, focus group, Delphi survey, as well as local and international validation. In total, 385 people from twenty countries have participated in defining the principles for good practices in HB-HTA units. RESULTS: Fifteen guiding principles for good practices in HB-HTA units are grouped in four dimensions. Dimension 1 deals with principles of the assessment process aimed at providing contextualized information for hospital decision makers. Dimension 2 describes leadership, strategy and partnerships of HB-HTA units which govern and facilitate the assessment process. Dimension 3 focuses on adequate resources that ensure the operation of HB-HTA units. Dimension 4 deals with measuring the short- and long-term impact of the overall performance of HB-HTA units. Finally, nine core guiding principles were selected as essential requirements for HB-HTA units based on the expertise of the HB-HTA units participating in the project. CONCLUSIONS: Guiding principles for good practices set up a benchmark for HB-HTA because they represent the ideal performance of HB-HTA units; nevertheless, when performing HTA at hospital level, context also matters; therefore, they should be adapted to ensure their applicability in the local context.

Detection of contact allergy: using more extensive test series increases the diagnostic efficacy of patch tests.

BACKGROUND: Contact allergy is the most frequent type of allergy, affecting 26-40% of all adults and 21-36% children. The gold standard in the diagnosis of contact allergy is patch test. OBJECTIVE: To study the influence of the range and composition of patch test series on the efficacy of the diagnostic procedure. MATERIAL AND METHODS: Retrospective analysis of the frequency of positive reactions among patients diagnosed with patch tests at our Department during 2 periods: From December 2003 to March 2005, patients were tested with a series of 9 substances plus white petrolatum as the negative control. From April 2005 to July 2008, the series was expanded to 21 substances, while petrolatum was removed. RESULTS: In the analyzed period, 1379 patients were tested with 9 substances plus petrolatum (group referred to as "G9") and 682 patients with 21 substances ("G21"). In G9, at least one positive reaction was observed in 343 (24.9%, 95% CI: 22.6-27.2%) patients, as compared to 376 (55.1%; 95% CI: 51.4-58.7%) in G21 (p < 0.0001). The increase in the number of tested substances from 9 to 21 led to significant increase in the mean number of positive reactions per one patient (0.34 in G9 versus 0.90 in G21; p < 0.0001). We have not observed any positive reaction to white petrolatum. CONCLUSIONS: Patch testing with more extensive test series increases the chance for the detection of patient's sensitizations. As we have not observed any positive reaction to white petrolatum, using the vehicle as negative control does not seem to offer any advantage.

[Vitamin D3 in prevention of diseases in adults--a systematic review]. / Witamina D3 w prewencji chorób u doroslych--przeglad systematyczny.

INTRODUCTION: Current evidence indicates that vitamin D3 plays significant role in calcium balance and bone metabolism through lifetime. There are also evidence on preventive efficacy of vitamin D3 in diabetes, insulin-resistance, hypertension and malignancy. MATERIAL AND METHODS: The aim of the systematic review was to gather evidence regarding vitamin D3 in prevention of diseases in adults. MEDLINE via Pubmed was searched using key words: "vitamin D3, "prevention", "adults", "cardiovascular diseases", cancer", "osteoporosis", "common cold", "cold", "diabetes", "obesity", "depression". 26 trials were included into analysis: 17 randomized clinical trials, five observational studies, two systematic reviews, and two metaanalysis. RESULTS: Vitamin D3 appears to has beneficial effect in depression therapy, protective effect on beta-cells in diabetic patients and reducing frequency of adverse events such as thrombosis in patients with prostate cancer. Supplementing with vitamin D3 results with no significant improve in reducing body weight, fat, blood pressure, risk of hypertension, level of lipids in serum, response to treatment in cancer prostate (together with dexamethasone and carboplatin). Many studies highlights beneficial influence of vitamin D3 with calcium on bone mineral density in whole body. Another studies show improve in bone mineral density in hips and pelvic bones only. There were inconsistencies of studies results regarding role of vitamin D3 in prevention of diabetes, risk of breast cancer and influence on bone mineral density. CONCLUSIONS: Despite all inconsistencies supplementation of vitamin D3 is important and plays role in effective osteoporotic management and there is evidence on preventive efficacy of vitamin D3 in different diseases.