Assessing the Potential Risks of Digital Therapeutics (DTX): The DTX Risk Assessment Canvas

Motivation: Digital therapeutics (DTX), i.e., health interventions that are provided through digital means, are increasingly available for use; in some countries, physicians can even prescribe selected DTX following a reimbursement by health insurances. This results in an increasing need for methodologies to consider and monitor DTX’s negative consequences, their risks to patient safety, and possible adverse events. However, it is completely unknown which aspects should be subject to surveillance given the missing experiences with the tools and their negative impacts. Objective: Our aim is to develop a tool—the DTX Risk Assessment Canvas—that enables researchers, developers, and practitioners to reflect on the negative consequences of DTX in a participatory process. Method: Taking the well-established business model canvas as a starting point, we identified relevant aspects to be considered in a risk assessment of a DTX. The aspects or building blocks of the canvas were constructed in a two-way process: first, we defined the aspects relevant for discussing and reflecting on how a DTX might bring negative consequences and risks for its users by considering ISO/TS 82304-2, the scientific literature, and by reviewing existing DTX and their listed adverse effects. The resulting aspects were grouped into thematic blocks and the canvas was created. Second, six experts in health informatics and mental health provided feedback and tested the understandability of the initial canvas by individually applying it to a DTX of their choice. Based on their feedback, the canvas was modified. Results: The DTX Risk Assessment Canvas is organized into 15 thematic blocks which are in turn grouped into three thematic groups considering the DTX itself, the users of the DTX, and the effects of the DTX. For each thematic block, questions have been formulated to guide the user of the canvas in reflecting on the single aspects. Conclusions: The DTX Risk Assessment Canvas is a tool to reflect the negative consequences and risks of a DTX by discussing different thematic blocks that together constitute a comprehensive interpretation of a DTX regarding possible risks. Applied during the DTX design and development phase, it can help in implementing countermeasures for mitigation or means for their monitoring

Statistics of extinction and survival in Lotka-Volterra systems

We analyze purely competitive many-species Lotka-Volterra systems with random interaction matrices, focusing the attention on statistical properties of their asymptotic states. Generic features of the evolution are outlined from a semiquantitative analysis of the phase-space structure, and extensive numerical simulations are performed to study the statistics of the extinctions. We find that the number of surviving species depends strongly on the statistical properties of the interaction matrix, and that the probability of survival is weakly correlated to specific initial conditions.Comment: Previous version had error in authors. 11 pages, including 5 figure

Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes

View full abstracthttps://openworks.mdanderson.org/leading-edge/1002/thumbnail.jp

Use and acceptance of long lasting insecticidal net screens for dengue prevention in Acapulco, Guerrero, Mexico

Background Dengue, recognized by the WHO as the most important mosquito-borne viral disease in the world, is a growing problem. Currently, the only effective way of preventing dengue is vector control. Standard methods have shown limited effect, and there have been calls to develop new integrated vector management approaches. One novel tool, protecting houses with long lasting insecticidal screens on doors and windows, is being trialled in a cluster randomised controlled trial by a joint UADY/WHO TDR/IDRC study in various districts of Acapulco, Mexico, with exceptionally high levels of crime and insecurity. This study investigated the community’s perspectives of long lasting insecticidal screens on doors and windows in homes and in schools, in order to ascertain their acceptability, to identify challenges to further implementation and opportunities for future improvements. Methods This was a sequential mixed-methods study. The quantitative arm contained a satisfaction survey administered to 288 houses that had received the intervention examining their perspectives of both the intervention and dengue prevention in general. The qualitative arm consisted of Focus Group Discussions (FGDs) with those who had accepted the intervention and key informant interviews with: schoolteachers to discuss the use of the screens in schools, program staff, and community members who had refused the intervention. Results Overall satisfaction and acceptance of the screens was very high, with only some operational and technical complaints relating to screen fragility and the installation process. However, the wider social context of urban violence and insecurity was a major barrier to screen acceptance. Lack of information dissemination and community collaboration were identified as project weaknesses. Conclusions The screens are widely accepted by the population, but the project implementation could be improved by reassuring the community of its legitimacy in the context of insecurity. More community engagement and better information sharing structures are needed. The screens could be a major new dengue prevention tool suitable for widespread use, if further research supports their entomological and epidemiological effectiveness and their acceptability in different social and environmental contexts. Further research is needed looking at the impact of insecurity of dengue prevention programmes

Short-term functional outcomes in patients undergoing primary total knee arthroplasty according to their body mass index

Background: The impact of an increased body mass index (BMI) in patients with ostheoarthritis who undergo total knee arthroplasty (TKA) remains a controversial variable in terms of risks and benefits. This study aimed to evaluate the influence of BMI in the functional outcomes of patients with ostheoarthritis who underwent TKA. Methods: We followed a cohort of patients who underwent total knee arthroplasty with a primary diagnosis of osteoarthritis. Patients were stratified into 3 groups according to the World Health Organization classification of BMI. We assessed the association between BMI group and functional scores using the Western Ontario and McMaster osteoarthritis index (WOMAC) over the time intervals of pre– and postoperatively at 1 month, 3 months and 1 year. Results: The difference in means between pre-surgical WOMAC and WOMAC at first follow-up according to each BMI group was divided as follows: normal 10.9 (p=0.195), overweight 15.7 (p≤0.001) and obese 20.6 (p≤0.001). Study participants with a higher BMI had worse preoperative WOMAC scores and had greater improvement from baseline to 1 month. After one year of follow-up, participants in all BMI groups had similar WOMAC scores. Conclusions: Patients with obesity who underwent TKA showed greater functional improvement one month after surgery compared to the other BMI groups. Subsequently, it was observed at the end of the 12-month follow-up that all patients, regardless of BMI, had improved functional outcomes, and the magnitude of improvement was similar in all BMI groups.

El Sistema Arrecifal Mesoamericano-México: consideraciones para su designación como Zona Marítima Especialmente Sensible

The Mesoamerican Barrier Reef System (MBRS) extends over 1,000 km along the Caribbean Sea of Mexico, Belize, Guatemala, and Honduras. From 1997 onwards these four countries have considered an initiative to designate the MBRS as a Particularly Sensitive Sea Area (PSSA) by the International Maritime Organization (IMO). The purpose of the initiative is to protect the MBRS against the negative effects of international shipping activities. Such designation would also constitute a mechanism to facilitate conservation and sustainable use of the regions resources. This paper provides a summary of the available information about ecological, socio-economic and shipping activities in the Mexican portion of the MBRS (State of Quintana Roo) that might contribute to the joint countries effort by identifying strengths and weaknesses in complying with the guidelines established by IMO to designate the area as a PSSA.El Sistema Arrecifal Mesoamericano (SAM) es un área natural que se extiende aproximadamente 1,000 km a través de las costas caribeñas de México, Belice, Guatemala y Honduras. A partir de 1997, los gobiernos de estos cuatro países han considerado una iniciativa para que la Organización Marítima Internacional (OMI) designe al SAM como Zona Marítima Especialmente Sensible (ZMES). La justificación para tal designación sería la protección del SAM contra los efectos negativos del tráfico marítimo internacional. Tal designación constituiría también un mecanismo para conservar su biodiversidad y aprovechar sosteniblemente sus recursos. El presente documento proporciona una síntesis del estado actual de la información sobre las características ecológicas, socioeconómicas y de actividades marítimas sobre la porción mexicana del SAM (Quintana Roo), como una contribución al esfuerzo de protección al identificar fortalezas y debilidades en el cumplimiento de las directrices establecidas por la OMI para la designación del área como ZMES

Deltamethrin resistance in Aedes aegypti results in treatment failure in Merida, Mexico

The operational impact of deltamethrin resistance on the efficacy of indoor insecticide applications to control Aedes aegypti was evaluated in Merida, Mexico. A randomized controlled trial quantified the efficacy of indoor residual spraying (IRS) against adult Ae. aegypti in houses treated with either deltamethrin (to which local Ae. aegypti expressed a high degree of resistance) or bendiocarb (to which local Ae. aegypti were fully susceptible) as compared to untreated control houses. All adult Ae. aegypti infestation indices during 3 months post-spraying were significantly lower in houses treated with bendiocarb compared to untreated houses (odds ratio < 0.75; incidence rate ratio < 0.65) whereas no statistically significant difference was detected between the untreated and the deltamethrin-treated houses. On average, bendiocarb spraying reduced Ae. aegypti abundance by 60% during a 3-month period. Results demonstrate that vector control efficacy can be significantly compromised when the insecticide resistance status of Ae. aegypti populations is not taken into consideration

Insecticide-Treated House Screens to Reduce Infestations of Dengue Vectors

The public health importance of the endophilic mosquito Aedes aegypti increased dramatically in the recent decade, because it is the vector of dengue, chikungunya, Zika and yellow fever. The use of long-lasting insecticidal nets (LLINs) fixed on doors and windows, as insecticide-treated screening (ITS), is one innovative approach recently evaluated for Aedes control in South Mexico. From 2009 to 2014, cluster-randomised controlled trials were conducted in Acapulco and Merida. Intervention clusters received Aedes-proof houses (‘Casas a prueba de Aedes’) with ITS and were followed up during 2 years. Overall, results showed significant and sustained reductions on indoor adult vector densities in the treated clusters with ITS after 2 years: ca. 50% on the presence (OR ≤ 0.62, P < 0.05) and abundance (IRR ≤ 0.58, P < 0.05). ITS on doors and windows are ‘user-friendly’ tool, with high levels of acceptance, requiring little additional work or behavioural change by householders. Factors that favoured these interventions were (a) house construction, (b) high coverage achieved due to the excellent acceptance by the community and (c) collaboration of the vector control services; and only some operational complaints relating to screen fragility and the installation process. ITS is a housing improvement that should be part of the current paradigms for urban vector-borne disease control

Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness

Recent findings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the significance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression significantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could finally determine a fast tumor progression in PDAC patients.Fil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Carozzo, A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: May, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Di Siervi, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: de Sousa Serro, Maximiliano Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Yaneff, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Rodriguez Gonzalez, Angela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentin