Browsing by Subject "resistance"
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Item Open Access First-line treatment of metastatic melanoma: role of nivolumab.(Immunotargets Ther, 2017) Force, Jeremy; Salama, April KsHistorically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes.Item Open Access Global Trends in Typhoid and Paratyphoid Fever(2010) Crump, John A; Mintz, Eric DTyphoid and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and Southeast Asia, where enteric fever is associated with poor sanitation and unsafe food and water. High-quality incidence data from Asia are underpinning efforts to expand access to typhoid vaccines. Efforts are underway to develop vaccines that are immunogenic in infants after a single dose and that can be produced locally in countries of endemicity. The growing importance of Salmonella enterica serotype Paratyphi A in Asia is concerning. Antimicrobial resistance has sequentially emerged to traditional first-line drugs, fluoroquinolones, and third-generation cephalosporins, posing patient treatment challenges. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The availability of full genome sequences for S. enterica serotype Typhi and S. enterica serotype Paratyphi A confirms their place as monomorphic, human-adapted pathogens vulnerable to control measures if international efforts can be redoubled.Item Open Access Lessons Learned from the Anaerobe Survey: Historical Perspective and Review of the Most Recent Data (2005-2007)(2010) Snydman, David R; Jacobus, Nilda V; McDermott, Laura A; Golan, Yoav; Hecht, David W; Goldstein, Ellie JC; Harrell, Lizzie; Jenkins, Stephen; Newton, Duane; Pierson, Carl; Rihs, John D; Yu, Victor L; Venezia, Richard; Finegold, Sydney M; Rosenblatt, Jon E; Gorbach, Sherwood LBackground. The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species. Methods. Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations. Results. The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii (similar to 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period. Conclusions. In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.Item Open Access Sportswashing: Complicity and Corruption(Sport, Ethics and Philosophy) Fruh, Kyle; Archer, Alfred; Wojtowicz, JakeWhen the 2022 FIFA Men’s World Cup was awarded to Qatar, it raised a number of moral concerns, perhaps the most prominent of which was Qatar’s woeful record on human rights in the arena of migrant labour. Qatar’s interest in hosting the event is aptly characterised as a case of ‘sportswashing’. The first aim of this paper is to provide an account of the nature of sportswashing, as a practice of using an association with sport, usually through hosting an event or owning a club (such as Newcastle United, owned by Saudi Arabia), to subvert the way that others attend to a moral violation for which the sportswashing agent is responsible. This may be done through distracting away from wrongdoing, minimising it, or normalising it. Second, we offer an account of the distinctive wrongs of sportswashing. The gravest moral wrong is the background injustice which sportswashing threatens to perpetuate. But the distinctive wrongs of sportswashing are twofold: first, it makes participants in sport (athletes, coaches, journalists, fans) complicit in the sportswasher’s wrongdoing, which extends a moral challenge to millions of people involved with sport. Second, sportswashing corrupts valuable heritage associated with sporting traditions and institutions. Finally, we examine how sportswashing ought to be resisted. The appropriate forms of resistance will depend upon different roles people fill, such as athlete, coach, journalist, fan. The basic dichotomy of resistance strategies is to either exit the condition of complicity, for example by refusing to participate in the sporting event, or to modify one’s engagement with the goal of transformation in mind. We recognize this is difficult and potentially burdensome: sports are an important part of many of our lives; our approach attempts to respect this.