International consortium for personalized medicine: an international survey about the future of personalized medicine.

Aim: The ICPerMed, international initiative promoting personalized medicine, has realized a survey among a group of experts, to define a common vision for the deployment of personalized medicine across healthcare systems until 2030. Materials & methods: ICPerMed defined five perspectives (p.4) and addressed an online questionnaire to 97 international experts to collect their views. Results: Seventy (72%) of the 97 experts effectively answered the survey from which 69 answers were exploitable. Respondents from a variety of international profiles approved the five proposed perspectives and reported required actions and best practices. Conclusion: There is a large consensus among experts directly involved in shaping international strategies and policies, calling for voluntarist public policies, new IT platforms enabling data-driven approaches, large-scale educational programs and new financing models.

Missed Initial Medical Visits: Predictors, Timing, and Implications for Retention in HIV Care.

HIV disproportionately affects racial/ethnic minorities and individuals living in the southern United States, and missed clinic visits account for much of this disparity. We sought to evaluate: (1) predictors of missed initial HIV medical visits, (2) time to initial visit, and (3) the association between initial visit attendance and retention in HIV care. Chart reviews were conducted for 200 consecutive HIV-infected patients (100 in Dallas, 100 in San Antonio) completing case management (CM) intake. Of these, 52 (26%) missed their initial visit, with 22 (11%) never presenting for care. Mean age was 40 years, 85% were men, >70% were of minority race/ethnicity, and 28% had a new HIV diagnosis. Unemployment (OR [95% CI] = 2.33 [1.04-5.24], p = 0.04) and lower attendance of CM visits (OR = 3.08 [1.43-6.66], p = 0.004) were associated with missing the initial medical visit. A shorter time to visit completion was associated with CD4 ≤ 200 (HR 1.90 [1.25-2.88], p = 0.003), Dallas study site (HR = 1.48 [1.03-2.14], p = 0.04), and recent hospitalization (HR = 2.18 [1.38-3.43], p < 0.001). Patients who did not complete their initial medical visit within 90 days of intake were unlikely to engage in care. Initial medical visit attendance was associated with higher proportion of visits attended (p = 0.04) and fewer gaps in care (p = 0.01). Missed medical visits were common among HIV patients initiating or reinitiating care in Texas. Employment and CM involvement predicted initial medical visit attendance, which was associated with retention in care. New, early engagement strategies are needed to decrease missed visits and reduce HIV health disparities.

Comparison of the interleukin-1ß-inducing potency of allergenic spores from higher fungi (basidiomycetes) in a cryopreserved human whole blood system.

BACKGROUND: Spores from basidiomycete fungi (basidiospores) are highly prevalent in the atmosphere of urban and rural settings. Studies have confirmed their potential to affect human health as allergens. Less is known about their potential to serve as stimuli of the innate immune system and induce proinflammatory reactions. METHODS: In this study, we evaluated the proinflammatory potential of spores from 11 allergenic basidiomycete species (gilled: Pleurotus ostreatus,Oudemansiella radicata,Armillaria tabescens,Coprinus micaceus,Pluteus cervinus, and Chlorophyllum molybdites, and nongilled: Pisolithus arhizus,Merulius tremellosus,Calvatia cyathiformis,Lycoperdon pyriforme, andBoletus bicolor) based on their potency to induce the release of the proinflammatory cytokine interleukin (IL)-1ß in a cryopreserved human whole blood system. In addition, the roles of morphological features of the spores (surface area, shape, and pigmentation) were examined for their role in the IL-1ß-including potency of spores. Peripheral blood from healthy volunteers was collected, pooled, and cryopreserved. After stimulating the cryopreserved pooled blood with 10(6) to 10(3) basidiospores/ml, the concentration of IL-1ß in culture supernatants was determined with ELISA. RESULTS: Basidiospores manifested concentration-dependent IL-1ß-inducing potency, which was more marked among basidiospores from gilled basidiomycetes. At higher concentrations of basidiospores, the IL-1ß-inducing potency could be differentiated in the cryopreserved human whole blood system. Morphological features did not correlate with the IL-1ß-inducing potency of the basidiospores, suggesting that nonmorphological properties modulate the IL-1ß-inducing potency. CONCLUSION: Our data provide evidence of the proinflammatory potential of basidiospores, and the utility of cryopreserved human whole blood as a human-based in vitro system to study the immune reactivity of allergenic basidiospores.

Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test.

Threats of pyrogenicity were discovered more than a century ago. Measures to determine the safety of parenterals and, more recently, medical devices and cell therapies for human use have been in place for 70 years. Currently, there are three testing possibilities available: the Rabbit Pyrogen Test, the Limulus Amebocyte Lysate test (Bacterial Endotoxin Test), and test systems using human whole blood or human monocytes, called Monocyte Activation Test (MAT). The MAT is based on the human fever reaction and thus most closely reflects the human situation. Unfortunately, regulations and testing guidelines are not fully harmonized, despite formal international validation. Furthermore, data showing that the MAT is capable of covering the totality of possible pyrogens relevant to humans were not included in the MAT validations of the last decade. For this review we collate evidence from published literature, unpublished data of our own, and results from the international validation study to show that there is overwhelming scientific evidence to conclude that the whole blood MAT reliably detects non-endotoxin pyrogens. Therefore, further validation exercises do not seem warranted.