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1.  Guideline-Based Peer-to-Peer Consultation Optimizes Pegfilgrastim Use With No Adverse Clinical Consequences 
Journal of Oncology Practice  2012;8(3 Suppl):e14s-e17s.
Active expert peer-to-peer consultation with prescribing oncologists can promote adherence to guidelines and lead to cost reductions without risk of neutropenic fever, with or without hospitalization, for patients with cancer.
Practice guidelines do not recommend the routine use of colony-stimulating factors when there is a low risk (< 10%) of febrile neutropenia (FN). We prospectively determined whether expert peer-to-peer consultation with prescribing oncologists would improve adherence to guidelines and whether there would be any adverse events associated with that adherence.
Commencing in March 2010, we reviewed requests for pegfilgrastim from 22 community oncology practices comprising 78 physicians providing service to approximately 97,000 Medicare members. Paid claims data on all chemotherapy and supportive care medications were reviewed from fourth quarter (Q4) 2009 through third quarter (Q3) 2010. In total, 82 patients received pegfilgrastim. If the prescribed chemotherapy was associated with a low risk (< 10%) for FN, then a peer review was initiated. The treating physician made the final decision to use, or not use, pegfilgrastim, and no denials were issued.
A total of 245 units (1 unit = 6 mg) of pegfilgrastim were administered during the four quarters analyzed. Use in the low-risk category decreased from 52 units in Q4 2009 to 15 units in Q3 2010. The per-member per-month (PMPM) cost of pegfilgrastim decreased across quarters, with an average cost of $1.07 PMPM for Q4 2009 and $0.57 PMPM for Q3 2010. No studied patient was admitted for neutropenic fever.
Active expert peer-to-peer consultation with prescribing oncologists can promote adherence to guidelines and potentially lead to significant cost reductions without significant risk of neutropenic fever, with or without hospitalization, for patients with cancer.
PMCID: PMC3348596  PMID: 22942828
2.  Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature 
PLoS Pathogens  2012;8(4):e1002647.
Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-β; IL-1β; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses.
Author Summary
Salmonellosis continues to compromise human health, animal welfare, and modern agriculture. Developing a comprehensive control plan requires an understanding of how pathogens emerge and express traits that confer increased incidence and severity of disease. It is well-established that animal passage often results in increased virulence; however, our findings indicate that the capacity to undergo a pronounced increase in virulence after passage was much more prevalent in certain Salmonella isolates than in others. The resultant hyperinfectious strains are among the most virulent salmonellae reported; were restricted to certain serotypes; and were able to override the immunity conferred in vaccinated animals. The induction of hypervirulence was responsive to subtle changes in environmental conditions and, potentially, may occur in other salmonellae serotypes after passage through certain hosts and/or exposure to certain environmental variables; a response that may be common across the microbial realm. Thus, management practices and environmental conditions inherent to livestock production have the potential to inadvertently trigger hypervirulence (e.g., diet; herd size; exposure to livestock waste and/or antimicrobials). From a farm management perspective, careful consideration must be given to risk-management strategies that reduce emergence/persistence of these potential food-borne contaminants to safeguard public health and reduce industry-associated losses.
PMCID: PMC3325197  PMID: 22511871
3.  Antiestrogen therapy in recurrent ovarian cancer resulting in 28 months of stable disease: a case report and review of the literature 
Hormonal therapy for adjuvant treatment of ovarian cancer may provide a low toxicity option in some patients with refractory disease. A 53 year-old patient with stage IIIC papillary serous ovarian cancer previously treated with multiple chemotherapy regimens with platinum-resistant disease was treated with antiestrogen therapy for 28 months before requiring reinstitution of cytotoxic chemotherapy. Hormonal therapy may be effective in a subset of epithelial ovarian cancer patients with endocrine sensitivity and should be considered in the treatment of platinum-resistant patients.
PMCID: PMC3147280  PMID: 21814300
Ovarian Neoplasms; Antineoplastic Agents; Hormonal; Selective Estrogen Receptor Modulators; Tamoxifen; Aromatase
4.  Human Salmonella Clinical Isolates Distinct from Those of Animal Origin▿  
The global trend toward intensive livestock production has led to significant public health risks and industry-associated losses due to an increased incidence of disease and contamination of livestock-derived food products. A potential factor contributing to these health concerns is the prospect that selective pressure within a particular host may give rise to bacterial strain variants that exhibit enhanced fitness in the present host relative to that in the parental host from which the strain was derived. Here, we assessed 184 Salmonella enterica human and animal clinical isolates for their virulence capacities in mice and for the presence of the Salmonella virulence plasmid encoding the SpvB actin cytotoxin required for systemic survival and Pef fimbriae, implicated in adherence to the murine intestinal epithelium. All (21 of 21) serovar Typhimurium clinical isolates derived from animals were virulent in mice, whereas many (16 of 41) serovar Typhimurium isolates derived from human salmonellosis patients lacked this capacity. Additionally, many (10 of 29) serovar Typhimurium isolates derived from gastroenteritis patients did not possess the Salmonella virulence plasmid, in contrast to all animal and human bacteremia isolates tested. Lastly, among serovar Typhimurium isolates that harbored the Salmonella virulence plasmid, 6 of 31 derived from human salmonellosis patients were avirulent in mice, which is in contrast to the virulent phenotype exhibited by all the animal isolates examined. These studies suggest that Salmonella isolates derived from human salmonellosis patients are distinct from those of animal origin. The characterization of these bacterial strain variants may provide insight into their relative pathogenicities as well as into the development of treatment and prophylactic strategies for salmonellosis.
PMCID: PMC2268321  PMID: 18245251

Results 1-4 (4)