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BACKGROUND: Medical school students in high-stress environments have been shown to make poor personal health decisions ranging from less healthy selections of food to lower rates of exercise. With the emergence of the COVID-19 pandemic adding a major social and health challenge, it is important to examine the effect this new stressor has on the health habits of medical school students. METHODS: All first-year students at Albany Medical College completed a self-recorded three-day log of food intake and exercise modality and duration. Reported data included calories, carbohydrates, protein, lipids, sodium, calcium, and other micronutrients. The data was divided between pre-pandemic (2018-19) and mid-pandemic (2020-21) entries. T-tests and ANOVA tests were used to compare for significance. RESULTS: Students consumed significantly fewer calories during the pandemic compared to before. This reduction was primarily driven by the female cohort of students. Specifically, this reduction in calories appears to be driven by a decrease in carbohydrate consumption, rather than lipids or protein, which did not change. Additionally, there were significant decreases in sodium, calcium, and vitamin D intake. The mid-pandemic time span (2020-21) appears to be correlated with decreased caloric intake, as well as other important nutrients such as vitamin D and calcium. CONCLUSIONS: This study demonstrated a decrease in calories, carbohydrates, sodium, and alcohol consumption when comparing pre- and mid-pandemic dietary habits of first-year medical students. It also indicated less than the recommended amount of calcium and Vitamin D consumption. Such changes may indicate restrictive eating habits in times of stress.
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Among the thousands of eHealth tools available, the vast majority do not get past pilot phases because they cannot prove value, and only a few have been systematically assessed. Although multiple eHealth assessment frameworks have been developed, these efforts face multiple challenges. This study aimed to address some of these challenges by validating and refining an initial list of 55 assessment criteria based on previous frameworks through a two-round modified Delphi process with in-between rounds of interviews. The expert panel (n = 57) included participants from 18 countries and 9 concerned parties. A consensus was reached on 46 criteria that were classified into foundational and contextual criteria. The 36 foundational criteria focus on evaluating the eHealth tool itself and were grouped into nine clusters: technical aspects, clinical utility and safety, usability and human centricity, functionality, content, data management, endorsement, maintenance, and developer. The 10 contextual criteria focus on evaluating the factors that vary depending on the context the tool is being evaluated for and were grouped into seven clusters: data-protection compliance, safety regulatory compliance, interoperability and data integration, cultural requirements, affordability, cost-benefit, and implementability. The classification of criteria into foundational and contextual helps us assess not only the quality of an isolated tool, but also its potential fit in a specific setting. Criteria subscales may be particularly relevant when determining the strengths and weaknesses of the tool being evaluated. This granularity enables different concerned parties to make informed decisions about which tools to consider according to their specific needs and priorities.
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BACKGROUND: Technological advancements have opened the path for many technology providers to easily develop and introduce eHealth tools to the public. The use of these tools is increasingly recognized as a critical quality driver in health care; however, choosing a quality tool from the myriad of tools available for a specific health need does not come without challenges. OBJECTIVE: This review aimed to systematically investigate the literature to understand the different approaches and criteria used to assess the quality and impact of eHealth tools by considering sociotechnical factors (from technical, social, and organizational perspectives). METHODS: A structured search was completed following the participants, intervention, comparators, and outcomes framework. We searched the PubMed, Cochrane, Web of Science, Scopus, and ProQuest databases for studies published between January 2012 and January 2022 in English, which yielded 675 results, of which 40 (5.9%) studies met the inclusion criteria. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions were followed to ensure a systematic process. Extracted data were analyzed using NVivo (QSR International), with a thematic analysis and narrative synthesis of emergent themes. RESULTS: Similar measures from the different papers, frameworks, and initiatives were aggregated into 36 unique criteria grouped into 13 clusters. Using the sociotechnical approach, we classified the relevant criteria into technical, social, and organizational assessment criteria. Technical assessment criteria were grouped into 5 clusters: technical aspects, functionality, content, data management, and design. Social assessment criteria were grouped into 4 clusters: human centricity, health outcomes, visible popularity metrics, and social aspects. Organizational assessment criteria were grouped into 4 clusters: sustainability and scalability, health care organization, health care context, and developer. CONCLUSIONS: This review builds on the growing body of research that investigates the criteria used to assess the quality and impact of eHealth tools and highlights the complexity and challenges facing these initiatives. It demonstrates that there is no single framework that is used uniformly to assess the quality and impact of eHealth tools. It also highlights the need for a more comprehensive approach that balances the social, organizational, and technical assessment criteria in a way that reflects the complexity and interdependence of the health care ecosystem and is aligned with the factors affecting users' adoption to ensure uptake and adherence in the long term.
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BACKGROUND: Research has shown that patient engagement is most commonly done at the beginning of research or to test readily available prototypes and less commonly done in other phases such as the execution phases. Previous studies have reported that patients are usually assigned a consultative rather than a decision-making role in health service planning and evaluation. OBJECTIVE: This study had 2 objectives: to better understand the challenges and opportunities in the inclusion of patients in the development of eHealth technologies and ideas on how to overcome the identified gaps and to create a research-based end-to-end practical blueprint that can guide the relevant stakeholders to successfully engage patients as cocreators in all human-centered design phases rather than mere testers of preplanned prototypes. METHODS: Key informant interviews were conducted using in-depth semistructured interviews with 20 participants from 6 countries across Europe. This was followed by a focus group to validate the initial findings. Participants encompassed all the relevant stakeholder groups including patient experts, eHealth experts, health technology providers, clinicians, pharma executives, and health insurance experts. RESULTS: This study shows that engaging patients in eHealth development can help provide different types of value; namely, identifying unmet needs, better usability and desirability, better fit into the patient journey, better adoption and stickiness, better health outcomes, advocacy and trust, a sense of purpose, and better health equity and access. However, the participants agreed that patients are usually engaged too late in the development process, mostly assuming a sounding role in testing a ready-made prototype. The justification for these gaps in engagement is driven by some prominent barriers, notably compliance risks, patient-related factors, power dynamics, patient engagement as lip service, poor value perception, lack of resources, mistrust, and inflexibility. On the positive side, the participants also reflected on facilitators for better patient engagement; for instance, engaging through engagement partners, novel approaches such as the rise of professional patient experts, embedding patients in development teams, expectation management, and professional moderation services. CONCLUSIONS: Overcoming the current gaps in patient engagement in eHealth development requires consolidated efforts from all stakeholders in a complex health care ecosystem. The shift toward more patient-driven eHealth development requires education and awareness; frameworks to monitor and evaluate the value of patient engagement; regulatory clarity and simplification; platforms to facilitate patient access and identification; patient incentivization, transparency, and trust; and a mindset shift toward value-based health care.
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[This corrects the article DOI: 10.2196/15935.].
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BACKGROUND: Mobile health (mHealth) tools have emerged as a promising health care technology that may contribute to cost savings, better access to care, and enhanced clinical outcomes; however, it is important to ensure their acceptance and adoption to harness this potential. Patient adoption has been recognized as a key challenge that requires further exploration. OBJECTIVE: The aim of this review was to systematically investigate the literature to understand the factors affecting patients' adoption of mHealth tools by considering sociotechnical factors (from technical, social, and health perspectives). METHODS: A structured search was completed following the participants, intervention, comparators, and outcomes framework. We searched the MEDLINE, PubMed, Cochrane Library, and SAGE databases for studies published between January 2011 and July 2021 in the English language, yielding 5873 results, of which 147 studies met the inclusion criteria. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook were followed to ensure a systematic process. Extracted data were analyzed using NVivo (QSR International), with thematic analysis and narrative synthesis of emergent themes. RESULTS: The technical factors affecting patients' adoption of mHealth tools were categorized into six key themes, which in turn were divided into 20 subthemes: usefulness, ease of use, data-related, monetary factors, technical issues, and user experience. Health-related factors were categorized into six key themes: the disease or health condition, the care team's role, health consciousness and literacy, health behavior, relation to other therapies, integration into patient journey, and the patients' insurance status. Social and personal factors were divided into three key clusters: demographic factors, personal characteristics, and social and cultural aspects; these were divided into 19 subthemes, highlighting the importance of considering these factors when addressing potential barriers to mHealth adoption and how to overcome them. CONCLUSIONS: This review builds on the growing body of research that investigates patients' adoption of mHealth services and highlights the complexity of the factors affecting adoption, including personal, social, technical, organizational, and health care aspects. We recommend a more patient-centered approach by ensuring the tools' fit into the overall patient journey and treatment plan, emphasizing inclusive design, and warranting comprehensive patient education and support. Moreover, empowering and mobilizing clinicians and care teams, addressing ethical data management issues, and focusing on health care policies may facilitate adoption.
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Telemedicine , Biomedical Technology , Delivery of Health Care , Humans , Organizations , Publications , Telemedicine/methodsABSTRACT
BACKGROUND: Cancer immunotherapy (CIT), as a monotherapy or in combination with chemotherapy, has been shown to extend overall survival in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). However, patients experience treatment-related symptoms that they are required to recall between hospital visits. Digital patient monitoring and management (DPMM) tools may improve clinical practice by allowing real-time symptom reporting. OBJECTIVE: This proof-of-concept pilot study assessed patient and health care professional (HCP) adoption of our DPMM tool, which was designed specifically for patients with advanced or metastatic NSCLC treated with CIT, and the tool's impact on clinical care. METHODS: Four advisory boards were assembled in order to co-develop a drug- and indication-specific CIT (CIT+) module, based on a generic CIT DPMM tool from Kaiku Health, Helsinki, Finland. A total of 45 patients treated with second-line single-agent CIT (ie, atezolizumab or otherwise) for advanced or metastatic NSCLC, as well as HCPs, whose exact number was decided by the clinics, were recruited from 10 clinics in Germany, Finland, and Switzerland between February and May 2019. All clinics were provided with the Kaiku Health generic CIT DPMM tool, including our CIT+ module. Data on user experience, overall satisfaction, and impact of the tool on clinical practice were collected using anonymized surveys-answers ranged from 1 (low agreement) to 5 (high agreement)-and HCP interviews; surveys and interviews consisted of closed-ended Likert scales and open-ended questions, respectively. The first survey was conducted after 2 months of DPMM use, and a second survey and HCP interviews were conducted at study end (ie, after ≥3 months of DPMM use); only a subgroup of HCPs from each clinic responded to the surveys and interviews. Survey data were analyzed quantitatively; interviews were recorded, transcribed verbatim, and translated into English, where applicable, for coding and qualitative thematic analysis. RESULTS: Among interim survey respondents (N=51: 13 [25%] nurses, 11 [22%] physicians, and 27 [53%] patients), mean rankings of the tool's seven usability attributes ranged from 3.2 to 4.4 (nurses), 3.7 to 4.5 (physicians), and 3.7 to 4.2 (patients). At the end-of-study survey (N=48: 19 [40%] nurses, 8 [17%] physicians, and 21 [44%] patients), most respondents agreed that the tool facilitated more efficient and focused discussions between patients and HCPs (nurses and patients: mean rating 4.2, SD 0.8; physicians: mean rating 4.4, SD 0.8) and allowed HCPs to tailor discussions with patients (mean rating 4.35, SD 0.65). The standalone tool was well integrated into HCP daily clinical workflow (mean rating 3.80, SD 0.75), enabled workflow optimization between physicians and nurses (mean rating 3.75, SD 0.80), and saved time by decreasing phone consultations (mean rating 3.75, SD 1.00) and patient visits (mean rating 3.45, SD 1.20). Workload was the most common challenge of tool use among respondents (12/19, 63%). CONCLUSIONS: Our results demonstrate high user satisfaction and acceptance of DPMM tools by HCPs and patients, and highlight the improvements to clinical care in patients with advanced or metastatic NSCLC treated with CIT monotherapy. However, further integration of the tool into the clinical information technology data flow is required. Future studies or registries using our DPMM tool may provide insights into significant effects on patient quality of life or health-economic benefits.
Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Health Personnel/standards , Immunotherapy/methods , Lung Neoplasms/therapy , Quality of Life/psychology , Carcinoma, Non-Small-Cell Lung/immunology , Female , Humans , Lung Neoplasms/immunology , Male , Pilot Projects , Proof of Concept Study , Surveys and QuestionnairesABSTRACT
BACKGROUND: Mobile health (mHealth) tools have shown promise in clinical photo and wound documentation for their potential to improve workflows, expand access to care, and improve the quality of patient care. However, some barriers to adoption persist. OBJECTIVE: This study aims to understand the social, organizational, and technical factors affecting clinicians' adoption of a clinical photo documentation mHealth app and its implications for clinical workflows and quality of care. METHODS: A qualitative case study of a clinical photo and wound documentation app called imitoCam was conducted. The data were collected through 20 in-depth interviews with mHealth providers, clinicians, and medical informatics experts from 8 clinics and hospitals in Switzerland and Germany. RESULTS: According to the study participants, the use of mHealth in clinical photo and wound documentation provides numerous benefits such as time-saving and efficacy, better patient safety and quality of care, enhanced data security and validation, and better accessibility. The clinical workflow may also improve when the app is a good fit, resulting in better collaboration and transparency, streamlined daily work, clinician empowerment, and improved quality of care. The findings included important factors that may contribute to or hinder adoption. Factors may be related to the material nature of the tool, such as the perceived usefulness, ease of use, interoperability, cost, or security of the app, or social aspects such as personal experience, attitudes, awareness, or culture. Organizational and policy barriers include the available clinical practice infrastructure, workload and resources, the complexity of decision making, training, and ambiguity or lack of regulations. User engagement in the development and implementation process is a vital contributor to the successful adoption of mHealth apps. CONCLUSIONS: The promising potential of mHealth in clinical photo and wound documentation is clear and may enhance clinical workflow and quality of care; however, the factors affecting adoption go beyond the technical features of the tool itself to embrace significant social and organizational elements. Technology providers, clinicians, and decision makers should work together to carefully address any barriers to improve adoption and harness the potential of these tools.
Subject(s)
Mobile Applications , Documentation , Female , Germany , Humans , Male , Quality of Health Care , Switzerland , WorkflowABSTRACT
In this work, we present a trimetal neodymium complex with two notable qualities. First, the assembly of the complex is templated by peroxide derived from atmospheric oxygen. Second, the bulk material behaves as a superparamagnet, implying that the individual complexes are molecular magnets. Peroxide-templated assembly is possible because of the confluence of the high oxophilicity of neodymium along with the use of an azeotropic distillation synthesis method, which excludes water but admits oxygen. SQUID magnetometry measurements show an extremely high magnetic susceptibility as well as a lack of remanence.
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BACKGROUND: Although there is a push toward encouraging mobile health (mHealth) adoption to harness its potential, there are many challenges that sometimes go beyond the technology to involve other elements such as social, cultural, and organizational factors. OBJECTIVE: This review aimed to explore which frameworks are used the most, to understand clinicians' adoption of mHealth as well as to identify potential shortcomings in these frameworks. Highlighting these gaps and the main factors that were not specifically covered in the most frequently used frameworks will assist future researchers to include all relevant key factors. METHODS: This review was an in-depth subanalysis of a larger systematic review that included research papers published between 2008 and 2018 and focused on the social, organizational, and technical factors impacting clinicians' adoption of mHealth. The initial systematic review included 171 studies, of which 50 studies used a theoretical framework. These 50 studies are the subject of this qualitative review, reflecting further on the frameworks used and how these can help future researchers design studies that investigate the topic of mHealth adoption more robustly. RESULTS: The most commonly used frameworks were different forms of extensions of the Technology Acceptance Model (TAM; 17/50, 34%), the diffusion of innovation theory (DOI; 8/50, 16%), and different forms of extensions of the unified theory of acceptance and use of technology (6/50, 12%). Some studies used a combination of the TAM and DOI frameworks (3/50, 6%), whereas others used the consolidated framework for implementation research (3/50, 6%) and sociotechnical systems (STS) theory (2/50, 4%). The factors cited by more than 20% of the studies were usefulness, output quality, ease of use, technical support, data privacy, self-efficacy, attitude, organizational inner setting, training, leadership engagement, workload, and workflow fit. Most factors could be linked to one framework or another, but there was no single framework that could adequately cover all relevant and specific factors without some expansion. CONCLUSIONS: Health care technologies are generally more complex than tools that address individual user needs as they usually support patients with comorbidities who are typically treated by multidisciplinary teams who might even work in different health care organizations. This special nature of how the health care sector operates and its highly regulated nature, the usual budget deficits, and the interdependence between health care organizations necessitate some crucial expansions to existing theoretical frameworks usually used when studying adoption. We propose a shift toward theoretical frameworks that take into account implementation challenges that factor in the complexity of the sociotechnical structure of health care organizations and the interplay between the technical, social, and organizational aspects. Our consolidated framework offers recommendations on which factors to include when investigating clinicians' adoption of mHealth, taking into account all three aspects.
Subject(s)
Practice Patterns, Physicians' , Telemedicine , Biomedical Technology , Humans , WorkflowABSTRACT
BACKGROUND: There is a growing body of evidence highlighting the potential of mobile health (mHealth) in reducing health care costs, enhancing access, and improving the quality of patient care. However, user acceptance and adoption are key prerequisites to harness this potential; hence, a deeper understanding of the factors impacting this adoption is crucial for its success. OBJECTIVE: The aim of this review was to systematically explore relevant published literature to synthesize the current understanding of the factors impacting clinicians' adoption of mHealth tools, not only from a technological perspective but also from social and organizational perspectives. METHODS: A structured search was carried out of MEDLINE, PubMed, the Cochrane Library, and the SAGE database for studies published between January 2008 and July 2018 in the English language, yielding 4993 results, of which 171 met the inclusion criteria. The Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and the Cochrane handbook were followed to ensure a systematic process. RESULTS: The technological factors impacting clinicians' adoption of mHealth tools were categorized into eight key themes: usefulness, ease of use, design, compatibility, technical issues, content, personalization, and convenience, which were in turn divided into 14 subthemes altogether. Social and organizational factors were much more prevalent and were categorized into eight key themes: workflow related, patient related, policy and regulations, culture or attitude or social influence, monetary factors, evidence base, awareness, and user engagement. These were divided into 41 subthemes, highlighting the importance of considering these factors when addressing potential barriers to mHealth adoption and how to overcome them. CONCLUSIONS: The study results can help inform mHealth providers and policymakers regarding the key factors impacting mHealth adoption, guiding them into making educated decisions to foster this adoption and harness the potential benefits.
Subject(s)
Mobile Applications , Telemedicine , Humans , Organizations , PublicationsABSTRACT
Automated handling of microscale objects is essential for manufacturing of next-generation electronic systems. Yet, mechanical pick-and-place technologies cannot manipulate smaller objects whose surface forces dominate over gravity, and emerging microtransfer printing methods require multidirectional motion, heating, and/or chemical bonding to switch adhesion. We introduce soft nanocomposite electroadhesives (SNEs), comprising sparse forests of dielectric-coated carbon nanotubes (CNTs), which have electrostatically switchable dry adhesion. SNEs exhibit 40-fold lower nominal dry adhesion than typical solids, yet their adhesion is increased >100-fold by applying 30 V to the CNTs. We characterize the scaling of adhesion with surface morphology, dielectric thickness, and applied voltage and demonstrate digital transfer printing of films of Ag nanowires, polymer and metal microparticles, and unpackaged light-emitting diodes.
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BACKGROUND: Despite the existence of adequate technological infrastructure and clearer policies, there are situations where users, mainly physicians, resist mobile health (mHealth) solutions. This is of particular concern, bearing in mind that several studies, both in developed and developing countries, showed that clinicians' adoption is the most influential factor in such solutions' success. OBJECTIVE: The aim of this study was to focus on understanding clinicians' roles in the adoption of an oncology decision support app, the factors impacting this adoption, and its implications for organizational and social practices. METHODS: A qualitative case study of a decision support app in oncology, called ONCOassist, was conducted. The data were collected through 17 in-depth interviews with clinicians and nurses in the United Kingdom, Ireland, France, Italy, Spain, and Portugal. RESULTS: This case demonstrates the affordances and constraints of mHealth technology at the workplace, its implications for the organization of work, and clinicians' role in its constant development and adoption. The research findings confirmed that factors such as app operation and stability, ease of use, usefulness, cost, and portability play a major role in the adoption decision; however, other social factors such as endorsement, neutrality of the content, attitude toward technology, existing workload, and internal organizational politics are also reported as key determinants of clinicians' adoption. Interoperability and cultural views of mobile usage at work are the key workflow disadvantages, whereas higher efficiency and performance, sharpened practice, and location flexibility are the main workflow advantages. CONCLUSIONS: Several organizational implications emerged, suggesting the need for some actions such as fostering a work culture that embraces new technologies and the creation of new digital roles for clinicians both on the hospitals or clinics and on the development sides but also more collaboration between health care organizations and digital health providers to enable electronic medical record integration and solving of any interoperability issues. From a theoretical perspective, we also suggest the addition of a fourth step to Leonardi's methodological guidance that accounts for user engagement; embedding the users in the continuous design and development processes ensures the understanding of user-specific affordances that can then be made more obvious to other users and increase the potential of such tools to go beyond their technological features and have a higher impact on workflow and the organizing process.
Subject(s)
Health Personnel/psychology , Medical Oncology/instrumentation , Mobile Applications/standards , Adult , Attitude of Health Personnel , Case-Control Studies , Decision Support Techniques , Europe , Female , Health Personnel/statistics & numerical data , Humans , Interviews as Topic/methods , Male , Medical Oncology/methods , Middle Aged , Mobile Applications/statistics & numerical data , Professional Role/psychology , Qualitative ResearchABSTRACT
Understanding of the liquid imbibition dynamics in nanoporous materials is important to advances in chemical separations, phase change heat transfer, electrochemical energy storage, and diagnostic assays. We study the liquid imbibition behavior in films of ceramic-coated vertically aligned carbon nanotubes (CNTs). The nanoscale porosity of the films is tuned by conformal ceramic coating via atomic layer deposition (ALD), enabling stable liquid imbibition and precise measurement of the imbibition dynamics without capillary densification of the CNTs. We show that the imbibition rate decreases as the ceramic coating thickness increases, which effectively changes the CNT-CNT spacing and therefore decreases the permeability. We derive a model, based on Darcy's law, that incorporates an expression for the permeability of nanoscale post arrays, and we show that the model fits the experimental results with high accuracy. The tailorable porosity, along with controllable surface wettability and mechanical stability of coated CNTs, suggest their suitability for application-guided engineering, and for further investigation of imbibition behavior at finer length scales.
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The leading cause of morbidity and mortality in infants is hypoxia-ischemia (HI). The current therapies for HI have limited success, in part due to a lack of understanding of HI pathophysiology and underlying mechanisms. Herein, a neonatal rat model of HI was used to examine the changes in brain swelling and infarct volume over 4 days after HI. Forty-four P10 rat pups were sacrificed at 2, 3, or 4 days post-HI. After sacrifice, the brains were removed, sliced, and stained with TTC (2,3,5-triphenyl-2H-tetrazolium chloride). Images of TTC-stained brains were used for measurement of the ipsilateral hemisphere brain volumes and infarct volumes, calculated using standard equations. The hemispheric brain volumes of HI animals in all groups was lower than that of sham animals and decreased as the post-HI sacrifice time increased. The infarct volume of HI animals was larger than that of sham animals. Infarct volumes tended to decrease over the days post-HI. The change in infarct volume is likely the result of a combination of brain growth and repair mechanisms. However, changes in the hemispheric brain volume may include tissue growth and repair mechanism, so also may be a limitation of the current algorithm used for calculating ipsilateral hemisphere brain volume.
Subject(s)
Brain Edema/pathology , Brain Infarction/pathology , Brain/pathology , Hypoxia-Ischemia, Brain/pathology , Animals , Animals, Newborn , Disease Models, Animal , Disease Progression , Organ Size , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is an inhibitor of caspases 3 and 9 that is overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report an open-label randomized phase II trial of reinduction chemotherapy with and without the XIAP antisense oligonucleotide AEG35156 in patients with AML who did not achieve remission with initial induction chemotherapy. METHODS: Twenty-seven patients with AML who were refractory to initial induction chemotherapy were randomized and treated with AEG35156 (650 mg) in combination with high-dose cytarabine and idarubicin. Thirteen patients were randomized and treated with high-dose cytarabine and idarubicin alone. The rates of response and toxicity were determined. RESULTS: Of the 27 patients assigned to AEG35156 in combination with high-dose cytarabine and idarubicin, 3 died during reinduction chemotherapy, 5 achieved complete remission (CR), and 6 achieved CR with incomplete platelet count recovery (CRp), for an overall response rate of 41%. Of the 13 patients assigned to the control arm of the study, none died during reinduction, 6 achieved CR, and 3 achieved CRp, for an overall response rate of 69%. The differences in response rates between patients in the AEG35156 and control arms were not statistically different (P = 0.18 by the χ(2) test). CONCLUSIONS: The addition of AEG35156 to reinduction chemotherapy was well tolerated but did not improve rates of remission. Therefore alternative therapeutic strategies should be explored in patients with AML refractory to induction chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Oligonucleotides/administration & dosage , X-Linked Inhibitor of Apoptosis Protein/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Remission Induction , Treatment Outcome , X-Linked Inhibitor of Apoptosis Protein/genetics , Young AdultABSTRACT
Epidemiological studies suggest that consumption of tomato products reduces the risk of CVD via antioxidant, hypocholesterolaemic and anti-inflammatory mechanisms. Although experimental data also describe beneficial effects on endothelial function, clinical data in human subjects are lacking. To test the hypothesis that tomato ingestion ameliorates endothelial function, we randomised healthy non-smoking postmenopausal women to consume a buttered roll with and without tomato purée (70 g) in a cross-over design. Endothelial-dependent flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation of the brachial artery were assessed with high-resolution ultrasound (13 MHz linear array transducer). Acute (24 h) and long-term (7 d) effects were examined after daily consumption of the described meal. Nineteen volunteers completed the protocol and provided technically suitable ultrasound measurement data. Plasma lycopene levels increased from 0·30 (sem 0·04) (baseline) to 0·42 (sem 0·04) and to 0·74 (sem 0·06) µm after 24 h and 7 d, respectively, with tomato purée consumption. These data indicated an effective absorption of the tomato product. However, both acute and long-term tomato purée consumption had no effects on endothelium-dependent or -independent dilation of the brachial artery. In addition, we found no correlation between lycopene plasma levels and FMD. In conclusion, consumption of tomato products associated with a significant increase in plasma lycopene levels had no effects on endothelial function in healthy postmenopausal women.
Subject(s)
Cardiovascular Diseases/prevention & control , Diet , Endothelium, Vascular/physiology , Solanum lycopersicum , Aged , Brachial Artery/diagnostic imaging , Brachial Artery/physiology , Cardiovascular Diseases/physiopathology , Carotenoids/blood , Cross-Over Studies , Endothelium, Vascular/diagnostic imaging , Female , Humans , Lycopene , Menopause , Middle Aged , Ultrasonography , Vasodilation/physiologyABSTRACT
Branching processes are stochastic individual-based processes leading consequently to a bottom-up approach. In addition, since the state variables are random integer variables (representing population sizes), the extinction occurs at random finite time on the extinction set, thus leading to fine and realistic predictions. Starting from the simplest and well-known single-type Bienaymé-Galton-Watson branching process that was used by several authors for approximating the beginning of an epidemic, we then present a general branching model with age and population dependent individual transitions. However contrary to the classical Bienaymé-Galton-Watson or asymptotically Bienaymé-Galton-Watson setting, where the asymptotic behavior of the process, as time tends to infinity, is well understood, the asymptotic behavior of this general process is a new question. Here we give some solutions for dealing with this problem depending on whether the initial population size is large or small, and whether the disease is rare or non-rare when the initial population size is large.
Subject(s)
Epidemiologic Studies , Humans , Stochastic ProcessesABSTRACT
PURPOSE: X-linked inhibitor of apoptosis protein (XIAP) is an inhibitor of caspases 3 and 9 which are overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report on a phase I/II trial of the XIAP antisense oligonucleotide AEG35156 in combination with reinduction chemotherapy. PATIENTS AND METHODS: Twenty-four patients with rapidly relapsed or refractory AML were treated with escalating doses of AEG35156 (12 to 250 mg/m(2)) as an intravenous solution over 2 hours and 32 patients were treated with the highest planned dose of 350 mg/m(2) in combination with idarubicin and high-dose cytarabine reinduction chemotherapy. Correlative studies were conducted to determine the effects of AEG35156 on levels of XIAP mRNA. RESULTS: Knockdown of XIAP mRNA during treatment increased with the dose of the antisense. All patients who received 350 mg/m(2) of AEG35156 had higher than 30% target knockdown with a median maximal knockdown of 90% (range, 48% to 100%). The overall response rate was higher among the patients receiving the highest dose of AEG35156. In this group, 15 (47%) of 32 patients achieved complete response (CR)/CR with incomplete platelet count recovery (CRp) compared with only one (4%) of 24 receiving 12 to 250 mg/m(2) AEG35156. Among the patients receiving 350 mg/m(2) of AEG35156 in combination with chemotherapy, 10 (91%) of 11 who were refractory to a single induction chemotherapy regimen achieved CR/CRp after reinduction with AEG35156 and chemotherapy. AEG35156 was well tolerated save for two cases of peripheral neuropathy in patients receiving multiple doses of AEG35156. CONCLUSION: At the highest dose tested, AEG35156 knocks down its target and appears very effective when combined with chemotherapy in patients with AML refractory to a single induction regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid/drug therapy , Acute Disease , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Idarubicin/administration & dosage , Idarubicin/adverse effects , Leukemia, Myeloid/pathology , Male , Middle Aged , Oligonucleotides/administration & dosage , Peripheral Nervous System Diseases/chemically induced , RNA, Messenger/genetics , RNA, Messenger/metabolism , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome , X-Linked Inhibitor of Apoptosis Protein/geneticsABSTRACT
The aim of this article is to build a methodology allowing the study and the comparison of the potential spread of BSE at the scale of countries under different routine slaughtering conditions in order to evaluate the risk of nonextinction due to this slaughtering. We first model the evolution in discrete time of the proportion of animals in the latent period and that of infectives, assuming a very large branching population not necessarily constant in size, two age classes, less than 1-year-old animals, and adult animals. We analytically derive a bifurcation parameter rho(0) allowing us to predict either endemicity or extinction of the disease, which has the meaning of an epidemiological reproductive rate. We show that the classical reproductive number R(0) cannot be used for prediction if the size of the population, when healthy, does not remain stable throughout time. We illustrate the qualitative results by means of simulations with either the British routine slaughtering probabilities or the French ones, the other conditions being assumed identical in both countries. We show that the French probabilities lead to a higher risk of spread of the disease than the British ones, this result being mainly due to a smaller value of the routine slaughtering probability of the adult animals in France than in Great Britain.