Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient

Background: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive, neurodegenerative disease and most patients affected die of respiratory compromise and/or pneumonia within 2â3 years of diagnosis. As ALS progresses, ventilator assistance is required. In the end stages of the disease, patients suffer from respiratory failure and may become ventilator-dependent. Deaths due to malfunction of mechanical ventilators are reported but there are very few forensic autopsy records. We report the case of a 69-year-old ALS female ventilator-dependent, trachostomised patient who was found dead by her husband, with the ventilator in âstand-byâ mode. Method: A forensic autopsy was performed. Samples of internal organs were taken for histological and toxicological examination. The ventilator internal memory was also analysed and tested in order to find possible malfunction. Results: Gross examination did not reveal any sign of trauma but showed brain and lung congestion. Pulmonary histological examination revealed thickening of peribronchial interstitial space, alveolar over-distension, break of inter-alveolar walls and diffuse alveolar haemorrhages. Focal microhemorrhages were also detected in other organs. Analysis of the ventilator internal memory showed that during the night of death, there had been several voltage drops. Specific tests revealed malfunction of the internal battery which was unable to provide the necessary voltage, as a consequence the ventilator switched off, stopping ventilation. Battery malfunction reduced the volume of the ventilator alarm, which was not heard by the caregiver. Conclusion: Histological pattern, with acute pulmonary emphysema and focal polivisceral haemorrhages, is strongly suggestive of a death due to âacuteâ asphyxia. The authors also discuss the need for strict supervision and follow up of these ventilatory dependent patients and their devices. Resumo: Introdução: A Esclerose Lateral Amiotrófica (ELA) é uma doença fatal, progressiva e neurodegenerativa e a maioria dos doentes afectados morrerão de falha respiratória e/ou pneumonia 2 ou 3 anos após o diagnóstico. à medida que a ELA progride torna-se necessária a assistência ventilatória. Nos estágios finais da doença, os doentes sofrem de insuficiência respiratória e podem tornar-se dependentes do ventilador. São conhecidas mortes devido ao mau funcionamento de ventiladores mecânicos mas existem poucos registos forenses de tal situação. Relatamos o caso de uma doente de 69 anos com ELA, traqueostomizada e dependente do ventilador, que foi encontrada morta pelo seu marido com o ventilador em modo de espera («stand-by»). Método: Foi realizada uma autópsia forense. Foram recolhidas amostras dos órgãos internos para exame toxicológico e histológico. A memória interna do ventilador foi também analisada e testada de modo a descobrir uma possível avaria. Resultados: O exame macroscópico não revelou qualquer sinal de trauma mas indicou congestão cerebral e pulmonar. O exame pulmonar histológico revelou o espessamento do espaço intersticial peribrônquico, sobredistensão alveolar, quebra de paredes interalveolares e hemorragias alveolares difusas. Foram detetadas micro-hemorragias focais noutros órgãos. A análise da memória interna do ventilador mostrou que, durante a noite da morte, houve diversas quedas de tensão. Testes específicos revelaram o mau funcionamento da bateria interna que não conseguiu fornecer a tensão necessária, consequentemente o ventilador desligou-se, parando a ventilação. O mau funcionamento da bateria reduziu o volume do alarme do ventilador, que não foi ouvido pelo prestador de cuidados. Conclusão: O padrão histológico, com enfisema pulmonar agudo e hemorragias focais poliviscerais, é fortemente indicador de morte devido a asfixia «aguda». Os autores discutem também a necessidade de uma supervisão rigorosa e seguimento destes doentes dependentes do ventilador e dos seus equipamentos. Keywords: Amyotrophic lateral sclerosis, Acute respiratory failure, Home mechanical ventilation, Palavras-chave: Esclerose lateral amiotrófica, Insuficiência respiratória aguda, Ventilação mecânica doméstic

Electric field effects on the dynamics of bubble detachment from an inclined surface

An experimental apparatus to study bubble detachment from an inclined surface under the action of electric forces is described. It consists of a container filled with FC72 at room temperature and pressure where a train of gas bubbles is injected from an orifice. An electrostatic field can be imposed around the bubble, while the cell can be tilted from 0 to 90°. It is possible to study interface growth with the aid of high-speed cinematography. Since the interface is asymmetrical, a mirror system allowed to acquire, in the same frame, two images at 90° of the bubble. Different inclinations, injection rates and voltages were tested in order to couple the effects of shear gravity and electric field. Curvature and contact angles have been derived with appropriate interpolation methods of the profile. Force balances on the bubble were checked, finding an electric force, which, at first pulls the bubbles from the orifice, then pushes it against the surface. The motion of the center of gravity confirms this behaviour. A power balance has been developed to determine the energy contributions, revealing that surface growth incorporates both the effects of inlet power and electric field

System Reliability Evaluation Using Concurrent Multi-Level Simulation of Structural Faults

This paper provides a methodology that leverages state-of-the-art techniques for efficient fault simulation of structural faults together with transaction level modeling. This way it is possible to accurately evaluate the impact of the faults on the entire hardware/software syste

Efficient Simulation of Structural Faults for the Reliability Evaluation at System-Level

In recent technology nodes, reliability is considered a part of the standard design ¿ow at all levels of embedded system design. While techniques that use only low-level models at gate- and register transfer-level offer high accuracy, they are too inefficient to consider the overall application of the embedded system. Multi-level models with high abstraction are essential to efficiently evaluate the impact of physical defects on the system. This paper provides a methodology that leverages state-of-the-art techniques for efficient fault simulation of structural faults together with transaction-level modeling. This way it is possible to accurately evaluate the impact of the faults on the entire hardware/software system. A case study of a system consisting of hardware and software for image compression and data encryption is presented and the method is compared to a standard gate/RT mixed-level approac

Digital, memory and mixed-signal test engineering education: five centres of competence in Europe

The launching of the EuNICE-Test project was announced two years ago at the first DELTA Conference. This project is now completed and the present paper describes the project actions and outcomes. The original idea was to build a long-lasting European Network for test engineering education using both test resource mutualisation and remote experiments. This objective is fully fulfilled and we have now, in Europe, five centres of competence able to deliver high-level and high-specialized training courses in the field of test engineering using a high-performing industrial ATE. All the centres propose training courses on digital testing, three of them propose mixed-signal trainings and three of them propose memory trainings. Taking into account the demand in test engineering, the network is planned to continue in a stand alone mode after project end. Nevertheless a new European proposal with several new partners and new test lessons is under construction

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Outpatient prescription writing quality in a paediatric general hospital

Introduction The writing of prescriptions is an important aspect of medical practice. Since 2006, the Swiss authorities have decided to impose incentives to prescribe generic drugs. The objectives of this study were 1) to determine the evolution of the outpatient prescription practice in our paediatric university hospital during 2 periods separated by 5 years; 2) to assess the writing quality of outpatient prescriptions during the same period.Materials & Methods Design: Copies of prescriptions written by physicians were collected twice from community pharmacies in the region of our hospital for a 2-month period in 2005 and 2010. They were analysed according to standard criteria regarding both formal and pharmaceutical aspects. Drug prescriptions were classified as a) complete when all criteria for safety were fulfilled, b) ambiguous when there was a danger of a dispensing error because of one or more missing criteria, or c) containing an error.Setting: Paediatric university hospital.Main outcome measures: Proportion of generic drugs; outpatient prescription writing quality.Results: A total of 651 handwritten prescriptions were reviewed in 2005 and 693 in 2010. They contained 1570 drug prescriptions in 2005 (2.4 ± 1.2 drugs per patient) and 1462 in 2010 (2.1 ± 1.1). The most common drugs were paracetamol, ibuprofen, and sodium chloride. A higher proportion of drugs were prescribed as generic names or generics in 2010. Formal data regarding the physicians and the patients were almost complete, except for the patients' weight. Of the drug prescriptions, 48.5% were incomplete, 11.3% were ambiguous, and 3.0% contained an error in 2005. These proportions rose to 64.2%, 15.5% and 7.4% in 2010, respectively.Discussions, Conclusion This study showed that physicians' prescriptions comprised numerous omissions and errors with minimal potential for harm. Computerized prescription coupled with advanced decision support is eagerly awaited.Disclosure of Interest None Declare

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Outpatient prescriptions practice and writing quality in a paediatric university hospital.

BACKGROUND: The writing of prescriptions is an important aspect of medical practice. This activity presents some specific problems given a danger of misinterpretation and dispensing errors in community pharmacies. The objective of this study was to determine the evolution of the prescription practice and writing quality in the outpatient clinics of our paediatric university hospital.¦METHODS: Copies of prescriptions written by physicians were collected from community pharmacies in the region of our hospital for a two-month period in 2005 and 2010. They were analysed according to standard criteria, including both formal and pharmaceutical aspects.¦RESULTS: A total of 597 handwritten prescriptions were reviewed in 2005 and 633 in 2010. They contained 1,456 drug prescriptions in 2005 and 1,348 in 2010. Fifteen drugs accounted for 80% of all prescriptions and the most common drugs were paracetamol and ibuprofen. A higher proportion of drugs were prescribed as International Nonproprietary Names (INN) or generics in 2010 (24.7%) compared with 2005 (20.9%). Of the drug prescriptions examined, 55.5% were incomplete in 2005 and 69.2% in 2010. Moreover in 2005, 3.2% were legible only with difficulty, 22.9% were ambiguous, and 3.0% contained an error. These proportions rose respectively to 5.2%, 27.8%, and 6.8% in 2010.¦CONCLUSION: This study showed that fifteen different drugs represented the majority of prescriptions, and a quarter of them were prescribed as INN or generics in 2010; and that handwritten prescriptions contained numerous omissions and preventable errors. In our hospital computerised prescribing coupled with advanced decision support is eagerly awaited