Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

An economic analysis of SPAM law

In this paper, I develop an economic argument for regulating the sending of junk emails, and examine the efficiency of various approaches to regulate junk emails. The first part of the paper develops an externality model of spam to show that in the absence of regulation, junk emails are inefficient. Next, I analyse the regulatory approaches presently used in the United States in three categories: opt-out, filtering and blocking, and opt-in. The study finds that spam can be both a positive externality as well as a negative one. However, the likelihood of being a negative externality is more probable. Absence regulation, no allocation of a property right to spam leads to an efficient level of spam. An examination of the three categories show that only the opt-in approach ensures that there is no net social loss, but not necessarily at a socially efficient level of spam. Hence, it is only a second best solution. Based on the conclusions that opt-in is the best solution given the constraints of transaction cost, the paper suggests a set of policy conclusions that serve as guidelines for countries enacting laws to regulate junk emails or spam

Copyright Failure and the Protection for Tables and Compilation

Current copyright laws in all jurisdictions are lacking explicit provisions for protecting many types of contemporary art. It remains unclear to what extent ideas should be copyrightable as art, if at all; or whether an artwork’s commercial nature provides a decisive factor regarding appropriation. Certain situations seem plainly inappropriate, such as artists needing to seek legal counsel in conjunction with creating their artwork: inappropriate in its financial extravagance and in its inevitable curb on creativity. As such, it is incumbent upon courts and legislatures to analyze the issue and to provide guidance. It is the author’s finding that strong moral rights and a vibrant public domain are not necessarily at odds with each other, especially when parties are open to communication. Laws operate to provide structure when parties do not make other arrangements amongst themselves; contracts between artists and galleries, artists and publishers, even artists and other artists may provide the highest degree of satisfaction for specific parties to a specific situation. Not surprisingly, parties with legal or business interests in art and parties with artistic interests in art would communicate better if they understood each other’s situations. Hopefully the issues will continue to be the focus of some thought on all platforms such that informed legal decisions can be made and artists can pursue and protect their creative productions, no matter their format

On Training Law and Economics Scholarship in the Legal Academia

Although law and economics is considered to be enjoying significant success and influence in the United States, particularly in American law schools, its reception elsewhere is at most tepid. In this paper, I suggest that this sorry state of affairs is due to the lack of economic literacy skills among legal scholars, which in turn is due to the legal and economic education systems in Europe and in other countries following a similar structure. Some evidence of the importance of competency in these economic literacy skills for success in law and economics scholarship is offered by way of analysis of journal editorships as a proxy for success. Furthermore, the effectiveness of various law and economics programmes are discussed and the establishment of doctoral programmes in law and economics within the legal academia as a solution to the problem of law and economics scholarship is examined.