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Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Methods

Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30?days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12?months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.

Results

Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.

Conclusions

No safety concerns arose, supporting the favorable benefit-risk profile of RZV.  相似文献   
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Although hepatitis E virus (HEV) is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries, locally acquired HEV infections are increasing in nonendemic countries. As such, HEV is emerging as an underdiagnosed cause of infection. This report describes three clinically variable cases of HEV infection with unusual clinical presentations. These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis (acute or chronic) with or without extrahepatic manifestations. HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions. Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection.  相似文献   
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Stress related to parenting a child with autism spectrum disorder can differently affect caregiver's physiological reactivity to acute stress. Here, parental stress levels, psychological characteristics, and coping strategies were assessed alongside measures of heart rate, heart rate variability, and cortisol during a psychosocial stress test in mothers of children with ASD (M‐ASD, n = 15) and mothers of typically developing children (n = 15). M‐ASD reported significantly higher levels of parental stress, anxiety, negative affectivity, social inhibition, and a larger preference for avoidance strategies. M‐ASD showed larger heart rate and cortisol responses to the psychosocial stress test. A positive relationship was found between parental stress levels and the magnitude of the cortisol stress response in both groups. The present findings indicate exaggerated physiological reactivity to acute psychosocial stress in M‐ASD and prompt further research to explore the role of individual differences in mediating the effects of parental stress on physiological stress responses.  相似文献   
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The 2008 dioxin crisis occurred as a result of contamination of Irish pork. The event had significant implications for Ireland’s economy and the reputation of its agricultural industry, as well as raising concerns for human health. This study describes the results of a content analysis of Irish and UK newspaper coverage of the 2008 Irish dioxin crisis, as this is likely to provide insight into how public perceptions of this issue were shaped. Articles from 16 print publications were systematically sampled for the period December 2008 to February 2009. The resulting data set of 141 articles was examined using a coding protocol developed based on previous research and refined during piloting. Results indicated that the dioxin crisis was primarily portrayed by the media as an industry/economic crisis, dominant in 26.9% of articles in the sample. Within this dominant portrayal, the agricultural industry was frequently cited as being in crisis (42.6%); however, the implications of the crisis on the wider economic environment also received attention (17.7%). Differences between Irish and UK-based media were also examined, revealing that while the Irish media most frequently described the crisis in terms of its impact on the industry and economy, the UK media were more likely to portray the crisis as a risk to health. These dominant media messages and message framings have implications for the public understanding of the issue in each country and potential consequences regarding perception of the adequacy of existing food policy and regulatory oversight.  相似文献   
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Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Patients and Methods

We conducted a multicenter retrospective analysis in the Triveneto region of Italy.

Results

One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.

Conclusion

This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.  相似文献   
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