Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A

A replication-deficient chimpanzee adenovirus expressing Ag85A (ChAdOx1.85A) was assessed, both alone and in combination with modified vaccinia Ankara also expressing Ag85A (MVA85A), for its immunogenicity and protective efficacy against a Mycobacterium tuberculosis (M.tb) challenge in mice. Naïve and BCG-primed mice were vaccinated or boosted with ChAdOx1.85A and MVA85A in different combinations. Although intranasally administered ChAdOx1.85A induced strong immune responses in the lungs, it failed to consistently protect against aerosol M.tb challenge. In contrast, ChAdOx1.85A followed by MVA85A administered either mucosally or systemically, induced strong immune responses and was able to improve the protective efficacy of BCG. This vaccination regime has consistently shown superior protection over BCG alone and should be evaluated further.     

Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation

Background

Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction.

Topical tranexamic acid for the treatment of acute epistaxis in the emergency department

Objective

To evaluate the effectiveness and potential benefits of topical tranexamic acid (TXA) in the management of acute epistaxis.

Intranasal delivery of rapid-onset antidepressants: a new trend of treating major depressive disorder

Existing antidepressants seem to have an onset time of several weeks. However, newly found depression-related receptors and pathways may enlighten us to find more rapid-onset antidepressants, in which ketamine is one of the most potential antidepressants. By intranasal administration, drugs can be directly delivered to the brain via olfactory nerve route, which is proved to be suitable for some antidepressants. Well-designed rapid-onset antidepressants are the urgent requirements of the patients with depression. Intranasal administration, as a potential strategy to deliver antidepressants to brain, can improve drug efficacy and largely shorten the onset time. In this article, we sorted out some new formulation approaches in treating depression with different mechanisms and pathways compared with traditional treating strategies, along with new findings in clinical studies, proving that the combination of rapid-onset antidepressants with intranasal delivery will lead a new trend in treating depression.     

Case series of undetected intranasal impression material in patients with clefts

We report the cases of two female patients in their twenties who had had corrective surgery for bilateral cleft lip and palate as babies. They had both had residual palatal fistulas and had had further treatment that required repeated dental impressions. Several years later both had complained of persistent nasal discomfort and discharge, and routine clinical examination and investigations had failed to identify the cause. Full examination of the whole nasal cavity under general anaesthesia, in both cases, showed the presence of displaced dental impression material in the nasal floor. Removal resulted in complete resolution of symptoms.     

右美托咪定术前滴鼻对全麻患儿术后行为改变的影响

目的观察右美托咪定术前滴鼻对全麻患儿术后行为改变的影响。方法择期在全麻下行疝囊高位结扎术的患儿60例,男46例,女14例,年龄2~5岁,体重10~30kg,ASAⅠ或Ⅱ级。采用随机数字表法,将其均分为三组:对照组(C组)、咪达唑仑组(M组)和右美托咪定组(D组)。麻醉诱导前30min,C组生理盐水0.02ml/kg滴鼻,M组咪达唑仑0.2mg/kg滴鼻,D组右美托咪定2μg/kg滴鼻。记录患儿与父母分离时的镇静评分及七氟醚诱导时的面罩接受程度评分;记录患儿术后恢复时间、术后并发症及镇痛药补救率等情况。分别在术前1d、术后1、7、30d用术后行为量表(PHBQ)对患儿父母进行术前问卷调查及术后电话随访,观察患儿术后行为改变的情况。结果M组和D组与父母分离时的镇静评分及七氟醚诱导时的面罩接受程度评分明显高于C组(P0.05)。D组苏醒期躁动、恶心呕吐及镇痛药补救率明显低于C组和M组(P0.05)。术后1、7d时M组和D组行为改变的发生率明显低于C组(P0.05)。结论右美托咪定术前滴鼻可以降低全麻患儿术后行为改变的发生率。     

Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop proceedings,National Institute of Allergy and Infectious Diseases,Bethesda, Maryland,USA, May 21, 2015

On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities. Meeting participants presented the results and experience of representative clinical trials of NA vaccines using a variety of alternative delivery devices, as well as a broader group of methods studied in animal models and at bench top, to improve upon the performance and/or avoid the drawbacks of conventional needle-syringe (N–S) delivery. The subjects described and discussed included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and lower respiratory, and intramuscular tissues; (2) devices and techniques for jet injection, solid, hollow, and dissolving microneedles, patches for topical passive diffusion or iontophoresis, electroporation, thermal microporation, nasal sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA, synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and microparticle vectors; and (4) the clinical experience and humoral, cellular, and cytokine immune responses observed for many of these target tissues, technologies, constructs, and carriers. This report summarizes the presentations and discussions from the workshop (https://web.archive.org/web/20160228112310/https://www.blsmeetings.net/NucleicAcidDeliveryDevices/), which was webcast live in its entirety and archived online (http://videocast.nih.gov/summary.asp?live=16059).     

Toxicity evaluation and nasal mucosal tissue deposition of dexamethasone-infused mucoadhesive in situ nasal gelling systems

To demonstrate safety of a developed intranasal dexamethasone-infused in situ gelling formulation, quantification of a validated clinical biomarker indicative of cytotoxic potential using a human sinonasal explant model was first confirmed. Systematic cytotoxicity studies using the lactate dehydrogenase (LDH) detection assay revealed no elevation from baseline, in LDH levels, with tissue integrity of explanted human nasal mucosa also maintained; this was further corroborated using tissue histopathological examination. Next, with safety confirmed ex vivo, freshly excised human nasal tissue was utilised to quantify dexamethasone release from the lead sol–gel systems; this being achieved through development and validation of a HPLC-UV analytical method, which reliably quantified controlled therapeutic release and deposition into mucosal tissue. Collectively, these findings indicate promise in the safety of each excipient within the concentrations employed in the functional sol–gel system, complemented by successful and reliable drug release and deposition into human nasal mucosal tissue. These findings pave the way for application of the dexamethasone-based sol–gel system to the extended delivery of corticosteroids to nasal mucosa in the management of localised inflammatory conditions of an acute and chronic nature, such as chronic rhinosinusitis, which can be expected to benefit from controlled and extended drug delivery characteristics imparted by appropriately engineered in situ gelling systems.     

The effect of medical treatment on nasal exhaled nitric oxide (NO) in patients with persistent allergic rhinitis: A randomized control study

PurposeThis study aimed to evaluate the role of nasal nitric oxide (NO) in the management of patients with persistent allergic rhinitis (PER).MethodsIt was a randomized and comparative study. The study subjects were classified as controls (healthy subjects) or patients with PER based on defined criteria. All clinical, functional and biological data were collected for analyzing. Nasal fractional exhaled nitric oxide (FENO) was measured by electroluminescence device. Patients with PER were randomized for treatment with antihistamine (ATH) combined with leukotriene receptor antagonists (LRA) or only with intranasal steroids (INS).ResultsDuring two years, 501 subjects were included: 234 control subjects and 267 patients with PER. The levels of nasal NO, total IgE, blood eosinophil counts, and apnea-hypopnea index (AHI) in patients with PER were higher than controls (P < 0.001; P < 0.05; P < 0.05; P < 0.01; respectively). There were statistically significant correlations between nasal NO, nasal peak flows, total IgE, and blood eosinophil counts in patients with PER (R = −0.687 and P = 0.0012; R = −0.643 and P = 0.0018; R = 0.432 and P = 0.0024; R = 0.445 and P = 0.002; respectively). After 6 months of treatment, patients treated with INS had greater improvement of clinical symptoms and reduction of nasal NO values than patients treated with ATH + LRA (985 ± 253 vs. 732 ± 298 ppb; P < 0.05).ConclusionNasal NO measurement is a useful tool for the follow-up of patients with PER. It also helps clinicians to estimate the level of response to treatment in patients with PER.