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1.

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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The periaqueductal grey (PAG) has been shown to be a major source of descending inhibition of dorsal horn cells (Textbook of Pain (1999) 309). However, few studies have demonstrated alterations in behavioural responses to noxious stimulation following inactivation of this nucleus. Many behavioural studies have looked for effects on nociceptive withdrawal thresholds in acute nociceptive tests. These tests would not reveal the presence of inhibition which is activated in response to noxious input. We have therefore investigated this possibility by studying behavioural responses to subcutaneous formalin injection in control animals, and in animals following partial sciatic nerve ligation (an animal model of neuropathic pain (Pain 43(2) (1990) 205). In control animals, microinjection of gamma-aminobutyric acid (GABA) to PAG did not significantly alter behavioural responses to formalin, while microinjection of D,L-homocysteic acid (DLH) reduced these responses. Responses to contralaterally applied formalin were significantly reduced in animals with partial sciatic ligation. Microinjection of GABA to PAG significantly increased these behavioural responses to formalin. We conclude that a component of PAG mediated inhibition of nociception is inactive under normal conditions. This inhibition may be activated by persistent nociceptive input, and possibly reflects long term changes in nociceptive circuitry which occur in neuropathic pain states.  相似文献   
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The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis. Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species.  相似文献   
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Summary MDL 72222 (1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate) is a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones. In the present study, the sucrose-gap technique has been used to record depolarizing responses to 5-HT from the cells of the rabbit nodose and superior cervical ganglia and to investigate the potency and selectivity of MDL 72222 as an antagonist of these responses.On nodose ganglia, responses to 5-HT were inhibited surmountably by MDL 72222 at concentrations up to 100 nmol/l. The threshold for antagonism was 2–10 nmol/l and the apparent pA2 value (Schild 1947) was 7.7±0.2,n=10. Blockade was selective since responses to GABA and noradrenaline were unaffected by MDL 72222, 100 nmol/l. With concentrations of MDL 7222 higher than 100 nmol/l, antagonism was concentration-related but not in a manner consistent with simple competitive antagonism and even a concentration of 1 mol/l failed to abolish the response to 5-HT.The results from the superior cervical ganglion were essentially similar to those obtained from the nodose ganglion. The threshold concentration of MDL 72222 for inhibition of 5-HT was 1–10 nmol/l and blockade was selective in that depolarizing responses to dimethylphenylpiperazinium (DMPP) was unaffected by a concentration of MDL 72222 of 1 mol/l.The data provide direct evidence that MDL 72222 is a potent and selective antagonist of the receptors for 5-HT which mediate depolarizing responses in vagal primary afferent cell bodies and in sympathetic ganglion cells.  相似文献   
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This study presents the relationships between ambient air pollutants and morbidity and emergency department visits among children and adults performed in Great Casablanca, the most populated and economic region in Morocco. This research was analyzed using conditional Poisson model for the period 2011–2013. In the period of study, the daily average concentrations of SO2, NO2, O3 and PM10 in Casablanca were 209.4 µg/m3, 61 µg/m3, 113.2 µg/m3 and 75.1 µg/m3, respectively. In children less than 5 years old, risk of asthma could be increased until 12% per 10 µg/m3 increase in NO2, PM10, SO2 and O3. In children over 5 years and adults, an increase of 10 µg/m3 air pollutant can cause an increase until 3% and 4% in respiratory consultations and acute respiratory infection, respectively. Similarly, impact on emergency department visits due to respiratory and cardiac illness was established. Our results suggest a not negligible impact on morbidity of outdoor air pollution by NO2, SO2, O3, and PM10.  相似文献   
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Journal of Immigrant and Minority Health - Much work has gone into unpacking the range of individual, interpersonal and structural barriers that prevent asylum-seekers from accessing healthcare. In...  相似文献   
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The aim of this paper is twofold. Firstly, to investigate the potential benefits of online health communities (OHCs) for informal caregivers by conducting a systematic literature review. Secondly, to identify the relationship between the potential benefits of OHCs and resilience factors of older adults. Performing a thematic analysis, we identified the potential benefits of OHCs for informal caregivers of older adults, including two salient themes: (a) caregivers sharing and receiving social support and (b) self and moral empowerment of caregivers. Then, we uncovered how these potential benefits can support resilience of older adults. Our findings show that sharing and receiving of social support by informal caregivers, and self and moral empowerment of informal caregivers in OHCs, can support four resilience factors among older adults, including self-care, independence, altruism and external connections. This review enables a better understanding of OHCs and Gerontology, and our outcomes also challenge the way healthcare and aged-care service providers view caregivers and older adults. Furthermore, the identified gap and opportunities would provide avenues for further research in OHCs.  相似文献   
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