Daily sitting time and its association with non-communicable diseases and multimorbidity in Catalonia.

BACKGROUND: Non-communicable diseases (NCDs) account for 71% of deaths worldwide and individual behaviours such as sedentariness play an important role on their development and management. However, the detrimental effect of daily sitting on multiple NCDs has rarely been studied. This study sought (i) to investigate the association between sitting time and main NCDs and multimorbidity in the population of Catalonia and (ii) to explore the effect of physical activity as a modifier of the associations between sitting time and health outcomes. METHODS: Cross-sectional data from the 2016 National Health Survey of Catalonia were analyzed, and multivariable logistic regression, adjusting for socio-demographics and individual risk factors (tobacco and alcohol consumption, diet, hyperlipidaemia, hypertension, body mass index) was used to estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between sitting time and NCDs. RESULTS: A total of 3320 people ≥15 years old were included in the study. Sitting more than 5 h/day was associated with a higher risk of cardiovascular disease (OR 1.90, 95% CI: 1.21-2.97), respiratory disease (OR 1.61, 95% CI: 1.13-2.30) and multimorbidity (OR 2.80, 95% CI: 1.53-5.15). Sitting more than 3 h/day was also associated with a higher risk of multimorbidity (OR 2.26, 95% CI: 1.23-4.16). Physical activity did not modify the associations between sitting time and any of the outcomes. CONCLUSIONS: Daily sitting time might be an independent risk factor for some NCDs, such as cardiovascular disease, respiratory disease and multimorbidity, independently of the level risk of physical inactivity.

Sustaining Meaningful Patient Engagement Across the Lifecycle of Medicines: A Roadmap for Action.

BACKGROUND: There is increased recognition that incorporating patients' perspectives and insights into the medicines development process results in better health outcomes and benefits for all involved stakeholders. Despite the increased interest and the existence of frameworks and practical recommendations, patient engagement (PE) is not yet considered standard practice. The objective of this work was to provide a roadmap to support systematic change in all stakeholder organisations involved in medicines development across Europe, patients and patient organisations, medicines developers, academia, regulatory authorities, Health Technology Assessment bodies, payers, policy-makers and public research funders, to sustain PE practices. METHODS: A mixed-methods approach was used by the EU-funded Innovative Medicines Initiative PARADIGM Consortium to co-develop the sustainability roadmap including background work to identify success factors and scenarios for sustainable PE. The roadmap development was based on the Theory of Change concept and populated with findings from (1) interviews with national/ and international institutions with the potential to increase PE uptake by other stakeholders; (2) multi-stakeholder workshops and webinars; and (3) consultations with specific stakeholder groups, Consortium members and a consultative body formed by international PE initiatives. RESULTS: This roadmap sets strategic goals for the PE community to achieve meaningful and systematic PE through changes in the culture, processes and resources of stakeholder organisations. It brings in key PARADIGM outputs to work in a coordinated fashion with existing frameworks and mechanisms to achieve system-wide sustained PE. CONCLUSIONS: The roadmap provides a framework for all stakeholders to take collective action within their organisations and across Europe to implement PE in a sustainable manner.

Evaluation of patient engagement in medicine development: A multi-stakeholder framework with metrics.

BACKGROUND: Patient engagement is becoming more customary in medicine development. However, embedding it in organizational decision-making remains challenging, partly due to lack of agreement on its value and the means to evaluate it. The objective of this project was to develop a monitoring and evaluation framework, with metrics, to demonstrate impact and enhance learning. METHODS: A consortium of five patient groups, 15 biopharmaceutical companies and two academic groups iteratively created a framework in a multi-phase participatory process, including analysis of its application in 24 cases. RESULTS: The framework includes six components, with 87 metrics and 15 context factors distributed among (sub)components: (a) Input: expectations, preparations, resources, representativeness of stakeholders; (b) Activities/process: structure, management, interactions, satisfaction; (c) Learnings and changes; (d) Impacts: research relevance, study ethics and inclusiveness, study quality and efficiency, quality of evidence and uptake of products, empowerment, reputation and trust, embedding of patient engagement; (e) Context: policy, institutional, community, decision-making contextual factors. Case study findings show a wide variation in use of metrics. There is no 'one size fits all' set of metrics appropriate for every initiative or organization. Presented sample sets of metrics can be tailored to individual situations. CONCLUSION: Introducing change into any process is best done when the value of that change is clear. This framework allows participants to select what metrics they value and assess to what extent patient engagement has contributed. PATIENT CONTRIBUTION: Five patient groups were involved in all phases of the study (design, conduct, interpretation of data) and in writing the manuscript.

Understanding multi-stakeholder needs, preferences and expectations to define effective practices and processes of patient engagement in medicine development: A mixed-methods study.

BACKGROUND: The holistic evolution of patient engagement in medicines development requires a more detailed understanding of the needs of all involved stakeholders, and one that better accounts for the specific needs of some potentially vulnerable patient populations and key stages in medicines development. OBJECTIVE: The purpose of this convergent mixed-methods study was to better understand the needs of different stakeholders concerning patient engagement at three key stages in medicines development: research priority setting, clinical trial design and early dialogues with Health Technology Assessment bodies and regulators. DESIGN: This study brought together findings from three sources: i) an online questionnaire, ii) face-to-face consultations with two potentially vulnerable patient populations, a workshop with Health Technology Assessment bodies, and iii) three-step modified Delphi methodology. RESULTS: Overall stakeholders still need additional varied support mechanisms to undertake, sustain or measure value of patient engagement. Health Technology Assessment bodies need better rationale for patient engagement in early dialogue and tools to support its implementation. Improved awareness and understanding of the need and value that involving patients, who are often considered as potentially vulnerable, can bring is needed, as is better accommodation of their specific needs. Similarly, weighted Delphi categories were as follows: aims and objectives, and sustainability. Several additional themes were common across the three key stages in medicines development. CONCLUSION: This broad-reaching study provides the blocks needed to build a framework for patient engagement in medicines development. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in review and interpretation of data.

Shaping Policy on Chronic Diseases through National Policy Dialogs in CHRODIS PLUS.

Policy dialogs are deliberative dialogue that gather policy makers and relevant stakeholders from across disciplines to discuss a topic of mutual interest. They typically serve as a single element in a broader policymaking cycle, either informing the content of new policy or forming a component of policy evaluation and review. In the joint action CHRODIS PLUS, national policy dialogs were conducted in fourteen EU Member States. The aim of the dialogs was to identify new policies or changes to existing policies and legislation that are capable of tackling major risk factors for chronic disease, to strengthen health promotion and prevention programs and to ensure health systems are equipped to respond to priority issues within the chronic diseases field. In this paper, we present the CHRODIS PLUS policy dialog methodology, as well as results and lessons learnt from three national policy dialogs held in Ireland, Portugal and Spain. After discussion of the results, we conclude that the CHRODIS PLUS methodology is an effective mechanism to provoke deliberative discussion around chronic disease prevention and management in different countries. However, it is essential to ensure adequate human and financial resources-as well as political commitment-to accomplish objectives set out during the policy dialogs. We argue that priority-setting across sectors can improve the resilience of health systems and opportunities for investment in Health in All Policies (HiAP), both at European Union and Member State levels.

Evaluating the "return on patient engagement initiatives" in medicines research and development: A literature review.

BACKGROUND: Showing how engagement adds value for all stakeholders can be an effective motivator for broader implementation of patient engagement. However, it is unclear what methods can best be used to evaluate patient engagement. This paper is focused on ways to evaluate patient engagement at three decision-making points in the medicines research and development process: research priority setting, clinical trial design and early dialogues with regulators and health technology assessment bodies. OBJECTIVE: Our aim was to review the literature on monitoring and evaluation of patient engagement, with a focus on indicators and methods. SEARCH STRATEGY AND INCLUSION CRITERIA: We undertook a scoping literature review using a systematic search, including academic and grey literature with a focus on evaluation approaches or outcomes associated with patient engagement. No date limits were applied other than a cut-off of publications after July 2018. DATA EXTRACTION AND SYNTHESIS: Data were extracted from 91 publications, coded and thematically analysed. MAIN RESULTS: A total of 18 benefits and 5 costs of patient engagement were identified, mapped with 28 possible indicators for their evaluation. Several quantitative and qualitative methods were found for the evaluation of benefits and costs of patient engagement. DISCUSSION AND CONCLUSIONS: Currently available indicators and methods are of some use in measuring impact but are not sufficient to understand the pathway to impact, nor whether interaction between researchers and patients leads to change. We suggest that the impacts of patient engagement can best be determined not by applying single indicators, but a coherent set of measures.

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS.

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.

Pharmaceutical trademarks: navigating through the FDA's pilot program.

Creation and clearance of pharmaceutical trademarks continues to be one of the most difficult and challenging areas of trademark law. The Food and Drug Administration (FDA) recently initiated a 2-year Pilot Program under Prescription Drug User Fee Act (PDUFA) IV. The intent of the program is to enable participating pharmaceutical firms to evaluate proposed pharmaceutical marks and submit the data generated from those evaluations to the FDA for review. Submitting a trademark to the FDA warrants questions: What supporting data is needed and accepted when proposing a mark? What issues might arise, and how can they be averted? In a recent Thomson Reuters on-demand webinar (http://science.thomsonreuters.com/news/2010-02/8580404/), a group of renowned experts in the field of trademark development review the FDA pilot program, outline the requirements for submission and discuss what the changes will mean in clearing new pharmaceutical marks. They also present various approaches to trademark development and evaluation in light of the FDA's views.

Tolvaptan for the treatment of hyponatremia and congestive heart failure.

Vasopressin plays a central role in regulating body fluid homeostasis, serum osmolality and vascular tone. In response to elevated serum osmolality, vasopressin acts on V2 renal receptors increasing water reabsorption and causing serum sodium to decrease. Pathological conditions characterized by abnormally elevated vasopressin levels such as heart failure (HF) or syndrome of inappropriate antidiuretic hormone (SIADH) can result in hyponatremia. Tolvaptan is a new selective nonpeptide vasopressin V2 receptor antagonist that has shown to rapidly normalize serum sodium concentrations in hyponatremic patients. In patients with congestive heart failure (CHF) and symptoms of volume overload, tolvaptan prompted rapid free water elimination and improved short-term signs and symptoms of HF, although no effect on long-term mortality or HF-related morbidity was observed. Data from phase III studies including over 5,000 patients have demonstrated that tolvaptan is a safe and well tolerated vasopressin receptor antagonist, whose long-term use is not associated with adverse outcomes. Tolvaptan has been recently approved for the treatment of hyponatremia and a marketing authorization application has been filed for the treatment of CHF.

Dabigatran etexilate in venous thromboembolism.

Dabigatran etexilate (Pradaxa) is the orally available prodrug of dabigatran, a potent compound belonging to the new class of nonpeptide direct thrombin inhibitors (DTIs). Following oral administration, dabigatran etexilate reached peak plasma concentrations within 2 hours, showed linear pharmacokinetics across a wide dose range, a linear relationship between ecarin clotting time (ECT) and international normalized ratio (INR), and no significant food or drug interactions. Dabigatran etexilate at once-daily doses of 150 mg and 220 mg has demonstrated non-inferiority to once-daily enoxaparin 40 mg for the prevention of venous thromboembolism (VTE) in patients undergoing total hip or knee replacement surgery in two large, randomized, double-blind clinical trials. The safety profile of dabigatran etexilate was similar to that of enoxaparin with comparable rates of major bleeding, liver enzyme elevation and acute coronary events. Oral availability of dabigatran etexilate, together with a rapid onset and offset of action and predictable anticoagulation response, makes this compound an attractive alternative to traditional anticoagulant therapies for the prevention of VTE.

Novelties in atopic dermatitis research.

The most relevant international meeting on atopic dermatitis, The George Rajka International Symposium on Atopic Dermatitis, took place in May 2008 in Kyoto (Japan). In 1979 in Oslo, Prof. Georg Rajka initiated a series of international meetings on atopic dermatitis (AD) called ISAD (International Symposium on Atopic Dermatitis) to take place approximately every third year. This meeting brings together clinicians and scientists interested in atopic dermatitis in an interdisciplinary atmosphere, and provides state-of-the-art on clinical and experimental research on this disease. Atopic dermatitis is a chronic cutaneous disease that very often is associated with other atopic disorders like asthma and allergic rhinitis. The meeting reflected on the latest novelties in the field related to abnormal skin barrier function, decreased innate immune response, influence of allergic inflammation on skin barrier/innate response, microbial infections as well future therapies for AD.

Recent advances in research and treatment of neurological disorders.

This year the American Academy of Neurology celebrated its 60th Annual Meeting that brought together over 10,000 neurologists and neuroscientists from all over the world in Chicago, Illinois. This report highlights relevant presentations covering the pathophysiology of neurological disorders, investigational therapies and biomarkers that will allow better diagnosis, monitoring and treatment of patients with neurological disease.

Unraveling the mechanisms of rare diseases.

The European Science Foundation (ESF) in collaboration with the University of Barcelona (UB) brought together leading scientists worldwide for an event that gave new insights into the structural biology, physiology and genetics of ion channels and transporters involved in rare inherited diseases. The meeting took place in San Feliu de Guixols, one of the most amazing venues on the Catalan coast.

Latest discoveries in allergy and clinical immunology.

Among all the international societies of allergy (AAAAI, EAACI, WAO, etc.), the Collegium Internationale Allergologicum (CIA) remains a selected and reduced group of about 200 of the most relevant investigators in the field of allergy and clinical immunology who come together to discuss current issues in allergy. The society holds a symposium every 2 years. This year, the 27th Symposium of the Collegium Internationale Allergologicum took place in Curaçao. This report contains a selection of some of the more currently relevant work presented, namely on basophils and mast cells, infection and asthma exacerbation, genes, pathophysiology and novel therapeutic approaches. Specific information about CIA can be found at http://www.ciaweb.org.

Spotlight on autoimmune lymphoproliferative syndrome.

This month's Spotlight on... reviews autoimmune lymphoproliferative syndrome (ALPS) and its treatment. ALPS is an inherited disease caused by defects in lymphocyte apoptosis that cause nonmalignant proliferation of lymphocytes with autoimmune manifestations. Although there is yet no specific treatment for ALPS, therapies selectively targeting lymphocyte apoptosis may open a new avenue in the treatment of this rare disorder.

The role of statins in erectile dysfunction.

Erectile dysfunction is a common disorder that involves impairment of the vascular endothelium and has been associated with cardiovascular disease. Despite the general effectiveness of phosphodiesterase type 5 (PDE5) inhibitors, some erectile dysfunction patients are resistant to or do not tolerate treatment with them, thus requiring further treatment alternatives. Statins have emerged as a promising therapeutic option due to their multiple modes of action. The use of statins as adjuvant or alternative therapy in erectile dysfunction has opened new avenues for the treatment of this disorder.

Emerging therapeutic strategies for chronic inflammatory diseases.

The 6th edition of the "Days of Molecular Medicine" conference was held at the Karolinska Institute in Stockholm, Sweden, May 24-27, 2006, and focused on the role of inflammation in chronic disease. The meeting, organized by The Nature Publishing Group, the Massachusetts General Hospital and the Karolinska Institute, brought together an international panel of speakers who discussed recent advances in the molecular pathology of chronic inflammatory diseases. This congress report summarizes the most relevant presentations highlighting novel targets for therapeutic intervention.

Spotlight on targeting aminoacyl-tRNA synthetases for the treatment of fungal infections.

This month's Spotlight on... focuses on targeting aminoacyl-tRNA synthetases for the treatment of fungal infections. The emergence of drug-resistant strains of bacterial and fungal pathogens has led to the development of new antibiotic strategies. Aminoacyl-tRNA synthetases, crucial for protein synthesis, represent a new target for the treatment of different infectious diseases.