Liability, Regulation and Policy in Surgical Innovation: The Cutting Edge of Research and Therapy

This article examines the implications of the foregoing competing claims from a U.S. legal perspective, focusing particularly on how the legal system addresses patient safety concerns and autonomous decision-making of surgeons in the context of surgical innovation. The lack of oversight and the risks borne by patients during surgeons\u27 development and subsequent refinement of a novel procedure must be balanced with the need to encourage medical progress through the development of improved techniques designed to benefit the health of current and future patients. This article argues that current reliance on the medical malpractice system and the federal regulatory system of oversight of human subjects research is inadequate in appropriately balancing patient safety and medical progress. The deficiencies in relying on the current approaches are further highlighted in a legal review and case study analysis of one surgical innovation that stimulated a wave of legal claims in the 1990s. A comprehensive legal analysis ultimately leads to a critique of current policy approaches and the recommendation of a three-pronged policy approach distinctly tailored to surgical innovation, which includes monitoring, local institutional oversight, and educational initiatives. As will be observed, complicating this examination is the cultural context in which surgical innovation takes place, lack of consensus about the appropriate treatment of surgical innovation, and the wide variation in procedures that could conceivably fall within a definition of surgical innovation. Part I of this article briefly examines the practice and culture of surgical innovation, describing the high value placed on innovation and professional autonomy and the definitional challenge in characterizing innovative surgery. Part II introduces the two currently available alternate legal pathways relevant to concerns for patient safety—the medical practice pathway and the human subjects research pathway—and describes the surgeon\u27s critical role in determining the pathway. Part III discusses the medical practice pathway and the conclusions that can be drawn from the law on point, particularly in the areas of negligence and informed consent, and analyzes their implications for the treatment of innovative surgery. Part IV describes the human subjects research pathway in detail. It begins with a discussion of the federal system of regulatory oversight and protection, its history and potential application to innovative surgery. It continues by examining the potential cause of action for research negligence, followed by conclusions and implications for the treatment of innovative surgery. Part V analyzes and extracts lessons from one example of surgical innovation, its legal pathways and malpractice history. Lastly, this article concludes by examining some of the legal implications of current policy approaches and ultimately recommends a distinct approach designed to balance medical progress with greater accountability and opportunities for improved patient safet

HIV-associated progressive multifocal leukoencephalopathy. Current perspectives

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, caused by the polyomavirus JC and occurring almost exclusively in the context of severe immune depression. AIDS represents the most common predisposing condition for PML development. Antiretroviral treatment has reduced PML incidence in HIV-infected subjects, but the disease remains a severe and life-threatening complication of AIDS, considering thus far the lack of an effective anti-JC virus (JCV) direct-acting antiviral drug. In the last decade, the use of monoclonal antibodies for treating immune-based diseases evidenced new predisposing conditions for PML development, promoting a renewed interest in PML pathogenesis. In this article, we review the current knowledge on JCV epidemiology and AIDS-associated PML incidence, JCV viral cycle, pathogenesis, and the interplay with HIV infection. We give an updated overview of diagnostic and prognostic tools available for PML diagnosis and describe past and current therapeutic approaches, including new strategies for PML cure

Reducing the operational cost of cloud data centers through renewable energy

The success of cloud computing services has led to big computing infrastructures that are complex to manage and very costly to operate. In particular, power supply dominates the operational costs of big infrastructures, and several solutions have to be put in place to alleviate these operational costs and make the whole infrastructure more sustainable. In this paper, we investigate the case of a complex infrastructure composed of data centers (DCs) located in different geographical areas in which renewable energy generators are installed, co-located with the data centers, to reduce the amount of energy that must be purchased by the power grid. Since renewable energy generators are intermittent, the load management strategies of the infrastructure have to be adapted to the intermittent nature of the sources. In particular, we consider EcoMultiCloud, a load management strategy already proposed in the literature for multi-objective load management strategies, and we adapt it to the presence of renewable energy sources. Hence, cost reduction is achieved in the load allocation process, when virtual machines (VMs) are assigned to a data center of the considered infrastructure, by considering both energy cost variations and the presence of renewable energy production. Performance is analyzed for a specific infrastructure composed of four data centers. Results show that, despite being intermittent and highly variable, renewable energy can be effectively exploited in geographical data centers when a smart load allocation strategy is implemented. In addition, the results confirm that EcoMultiCloud is very flexible and is suited to the considered scenario

Psychoactive drug advertising: analysis of scientific information

OBJECTIVE: According to the World Health Organization, medicinal drug promotion should be reliable, accurate, truthful, informative, balanced, up-to-date and capable of substantiation. The objective of the present study was to review psychoactive drug advertisements to physicians as for information consistency with the related references and accessibility of the cited references. METHODS: Data was collected in the city of Araraquara, Southeastern Brazil, in 2005. There were collected and reviewed 152 drug advertisements, a total of 304 references. References were requested directly from pharmaceutical companies' customer services and searched in UNESP (Ibict, Athenas) and BIREME (SciELO, PubMed, free-access indexed journals) library network and CAPES journals. Advertisement statements were checked against references using content analysis. RESULTS: Of all references cited in the advertisements studied, 66.7% were accessed. Of 639 promotional statements identified, 346 (54%) were analyzed. The analysis showed that 67.7% of promotional statements in the advertisements were consistent with their references, while the remaining was either partially consistent or inconsistent. Of the material analyzed, an average 2.5 (1-28) references was cited per advertisement. In the text body, there were identified 639 pieces of information clearly associated with at least one cited reference (average 3.5 pieces of information per advertisement). CONCLUSIONS: The study results evidenced difficult access to the references. Messages on efficacy, safety and cost, among others, are not always supported by scientific studies. There is a need for regulation changes and effective monitoring of drug promotional materials.OBJETIVO: Segundo a Organização Mundial da Saúde, as propagandas de medicamentos devem ser fidedignas, exatas, verdadeiras, informativas, equilibradas, atualizadas e passíveis de comprovação. O objetivo do estudo foi avaliar as propagandas de medicamentos psicoativos divulgadas a médicos, em relação à concordância das informações contidas nas peças publicitárias com as suas respectivas referências bibliográficas e à acessibilidade dessas referências citadas. MÉTODOS: A coleta de dados foi realizada durante o ano de 2005, em Araraquara, SP. Foram coletadas e analisadas propagandas de 152 medicamentos, num total de 304 referências. As referências bibliográficas foram solicitadas aos serviços de atendimento ao cliente dos laboratórios e consultadas nas bibliotecas da rede UNESP (Ibict, Athenas), BIREME (SciELO, PubMed, periódicos catalogados de acesso livre) e periódicos CAPES. As afirmações das propagandas foram conferidas com as das referências por meio da técnica de análise de conteúdo. RESULTADOS: Das referências citadas nas propagandas, 66,7% foram acessadas. De 639 afirmações identificadas, foi possível analisar 346 (54%). Verificou-se que 67,7% das afirmações das propagandas conferiam com suas referências e as demais não conferiam ou conferiam parcialmente. Entre as propagandas analisadas, foi observada média de 2,5 (1-28) referências citadas por propaganda. No corpo das propagandas, foram identificadas 639 informações que estavam explicitamente associadas à pelo menos uma das referências citadas (média de 3,5 informações por propaganda). CONCLUSÕES: Os resultados evidenciaram a dificuldade de acesso às referências. As mensagens de eficácia, segurança, custos, entre outras, nem sempre estão respaldadas por estudos científicos. São necessárias mudanças nas exigências legais e fiscalização efetiva das promoções de medicamentos.Universidade Estadual Paulista Júlio Mesquita Faculdade de Ciências Farmacêuticas. Departamento de Fármacos e MedicamentosUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicobiologiaUNIFESP, EPM, Depto. de PsicobiologiaSciEL

Load Management with Predictions of Solar Energy Production for Cloud Data Centers

Power supply of big infrastructures is today a tremendous operational cost for providers and the expected growth of Internet traffic and services will lead to a further expansion of the computing and networking infrastructures and this, in its turn, raises also concerns in terms of sustainability. In this context, renewable energy generators can help to both reduce costs and alleviate the concerns of sustainability of big infrastructures. In this paper, we consider the case of Data Centers (DCs) composed of a few sites located in different geographical positions and powered with solar energy. Due to the intermittent nature of solar energy, different time zones and price of electricity in different locations, load management strategies are fundamental. We consider predictions of the solar energy production performed through Artificial Neural Networks and we assess the impact of predictions on load management decisions and, ultimately, on the DC performance

Persistent systemic microbial translocation, inflammation, and intestinal damage during Clostridioides difficile infection

Background. Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods. Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results. Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions. CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated

Defective production of interferon-γ and tumour necrosis factor-α by AIDS mononuclear cells after in vitro exposure to Rhodococcus equi

The production of interferon-γ and tumour necrosis factor-α was evaluated in the peripheral blood mononuclear cells (PBMCs) from healthy donors and AIDS patients after Rhodococcus equi infection in vitro. PBMCs from healthy donors secreted elevated levels of IFN-γ and TNF-α when challenged in vitro with killed R. equi, whereas the release of both cytokines was impaired in supernatant cultures from AIDS patients. We conclude that the failure of IFN-γ generation in AIDS patients in response to R. equi is not antigen-specific but it may reflect the global impairment of T-cell function. In such patients, however, the infection with R. equi, a facultative intracellular pathogen which survives and replicates within macrophages, may be responsible for the impairment in the TNF-α release, possibly enhancing the HIV-induced macrophage dysftmction