Global Diversification in Medicine Regulation: Insights from Regenerative Stem Cell Medicine

This is the final version. Available on open access from Taylor & Francis via the DOI in this record. Data Access Statement: The research data supporting this publication are provided within this paper.Medicine regulation worldwide has undergone a process of regulatory diversification. The evidence-based medicine (EBM) paradigm, centered on multi-phase randomized controlled trials, is increasingly contested and replaced by new models of clinical validation. To explain these changes, STS research has cited just a few factors, e.g. growing pressure form health consumers; the role of pharmaceutical companies to lobby for fast, affordable drug development; the influence of neoliberal ideas and libertarian advocacy of deregulation; and the agency of national governments to enable domestic innovation opportunities in the context of global competition and inequalities. Those factors individually cannot account for the increasing variation in medicine regulation at both national and global levels. Instead it is helpful to integrate elements of existing explanations into a framework with four pairs of conflicting regulatory choices, which play a central role in the formation of medicine regulation. We use this framework to compare regulatory changes in the USA, European Union, China, India, Argentina, and Japan. Across these jurisdictions, the case studies illustrate four dynamics of diversification. Key regulatory concepts such as evidence, risk, safety, efficacy, responsibility and accountability acquire different meanings, reshaping medicine innovation in far-reaching and often contradictory ways. The boundaries between medical research and healthcare provision, commerce and humanitarian service, as well as state control and medical self-regulation are re-defined.Economic and Social Research Council (ESRC)European Research CouncilUniversidad Nacional de Quilme

Swimming in ice cold water

Introduction: We investigated two athletes swimming in 4°C for 23min (1.3km, swimmer 1) and 42min (2.2km, swimmer 2), respectively. Materials and methods: Pre swim, percent body fat was determined; post swim, core temperature was measured. Results: The core temperature of swimmer 2 was: 37.0°C immediately before the start, 32°C 20min after getting out of the water, and 35.5°C 80min after finishing the swim. Conclusion: We assume that the higher skin-fold thickness and body fat of swimmer 2 enabled him to perform longer. In addition to this, mental power and experience in cold water swimming must be considered. In any athlete aiming at swimming in water of less than 5°C, body core temperature and heart rate should be continuously monitored in order to detect a body core temperature below 32°C and arrhythmia to pull the athlete out of the water before life-threatening circumstances occu

Beyond Control-Flow: Extending Business Process Configuration to Roles and Objects

A configurable process model is an integrated representation of multiple variants of a business process. It is designed to be individualized to meet a particular set of requirements. As such, configurable process models promote systematic reuse of proven or common practices. Existing notations for configurable process modeling focus on capturing tasks and control-flow dependencies, neglecting equally important aspects of business processes such as data flow, material flow and resource management. This paper fills this gap by proposing an integrated meta-model for configurable processes with advanced features for capturing resources involved in the performance of tasks (through task-role associations) as well as flow of data and physical artifacts (through task-object associations). Although embodied as an extension of a popular process modeling notation, namely EPC, the meta-model is defined in an abstract and formal manner to make it applicable to other notations

Dynamic Context Modeling for Agile Case Management

International audienceCase Management processes are characterized by their high unpredictability and, thus, cannot be handled following traditional process- or activity-centered approaches. Adaptive Case Management paradigm proposes an alternative data-centered approach for management such processes. In this paper, we elaborate on this approach and explore the role of context data in Case Management. We use the state-oriented representation of the process that allows us to incorporate the contextual information in a systematic and transparent way, leading towards agile case management

Health service utilization patterns of primary care patients with osteoarthritis

Contains fulltext : 53455.pdf ( ) (Open Access)BACKGROUND: To assess factors associated with visits to GPs, orthopaedists, and non-physician practitioners of complementary medicine (alternative practitioners) by primary care patients with osteoarthritis (OA). METHODS: Cross-sectional survey among 1250 consecutively addressed patients from 75 primary care practices in Germany. All patients suffered from OA of the knee or hip according to ACR criteria. They received questionnaires collecting sociodemographic data, data about health service utilisation, prescriptions, comorbidities. They also included established instruments as the Arthritis Impact Measurement Scale (AIMS2-SF) to assess disease-specific quality of life and the Patient Health Questionnaire (PHQ-9) to assess depression. Hierarchical stepwise multiple linear regression models were used to reveal significant factors influencing health service utilization. RESULTS: 1021 of 1250 (81.6%) questionnaires were returned. Nonrespondents did not differ from participants. Factors associated with health service use (HSU) varied between providers of care. Not being in a partnership, achieving a high score on the PHQ-9, increased pain severity reflected in the "symptom" scale of the AIMS2-SF, and an increased number of drug prescriptions predicted a high frequency of GP visits. The PHQ-9 score was also a predictor for visits to orthopaedists, as were previous GP contacts, a high score in the "symptom" scale as well as a high score in the "lower limb scale" of the AIMS2-SF. Regarding visits to alternative practitioners, a high score in the AIMS -"social" scale was a positive predictor as older people were less likely to visit them. CONCLUSION: Our results emphasize the need for awareness of psychological factors contributing to the use of health care providers. Addressing the revealed factors associated with HSU appropriately may lead to decreased health care utilization. But further research is needed to assess how this can be done successfully

A survey of attitudes toward clinical research among physicians at Kyoto University Hospital

<p>Abstract</p> <p>Background</p> <p>In Japan, only clinical research related to investigational new drug trials must be notified to regulatory bodies, and this lack of a uniform standard for clinical research has caused a number of difficulties. The objective of this study was to assess the willingness of physicians to participate in clinical research and to identify effective methods to promote and enhance clinical research.</p> <p>Methods</p> <p>We conducted a cross-sectional survey by administrating questionnaires to physicians in 31 departments in Kyoto University Hospital from October through November 2007.</p> <p>Results</p> <p>A total of 51.5% (310 of 602) of physicians completed the questionnaire. More than two-thirds of them reported currently participating in clinical research, and nearly all believed that clinical research is necessary for physicians. Less than 20% of respondents had specific training regarding clinical research, and most reported a need to acquire concepts and skills regarding clinical research, especially those related to statistics. "Paperwork was complicated and onerous" was the most frequently cited obstacle in conducting clinical research, followed by "few eligible patients" and "lack of time". Previous participation in and prospective participation in clinical research, previous writing a research protocol were positively associated with current participation in clinical research.</p> <p>Conclusions</p> <p>Physicians in university hospitals need more training regarding clinical research, particularly in biostatistics. They also require administrative assistance. Our findings indicate that the quality of clinical research could be improved if training in clinical research methodology and biostatistics were provided, and if greater assistance in the preparation of study documents requested by the institutional Independent Ethics Committee were available.</p

Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial.

The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature &gt;37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin &lt;8 g/dL and platelet count &lt;50 x 10 &lt;sup&gt;9&lt;/sup&gt; cells/L confirmed by recent laboratory test (&lt;90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance &lt;30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (&lt;90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. Patients will undergo block stratified randomization (by age: 50-70 vs. &gt;70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). In this open-label study, no blinding procedures will be used. The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-β = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol