Replication of cowpox virus in macrophages is dependent on the host range factor p28/N1R.

Zoonotic orthopoxvirus infections continue to represent a threat to human health. The disease caused by distinct orthopoxviruses differs in terms of symptoms and severity, which may be explained by the unique repertoire of virus factors that modulate the host's immune response and cellular machinery. We report here on the construction of recombinant cowpox viruses (CPXV) which either lack the host range factor p28 completely or express truncated variants of p28. We show that p28 is essential for CPXV replication in macrophages of human or mouse origin and that the C-terminal RING finger domain of p28 is necessary to allow CPXV replication in macrophages.

Patients' and nurses' preferences for autoinjectors for rheumatoid arthritis: results of a European survey.

PURPOSE: This survey investigated patients' and nurses' preferences among four different autoinjectors used for subcutaneous delivery of medication for rheumatoid arthritis (RA). METHODS: In a multinational survey in five countries, 200 patients with RA and 100 nurses training patients on the use of autoinjectors participated in face-to-face interviews. Respondents were asked to rate the importance of eleven autoinjector attributes and to compare the autoinjectors for etanercept (Enbrel®, MyClic® autoinjector), adalimumab (Humira®, Humira pen), and an etanercept biosimilar (Benepali®, Molly® autoinjector) with a demonstration autoinjector for a new etanercept biosimilar - Erelzi® (SensoReady® autoinjector). RESULTS: Easy grip and ease of performing self-injection were the most important attributes identified by both groups. Overall, 79% of the patients rated the SensoReady autoinjector easier to use than their currently used injection device (86% of MyClic users, 84% of Humira pen users, and 63% of Molly users). In the patient survey, the SensoReady performed better than the other autoinjectors on the attributes visual feedback after completion of injection, easy to grip, and convenient shape. Nurses also rated the SensoReady easier to use than the MyClic (95%), Humira pen (97%), or Molly (91%). When asked which autoinjector they would recommend to a patient with RA who had not used an autoinjector before, 81% of patients and 90% of nurses selected the SensoReady. CONCLUSION: Both patients and nurses perceived the SensoReady to be easier to use compared with other available injection devices. The main reasons for this preference were the buttonless injection, 360° viewing window for feedback (visual confirmation of dose injection), and convenient triangular shape making the injection device easy to grip. Patients and nurses were most likely to recommend the SensoReady autoinjector over other autoinjectors to patients with RA.

Patient preferences in the treatment of hemophilia A: impact of storage conditions on product choice.

OBJECTIVES: To gain insights into the usage of factor VIII (FVIII) products by patients diagnosed with moderate/severe hemophilia A, and to assess the impact and perceived importance of product storage. METHODS: In this study, 200 patients diagnosed with moderate or severe hemophilia A across seven countries participated. Data were collected via a 30-minute, face-to-face interview in six countries and via a web-based survey in the seventh country. The questionnaire evaluated the effect of six features associated with FVIII products on the choice of the product; the structure and flow of data collection was designed to eliminate potential bias. RESULTS: Two-thirds of the respondents were using recombinant FVIII products. Only 17% were generally dissatisfied with current FVIII products, whereas >40% of the respondents were dissatisfied with frequency of administration and storage issues when traveling. The majority noted restrictions in their daily activities, particularly travel and sports. Most of them (85%), stored their product in the refrigerator and of these, 88% believed that it should always be stored there. These patients were also less satisfied with the product overall, more concerned about storage temperature, more restricted in daily activities, and spent more time on preparation and injection compared with patients who stored their product at room temperature. Conjoint analysis revealed that origin of FVIII (plasma-derived vs recombinant) was the strongest driver of product choice among all respondents, followed by storage flexibility (temperature), reconstitution device, and administration frequency. In this study, we did not investigate the efficacy and safety of the product. CONCLUSION: Not refrigerating FVIII products was associated with greater patient satisfaction and less restriction on daily activities. If efficacy and safety are unaffected, then storing FVIII at room temperature might have a positive impact on product choice. Few patients were aware that FVIII can be stored without refrigeration, suggesting that health care professionals who treat hemophilia should communicate this aspect to the patient (depending on the labeled option); this approach might offer patients greater flexibility when traveling and require less time for reconstitution.

A survey of patient and physician acceptance of skin toxicities from anti-epidermal growth factor receptor therapies.

BACKGROUND: Inhibition of the epidermal growth factor receptor (EGFR) extends patient survival in multiple tumor types. Skin toxicities are the most common adverse event (AE) elicited by EGFR inhibitors. Here, we provide deeper insights into patients' and physicians' acceptance of the risk/benefit trade-offs of skin toxicities during cancer therapy, including comparison of their perceptions and experiences with dermatologic AEs. METHODS: A multinational survey of 195 patients and 120 physicians was conducted to gauge attitudes regarding skin toxicities as an AE during cancer therapy. RESULTS: Skin toxicities were identified by patients and physicians as the AE that is most discouraging to patients when undergoing cancer therapies. Skin toxicities were cited as causing pain, impairing quality of life, and proving difficult to manage. Despite these negative influences, the majority of patients (71%) indicated they were willing to accept skin toxicities as an AE of an effective therapy. Indeed, the majority of patients and physicians preferred a more effective therapy that induces more severe skin toxicities than a less efficacious therapy that induces less severe skin toxicities; interestingly, patients were willing to accept a higher likelihood of severe skin toxicities than physicians. CONCLUSION: In this examination of patients' perspectives, we found that patients were willing to accept skin toxicities if they were the anticipated byproduct of a more effective therapeutic regimen. Important differences were observed between patients' and physicians' attitudes regarding risk/benefit trade-offs during cancer therapy, suggesting that patient's considerations and shared decision-making are key to cancer care.

Dermatologic events from EGFR inhibitors: the issue of the missing patient voice.

PURPOSE: As epidermal growth factor receptor (EGFR) inhibitors are associated with a variety of dermatologic adverse events (dAEs), the purpose of this study was to develop an overview of current knowledge of dAEs associated with EGFR inhibitors and to identify knowledge gaps regarding incidence, treatment, impact on quality of life (QOL), and patient acceptance. METHOD: A structured literature search was conducted using MEDLINE/PubMed (January 1983 to January 2014). In total, 71 publications published from 2004 to 2014 were identified for consideration in the final evidence review. RESULTS: The majority of published articles concentrate on the incidence of skin reactions, duration, treatment, and prevention strategies. Different grading systems based on the symptoms of skin rash or on health-related QOL (HRQOL) are used. An additional topic is the possible correlation between acneiform rash and efficacy of EGFR inhibitors. Knowledge gaps identified in the literature were how dAEs impact QOL compared with other AEs from a patient's perspective, patients' acceptance of dAEs (willingness to tolerate), and the impact of physician-patient communication on treatment decisions. CONCLUSIONS: Research is needed on the impact of dAEs on patients' acceptance of cancer treatments. Systematic studies are missing that compare the impact of dAEs with other toxicities on therapy decisions from both physician's and patient's view, and that investigate the balance between efficacy and avoidance of acneiform rash in treatment decisions. Such studies could provide deeper insights into the acceptance of the risk of untoward dermatologic events by both physicians and patients when treating advanced cancers.

Cryopreservation of cellular products in a closed-bag system with an incorporated dimethyl sulfoxide-resistant sterile filter outside of cleanroom facilities.

BACKGROUND: Manipulations, for example, cryopreservation, of cellular therapeutics carried out in an open system must be performed in a class A environment with surrounding class B environment. To avoid cleanroom facilities, a new closed-bag system with an incorporated dimethyl sulfoxide-resistant sterile filter for cryopreservation of cellular products was evaluated at two different centers. STUDY DESIGN AND METHODS: A total of 44 different products (22 buffy coats [BCs] and 22 leukapheresis [LK] products) were split and cryopreserved in parallel in cleanroom facilities (Method I) and with the closed system on the bench of a "normal" laboratory (Method II). Viability analyzed by 7-aminoactinomycin D staining and flow cytometric analysis and sterility of the products were analyzed. RESULTS: Independent of the cellular source (BC or LK), the median viability of CD45+ cells decreased significantly (p < 0.01) during cryopreservation: namely, in BCs, -15.8 percent with both methods, and in LK products, -5.4 percent with Method I and -4.8 percent with Method II, respectively. CD3+ as well as CD14+ cells exhibited a similar pattern and were also found significantly (p < 0.01) diminished after thawing independent of the handling system. For CD19+ cells, the small decrease of viability was only for the BC group significant (p = 0.027) when the cells had been processed with Method I. No bacterial contamination was detected neither in fresh products nor in products after cryopreservation. CONCLUSION: The closed system for cryopreservation of cellular products appears to be equivalent to cleanroom-based methods regarding cellular integrity and sterility when appropriate quality of sterile filters is assured.