Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Ph

Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (−18.5%; 95% confidence interval, −32.9 to −1.0; P = 0.04; and −8.2; 95% confidence interval, −16.3 to −0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials

International evaluation of the psychometrics of health-related quality of life questionnaires for use among long-term survivors of testicular and prostate cancer

Background: Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated in a comprehensive way whether a questionnaire used to evaluate HRQoL in cancer patients under active treatment is also reliable and valid when used among (long-term) cancer survivors. In this study we evaluated, in an international context, the psychometrics of HRQoL questionnaires for use among long-term, disease-free, survivors of testicular and prostate cancer. Methods: In this cross-sectional study, we recruited long-term survivors of testicular and prostate cancer from Northern and Southern Europe and from the United Kingdom who had participated in two phase III EORTC clinical trials. Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire, the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer) questionnaires, and the Impact of Cancer questionnaire. Testicular cancer survivors also completed subscales from the Nordic Questionnaire for Monitoring the Age Diverse Workforce. Results: Two hundred forty-two men (66% response rate) were recruited into the study. The average time since treatment was more than 10 years. Overall, there were few missing questionnaire data, although scales related to sexuality, satisfaction with care and relationship concern

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system

Temperature-dependent Wsm1 and Wsm2 gene-specific blockage of viral long-distance transport provides resistance to wheat streak mosaic virus and triticum mosaic virus in Wheat

Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) are economically important viral pathogens of wheat. Wheat cvs. Mace, carrying the Wsm1 gene, is resistant to WSMV and TriMV, and Snowmass, with Wsm2, is resistant to WSMV. Viral resistance in both cultivars is temperature sensitive and is effective at 18°C or below but not at higher temperatures. The underlying mechanisms of viral resistance of Wsm1 and Wsm2, nonallelic single dominant genes, are not known. In this study, we found that fluorescent protein–tagged WSMV and TriMV elicited foci that were approximately similar in number and size at 18 and 24°C, on inoculated leaves of resistant and susceptible wheat cultivars. These data suggest that resistant wheat cultivars at 18°C facilitated efficient cell-to-cell movement. Additionally, WSMV and TriMV efficiently replicated in inoculated leaves of resistant wheat cultivars at 18°C but failed to establish systemic infection, suggesting that Wsm1- and Wsm2-mediated resistance debilitated viral long-distance transport. Furthermore, we found that neither virus was able to enter the leaf sheaths of inoculated leaves or crowns of resistant wheat cultivars at 18°C but both were able to do so at 24°C. Thus, wheat cvs. Mace and Snowmass provide resistance at the long-distance movement stage by specifically blocking virus entry into the vasculature. Taken together, these data suggest that both Wsm1 and Wsm2 genes similarly confer virus resistance by temperature-dependent impairment of viral long-distance movement

Impact of timing and method of virus inoculation on the severity of wheat streak mosaic disease

Open Access Article; Published Online: 23 Jan 2018Wheat streak mosaic virus (WSMV), transmitted by the wheat curl mite Aceria tosichella, frequently causes significant yield loss in winter wheat throughout the Great Plains of the United States. A field study was conducted in the 2013–14 and 2014–15 growing seasons to compare the impact of timing of WSMV inoculation (early fall, late fall, or early spring) and method of inoculation (mite or mechanical) on susceptibility of winter wheat cultivars Mace (resistant) and Overland (susceptible). Relative chlorophyll content, WSMV incidence, and yield components were determined. The greatest WSMV infection occurred for Overland, with the early fall inoculations resulting in the highest WSMV infection rate (up to 97%) and the greatest yield reductions relative to the control (up to 94%). In contrast, inoculation of Mace resulted in low WSMV incidence (1 to 28.3%). The findings from this study indicate that both method of inoculation and wheat cultivar influenced severity of wheat streak mosaic; however, timing of inoculation also had a dramatic influence on disease. In addition, mite inoculation provided much more consistent infection rates and is considered a more realistic method of inoculation to measure disease impact on wheat cultivars

Newborn Hearing Screening And Early Diagnostic In The Nicu

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. 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(2008) Laryngoscope, 118 (7), pp. 1253-1256. , 2-s2.0-47149086791 10.1097/MLG.0b013e31816d726cOlusanya, B.O., Wirz, S.L., Luxon, L.M., Community-based infant hearing screening for early detection of permanent hearing loss in Lagos, Nigeria: A cross-sectional study (2008) Bulletin of the World Health Organization, 86 (12), pp. 956-963. , 2-s2.0-57149107570 10.2471/BLT.07.050005Holster, I.L., Hoeve, L.J., Wieringa, M.H., Willis-Lorrier, R.M.S., De Gier, H.H.W., Evaluation of hearing loss after failed neonatal hearing screening (2009) Journal of Pediatrics, 155 (5), pp. 646-650. , 2-s2.0-71749102175 10.1016/j.jpeds.2009.05.003Bielecki, I., Horbulewicz, A., Wolan, T., Risk factors associated with hearing loss in infants: An analysis of 5282 referred neonates (2011) International Journal of Pediatric Otorhinolaryngology, 75 (7), pp. 925-930. , 2-s2.0-79957855764 10.1016/j.ijporl.2011.04.007Hille, E.T., Van Straaten, H.L.M., Verkerk, P.H., Van Straaten, I., Verkerk, P., Hille, E., Baerts, W., Bos, A., Prevalence and independent risk factors for hearing loss in NICU infants (2007) Acta Paediatrica, International Journal of Paediatrics, 96 (8), pp. 1155-1158. , DOI 10.1111/j.1651-2227.2007.00398.