Background: The HEcoPerMed consortium developed a methodological guidance for the harmonization and improvement of economic evaluations in personalized medicine. Materials & methods: In three therapeutic areas, health economic models were developed to scrutinize the recommendations of the guidance. Results: Altogether, 20 of the 23 recommendations of the guidance were addressed by the models. Seven recommendations were applied in all studies, six in two of the studies and seven in one of the studies. Recommendations with an essential role on the final conclusions of the analyses were identified in each study. Conclusion: The guidance was found to be best used as a tool to identify and prioritize issues, verify solutions and justify decisions during the economic analysis of personalized interventions.

In this paper, we present a complete and efficient solution of guidance, navigation and control for a quadrotor platform to accomplish 3D coverage flight missions in mapped vineyard terrains. Firstly, an occupancy grid map of the terrain is used to generate a safe guiding coverage path using an Iterative Structured Orientation planning algorithm. Secondly, way-points are extracted from the generated path and added to them trajectory\'s velocities and accelerations constraints. The constrained way-points are fed into a Linear Quadratic Regulator algorithm so as to generate global minimum snap optimal trajectory while satisfying both the pointing and the corridor constraints. Then, when facing unexpected obstacles, the quadrotor tends to re-plan its path in real-time locally using an Improved Artificial Potential Field algorithm. Finally, a geometric trajectory tracking controller is developed on the Special Euclidean group SE(3). The aim of this controller is to track the generated trajectory while pointing towards predetermined direction using the vector measurements provided by the inertial unit. The performance of the proposed method is demonstrated through several simulation results. In particular, safe guiding paths are achieved. Obstacle-free optimal trajectories that satisfy the way-point position, the pointing direction, and the corridor constraints, are successfully generated with optimized platform snap. Besides, the implemented geometric controller can achieve higher trajectory tracking accuracy with an absolute value of the maximum error in the order of 10-3 m.

Background: Venous thromboembolism (VTE) is a rare side effect of hormonal therapy in transgender persons. Prothrombotic genetic variants can increase this risk. For this reason, previous VTE and/or genetic thrombophilia may be considered by some as contraindications to hormonal treatment. Aim: To formulate directions for clinical practice about the indications for thrombophilia screening and when to consider combination therapy of therapeutic anticoagulation and hormonal treatment as a safe alternative to withholding hormonal treatment. Methods: We conducted a literature search and describe a case series. All adult patients with gender dysphoria and a known prothrombotic genetic variant or history of VTE were invited by letter to participate in this study. Results: In our center, thrombophilia screening before start of hormonal treatment was restricted to those with a personal or family history of VTE. Sixteen individuals with a history of VTE and/or an underlying prothrombogenic condition were described. The time of follow up varied from 4 months to 20 years. Seven trans women had a positive thrombophilia screening (2 Factor V Leiden (FVL), 1 FVL + anticardiolipin antibodies, 1 FVL + high Factor VIII coagulant activity, 1 protein C deficiency, 1 prothrombin mutation, 1 positive lupus anticoagulant). Three trans women experienced an unprovoked VTE after start of hormonal therapy of which one lead to a positive thrombophilia screening. One VTE event in a trans woman was assumed to be provoked by surgery. Five trans men were identified with a prothrombogenic mutation (3 FVL, 1 protein C deficiency, 1 prothrombin mutation). One trans man, with a negative thrombophilia screen, experienced multiple provoked VTE events before start of hormonal therapy. Conclusion: Based on our literature review and case series we offer guidance when confronted with patients with previous VTE and/or genetic thrombophilia requesting hormonal interventions.

To develop a digital communication tool to improve the implementation of up-to-date COVID-19 recommendations. Specifically, to improve patient, caregiver and public understanding of healthcare recommendations on prevention, diagnoses and treatment.
Multi-stakeholder engagement design. In conjunction with the COVID-19 Recommendations and Gateway to Contextualization RecMap, we co-developed a stakeholder prioritization, drafting and editing process to enhance guideline communication and understanding.
This paper presents the multi-stakeholder development process with three distinct plain language recommendation formats: formal recommendation, good practice statement, and additional guidance. Our case study of COVID-19 plain language recommendations PLRs addresses both public health interventions (e.g., vaccination, face masks) and clinical interventions (e.g., home pulse oximetry).
This paper presents a novel approach to engaging stakeholders in improving the communication and understanding of published guidelines during the COVID-19 pandemic.

UNASSIGNED: Coronavirus disease 2019 (COVID-19) began in 2019 with several unknown factors. The World Health Organization (WHO) subsequently developed COVID-19 occupational safety and health (OSH) guidelines to reduce occupational COVID-19 transmission. Many countries also developed their own COVID-19 OSH guidelines, but whether these guidelines included WHO\'s guidelines and whether including WHO\'s guidelines in countries\' COVID-19 OSH guidelines reduced COVID-19 transmission is unknown.
UNASSIGNED: The objectives of our study were to (1) compare the COVID-19 OSH guidelines of several countries to WHO\'s OSH guidelines, (2) estimate associations between characteristics of countries and their OSH guidelines and the number of WHO\'s OSH guidelines included in countries\' OSH guidelines, and (3) estimate associations between WHO\'s OSH guidelines included in countries\' OSH guidelines and COVID-19 risk, death risk, and case-fatality proportion.
UNASSIGNED: This study represents international, ecological research of 36 countries from all six world health regions. Countries\' COVID-19 OSH guidelines were compared with WHO\'s OSH guidelines. Linear regression models adjusted for potential confounders were used to estimate associations of interest.
UNASSIGNED: The median number of WHO\'s 15 COVID-19 OSH guidelines included in countries\' COVID-19 OSH guidelines was eight. Countries\' COVID-19 OSH guidelines focused on workers included significantly more of WHO\'s COVID-19 OSH guidelines than countries\' COVID-19 OSH guidelines focused on general populations. Including \"provide personal protective equipment for workers\" and \"create workplace policy for wearing personal protective equipment\" in countries\' COVID-19 OSH guidelines were significantly related to decreased COVID-19 risk, death risk, and/or case-fatality proportion.
UNASSIGNED: Countries\' COVID-19 OSH guidelines should include WHO\'s guidelines, focus on workers, and include \"provide personal protective equipment for workers\" and \"create workplace policy for wearing personal protective equipment.\"

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) has become a mature and mainstream minimally invasive surgical technique for treating lumbar disc herniation (LDH). Repeated fluoroscopy, with more than 30 shots on average, is inevitable to ensure its accuracy and safety. However, exposure to X-rays may pose a threat to human health. We herein report a case of ultrasound (US)-assisted PELD in two levels of LDH to explore a new possibility that can reduce the radiation dose during puncture and cannulation in PELD.
METHODS: A 38-year-old man with low back pain and left leg pain for more than 7 years came to our clinic, his symptoms had aggravated for 1 month, and he was diagnosed with L3-4 and L4-5 disc herniations. He received US-guided PELD with good results: His straight leg elevation increased from 40 to 90 degrees after PELD, and his visual analog scale (VAS) and Oswestry Disability Index scores both significantly decreased immediately and 6 mo after PELD. With the guidance of US, he received only two shots of fluoroscopy (fluoroscopic time: 4.4 s; radiation dose: 3.98 mGy). To our knowledge, this is the first case of US-guided puncture and cannulation of PELD for LDH at two levels.
CONCLUSIONS: US could be used to guide PELD and has the potential to largely reduce radiation than traditional X-ray guidance.

BACKGROUND: The footprint of drug distribution is multinational, but the regulatory frameworks supporting drug development, review, and approval remain largely regional. As a result, industry faces regulatory standards that may be complementary, additive, or contradictory, resulting in global regulatory dissonance (GRD).
METHODS: Global regulatory dissonance was explored through a case study of drug development (postmenopausal osteoporosis) using survey methodology.
RESULTS: In the feedback received, respondents generally agreed that GRD increases the complexity, timelines, and size of registration studies. Dissonant regulatory feedback on proposed labeling, applications, and benefit-risk assessments was also reported. Multiple causes of GRD were identified, including dissonant drug regulatory authority advice, guidelines, benefit-risk assessments, drug approval precedents, medical standards of care, and health technology assessments. Harmonization of guidelines, scientific advice, benefit-risk procedures, and expanded use of mutual recognition agreements were identified as mechanisms thought to reduce GRD.
CONCLUSIONS: The results suggest that global access to new drugs may be enhanced through a greater understanding of GRD.

In the advanced medical field, there is a constant need for efficient guidance formulation by regulators. Technology forecasting as a surveillance for regulation needs may be an effective solution by notifying regulatory authorities of the possible future changes in regulations. However, the lack of tangible frameworks has made the relationship between technology forecasting and regulation difficult to comprehend, and has led to an under-analyzed state of how technology forecasts are implemented into the guidance formulation process. In this study, we introduce a framework built specifically for facilitating the comprehension of the relationship between technologies enlisted in technology forecasting and guidances formulated after the forecasting, and applied the framework to a case of technology forecasting conducted by regulatory authorities in Japan. Four patterns of the relationships between a technology forecasting conducted by regulators and the guidances developed after the forecast are identified. The results and discussions provide suggestions of technology forecast design and application in the guidance formulation process by regulators in the field of medical devices.

BACKGROUND: Global guidance can help countries strengthen their health systems to deliver effective interventions to their populations. However, to have an impact, guidance needs to be contextualised or adapted to local settings; this process includes consideration of health system arrangements and political system factors. To date, methods to support contextualisation do not exist. In response, a workbook was designed to provide specific methods and strategies to enable the contextualisation of WHO\'s \'Optimizing health worker roles to improve maternal and newborn health\' (OptimizeMNH) guidance at the national or subnational level. The objective of this study was to describe the process of developing the workbook and identify key steps of the development process, barriers that arose and facilitators that helped overcome some of these barriers.
METHODS: A qualitative single case study design was carried out. Interviews, documents and a reflexive journal were used. Constant comparison and an edit-style of organisation were used during data analysis to develop concepts, themes, subthemes and relationships among them.
RESULTS: Thirteen interviews were conducted and 52 documents were reviewed. Three main steps were identified in the process of developing the workbook for health systems guidance contextualisation, namely (1) determining the need for and gaining approval to develop the workbook, (2) developing the workbook (taking on the task, creating the structure of the workbook, operationalising its components, undergoing approval processes and editing it), and (3) implementing the workbook both at the WHO level and at the national/subnational level. Five barriers and/or facilitators emerged relevant to each step, namely (1) having well-placed and credible champions, (2) creating and capitalising on opportunities, (3) finding the right language to engage various actors and obtain buy-in, (4) obtaining and maintaining meaningful buy-in, and (5) ensuring access to resources.
CONCLUSIONS: Understanding the key steps and the critical factors involved in the process of developing the workbook could help in the planning of similar and other tools aimed to support the implementation of WHO guidance. A plan for dissemination and implementation needs to be addressed during the preparation of these tools.

Vaccination in pregnancy is an effective strategy to prevent serious infections in mothers and their infants. Safety of this strategy is of principal importance to all stakeholders. As the number of studies assessing safety of vaccines in pregnancy increases, the need to ensure consistent collection and reporting of critical data to allow comparisons and data pooling becomes more important. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project aims to improve data collection and create a shared understanding of maternal, fetal and neonatal outcomes in order to progress the global agenda for vaccination in pregnancy. The guidance in this document has been developed to harmonize the data collected in case report forms used for safety monitoring in clinical trials of vaccination in pregnant women. Data to be collected is prioritized to allow applicability in diverse research settings, including low and middle-income countries. Standardized data will enable the research community to have a common base upon which to conduct meta-analyses, strengthening the applicability of outcomes to different settings.