Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines.

UNLABELLED: Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNγ-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain. CONCLUSION: MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza.

Topical nasal steroids for treating nasal polyposis in people with cystic fibrosis.

BACKGROUND: Nasal polyps frequently occur in people with cystic fibrosis. Sinus infections have been shown to be a factor in the development of serious chest complications in these people. Nasal polyps have been linked to a higher risk of lower respiratory tract infections with Pseudomonas aeruginosa . Topical nasal steroids are of proven efficacy for treating nasal polyposis in the non-cystic fibrosis population. There is no clear current evidence for the efficacy of topical steroids for nasal polyps in people with cystic fibrosis. This is an updated version of a previously published review. OBJECTIVES: To assess the effectiveness of topical nasal steroids for treating symptomatic nasal polyps in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Latest search: 10 June 2015. SELECTION CRITERIA: Randomised and quasi-randomised controlled comparing the effects of topical nasal steroids to placebo in people with nasal polyps with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias in the included trial and extracted data. MAIN RESULTS: One single-centred trial (46 participants) was identified comparing a topical steroid (betamethasone) given as nasal drops to placebo. Treatment was given twice daily for six weeks; 22 participants received the active drug.Subjective symptom scores, change in polyp size, and side effects were assessed. There was no difference in nasal symptom scores between the treatment and placebo groups. Betamethasone was effective in reducing the size of polyps, but was associated with increased reports of mild side effects, nasal bleeding and discomfort.Risk of bias was high since over 50% of people enrolled did not complete the study. Follow-up of participants was short (six weeks) also reducing the significance of the results for clinical practice. AUTHORS' CONCLUSIONS: This review suggests topical steroids for nasal polyposis in people with cystic fibrosis have no demonstrable effect on subjective nasal symptom scores. They have some effect in reducing the size of the polyps, but due to the small sample size, poor completion rates and lack of follow-up, the trial is at high risk of bias and evidence for efficacy is limited. Overall there is no clear evidence for using topical steroids in people with cystic fibrosis and nasal polyposis.A well-designed randomised controlled trial of adequate power and long-term follow-up is needed. Validated measures of symptoms and physical findings should be performed and quality of life issues addressed.

Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic H1N1 infection.

UNLABELLED: 2009 H1N1 pandemic influenza (A(H1N1)pdm09) virus infected large numbers of people worldwide. Recent studies suggest infection with A(H1N1)pdm09 virus elicited cross-reactive anti-hemagglutinin (HA) memory B cell response to conserved regions of HA. However, the breadth and magnitude of cross-reactive immunity in children and adults following A(H1N1)pdm09 infection are unknown. METHODS: We investigated serum anti-HA immunity to a number of group-1 and -2 viruses in children and adults using hemagglutination inhibition (HAI), enzyme-linked immunosorbent assay and virus neutralization assay. RESULTS: Applying hemagglutination inhibition (HAI) titers ⩾40 against A(H1N1)pdm09 as threshold of sero-positivity, we observed significantly higher levels of anti-HA antibodies to a number of virus subtypes, including those neutralizing H5N1, in subjects with HAI titer ⩾40 than those with HAI <40. Adults demonstrated broader and stronger cross-reactive anti-HA antibodies than children, including cross-reactive anti-HA1 and -HA2 antibodies. By comparison, individuals with serologic evidence of recent exposure to seasonal H1N1 or H3N2 did not show such broad cross-reactive immunity. CONCLUSION: Our results suggest individuals exposed to A(H1N1)pdm09 virus developed a broad and age-associated cross-reactive anti-HA immunity which may have important implications for future vaccination strategies to enable protection against a broader range of influenza viruses.

Management of Bell's palsy in children: an audit of current practice, review of the literature and a proposed management algorithm.

OBJECTIVE: We carried out a complete audit cycle, reviewing our management of paediatric patients with Bell's palsy within 72 h of symptom onset. Our protocol was published after the initial audit in 2009, and a re-audit was carried out in 2011. We aimed to improve our current practice in accordance with up-to-date evidence-based research on the use of steroids and antivirals. PATIENTS AND METHODS: A total of 17 patients were included in the first cycle, but only eight patients met our inclusion and exclusion criteria for the re-audit. We assessed documentation of House-Brackmann (HB) grade on presentation, initial treatment, follow-up and recovery. RESULTS: The first cycle revealed inconsistent management with steroids (41%), antivirals (6%), steroids and antivirals (6%) or nothing at all (47%). In addition, only 65% of patients were followed-up in the ear, nose and throat (ENT) clinic. Our management protocol was published in 2010, and a re-audit was completed. Our results showed 100% compliance with steroid treatment and 100% follow-up with the ENT team. A thorough literature review revealed some additional benefit from the use of antivirals. CONCLUSIONS: At present there is insufficient evidence to discount the use of steroids and antivirals. Therefore, with our new management protocol, we recommend the use of steroids in patients presenting within 72 h of symptom onset, and antivirals for patients with a HB grade of IV or higher.

Does the HPV vaccination programme have implications for cervical screening programmes in the UK?

In the UK, a national HPV immunisation programme was implemented in 2008 for girls aged 12-13 years. In addition a catch-up programme was implemented for older girls up to 18 years of age from 2009 to 2011, with an uptake rate of 49.4%. Information about future uptake of cervical screening according to vaccination statistics is important in order to understand the impact of the vaccination programme and implications for a national cervical screening programme. We analysed data on a cohort of women who had been offered the HPV vaccine in the catch-up programme and were invited for cervical screening between 2010 and 2012 in Wales (n=30,882), in a record-linked database study, to describe the cervical screening uptake and clinical outcome according to HPV vaccination status. In our cohort, 48.5% (n=14,966) women had had HPV vaccination and 45.9% (n=14,164) women attended for cervical screening. Women who were unvaccinated were less likely to attend cervical screening (adjusted OR 0.58; 95% CI (0.55, 0.61)). Of those who attended for screening, 13.9% of vaccinated women had abnormal cytology reported compared to 16.7% of women who were unvaccinated. Women who lived in areas with high levels of social deprivation were less likely to be vaccinated (Quintile 5 OR 0.48 95% CI (0.45, 0.52)) or attend cervical screening (Quintile 5 OR 0.70; 95% CI (0.65, 0.75)) compared to those who lived in the least deprived areas. These data highlight the need for new strategies to address inequalities in cervical screening uptake and can inform further mathematical modelling work to clarify the impact of the HPV vaccination programme on future cervical cancer incidence.

UK population based study to predict impact of HPV vaccination.

BACKGROUND: In 2008 a human papillomavirus (HPV) vaccination programme for cervical cancer prevention was implemented in the UK. Surveillance of vaccine uptake, impact on prevalence of HPV infection and cervical cancer incidence were identified as key measures to evaluate the intervention. OBJECTIVE: To determine baseline HPV prevalence in unvaccinated women and predict impact of HPV vaccination on high-grade cervical disease (CIN2+). STUDY DESIGN: A pseudo-anonymous prospective cohort was sampled on entry to the routine cervical screening programme between March 2009 and November 2010. In total, 13,306 eligible females were identified and high-risk (hrHPV) type specific status determined. Potential impact of prophylactic vaccination on CIN2+ was calculated by applying HPV vaccine clinical trial data to the baseline HPV type-specific data. RESULTS: Of 13,306 samples tested, 3545 (26.6%) were confirmed positive for at least one hrHPV type and 1325 (10%) were positive for low risk HPV. HPV16 was the predominant type detected in cases positive with either single or multiple hrHPV infection(s) (5.2% and 4.7%, respectively). Based on hrHPV type-specific data, Gardasil would have prevented 33.2% HPV16/18 unrelated CIN2+ compared to 47.1% for Cervarix. This difference was not statistically significant. CONCLUSION: Prior to the introduction of the HPV vaccine, approximately one-quarter of young women were positive for hrHPV and one-tenth positive for HPV16. Post-vaccination, we anticipate a substantial absolute risk reduction in high-grade cervical disease associated with both targeted and non-targeted hrHPV types. There is no significant difference between the two commercially available vaccines in terms of clinical impact.

Topical nasal steroids for treating nasal polyposis in people with cystic fibrosis.

BACKGROUND: Nasal polyps frequently occur in people with cystic fibrosis. Sinus infections have been shown to be a factor in the development of serious chest complications in these people. Nasal polyps have been linked to a higher risk of lower respiratory tract infections with Pseudomonas aeruginosa . Topical nasal steroids are of proven efficacy for treating nasal polyposis in the non-cystic fibrosis population. There is no clear current evidence for the efficacy of topical steroids for nasal polyps in people with cystic fibrosis. OBJECTIVES: To assess the effectiveness of topical nasal steroids for treating symptomatic nasal polyps in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Latest search: 25 January 2013. SELECTION CRITERIA: Randomised and quasi-randomised controlled comparing the effects of topical nasal steroids to placebo in people with nasal polyps with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias in the included trial and extracted data. MAIN RESULTS: One single-centred trial (46 participants) was identified comparing a topical steroid (betamethasone) to placebo. Twenty-two participants received the active drug.Subjective symptom scores, change in polyp size, and side effects were assessed. There was no difference in nasal symptom scores between the treatment and placebo groups. Betamethasone was effective in reducing the size of polyps, but was associated with increased reports of mild side effects, nasal bleeding and discomfort.Risk of bias was high since over 50% of people enrolled did not complete the study. Follow-up of patients was short (six weeks) also reducing the significance of the results for clinical practice. AUTHORS' CONCLUSIONS: This review suggests topical steroids for nasal polyposis in patients with cystic fibrosis have no demonstrable effect on subjective nasal symptom scores. They have some effect in reducing the size of the polyps, but due to the small sample size, poor study completion rates and lack of follow-up, the study is at high risk of bias and evidence for efficacy is limited. Overall there is no clear evidence for using topical steroids in people with cystic fibrosis and nasal polyposis.A well-designed randomised controlled trial of adequate power and long-term follow-up is needed. Validated measures of symptoms and physical findings should be performed and quality of life issues addressed.

Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses.

Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. An enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nose-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B cell responses to pH1N1, seasonal H1N1 (sH1N1), and avian H5N1 (aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1, and aH5N1 viruses. The 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity to not only H1N1 but also aH5N1 viruses. These findings may have important implications for future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells.

Impact of media reporting of cervical cancer in a UK celebrity on a population-based cervical screening programme.

OBJECTIVES: To determine the impact of media reporting of cervical cancer in a UK celebrity on cervical screening uptake, response time and colposcopy referral and attendance. SETTING: Population-based national cervical screening programme for women in Wales, UK. METHODS: A time series regression analysis of the Welsh national cervical screening and colposcopy databases was used to examine the number of smear tests carried out between 2000 and 2010, stratified by age group and deprivation indicators. Logistic regression was used to analyse colposcopy attendance. RESULTS: Over 33,000 more cervical screening tests than expected were carried out in the year of media reporting (2008/9), 11,539 (35%) of which were in the month of Jade Goody's death. The largest increase was evident in women aged 35-39 years (475 additional tests per month, 95% CI 331-619). Impacts were similar across deprivation quintiles. Colposcopy referrals increased by 18% during the year of media reporting. Increases were observed for all smear test results in 2008/9, particularly among younger women, and further rises were evident in 2009/10 for smear tests showing borderline changes and mild dyskaryosis. The proportion of women attending colposcopy appointments rose in the year of media reporting (χ(2) = 45.8, P < 0.001). CONCLUSIONS: Mass media reporting of cervical cancer in a UK celebrity was associated with a significant, but transient, increase in screening uptake and colposcopy referral and attendance. Mass media reporting can play a role in enhanced detection of abnormalities, but public health messages must be communicated effectively to minimize anxiety whilst maximizing case-finding and uptake among non-responders.

Single negative colposcopy: is it enough to rule out high-grade disease?

It has been proposed that women who have a negative colposcopic examination or who have no cervical intraepithelial neoplasia (CIN) on colposcopic biopsy can be safely returned to routine screening with the next visit being three or five years later. We present data regarding 551 women who had colposcopy in Wales for a low-grade cytological abnormality and who were followed through Cervical Screening Wales for subsequent CIN. Of 436 women declared CIN free initially, 26 (6.0%) had high-grade CIN diagnosed on follow-up. We suggest that additional screening at an interval of less than three years should be offered to women with a negative colposcopy or a biopsy without CIN.

Topical nasal steroids for treating nasal polyposis in people with cystic fibrosis.

BACKGROUND: Nasal polyps frequently occur in people with cystic fibrosis. Sinus infections have been shown to be a factor in the development of serious chest complications in these people. Nasal polyps have been linked to a higher risk of lower respiratory tract infections with Pseudomonas aeruginosa . Topical nasal steroids are of proven efficacy for treating nasal polyposis in the non-cystic fibrosis population. There is no clear current evidence for the efficacy of topical steroids for nasal polyps in people with cystic fibrosis. OBJECTIVES: To assess the effectiveness of topical nasal steroids for treating symptomatic nasal polyps in people with cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Latest search: 02 February 2011. SELECTION CRITERIA: Randomised and quasi-randomised controlled comparing the effects of topical nasal steroids to placebo in people with nasal polyps with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias in the included trial and extracted data. MAIN RESULTS: One single-centred trial (46 participants) was identified comparing a topical steroid (betamethasone) to placebo. Twenty-two participants received the active drug.Subjective symptom scores, change in polyp size, and side effects were assessed. There was no difference in nasal symptom scores between the treatment and placebo groups. Betamethasone was effective in reducing the size of polyps, but was associated with increased reports of mild side effects, nasal bleeding and discomfort.Risk of bias was high since over 50% of people enrolled did not complete the study. Follow-up of patients was short (six weeks) also reducing the significance of the results for clinical practice. AUTHORS' CONCLUSIONS: This review suggests topical steroids for nasal polyposis in patients with cystic fibrosis have no demonstrable effect on subjective nasal symptom scores. They have some effect in reducing the size of the polyps, but due to the small sample size, poor study completion rates and lack of follow-up, the study is at high risk of bias and evidence for efficacy is limited. Overall there is no clear evidence for using topical steroids in people with cystic fibrosis and nasal polyposis.A well-designed randomised controlled trial of adequate power and long-term follow-up is needed. Validated measures of symptoms and physical findings should be performed and quality of life issues addressed.

Challenging airways in deep neck space infections.

Skilful airway management is critical in deep neck space infections. Although relatively uncommon, this spectrum of disease presents a clinical challenge for otolaryngologists and anesthetists. There is currently no universal agreement on the ideal method of airway control for these patients because this depends on various factors including available local expertise and equipment. We review the literature and discuss the available options of airway management in these head and neck emergencies. Special consideration is given to awake fiberoptic intubation and tracheotomy under local anesthesia. Relevant anatomy, route of spread and microbiology of deep neck space infections are also briefly discussed.

Reviewing interval cancers: time well spent?

OBJECTIVES: To categorize interval cancers, and thus identify false-negatives, following prevalent and incident screens in the Welsh breast screening programme. SETTING: Breast Test Wales (BTW) Llandudno, Cardiff and Swansea breast screening units. METHODS: Five hundred and sixty interval breast cancers identified following negative mammographic screening between 1989 and 1997 were reviewed by eight screening radiologists. The blind review was achieved by mixing the screening films of women who subsequently developed an interval cancer with screen negative films of women who did not develop cancer, in a ratio of 4 to 1. Another radiologist used patients' symptomatic films to record a reference against which the reviewers' reports of the screening films were compared. Interval cancers were categorized as 'true', 'occult', 'false-negative' or 'unclassified' interval cancers or interval cancers with minimal signs, based on the National Health Service breast screening programme (NHSBSP) guidelines. RESULTS: Of the classifiable interval films, 32% were false-negatives, 55% were true intervals and 12% occult. The proportion of false-negatives following incident screens was half that following prevalent screens (P = 0.004). Forty percent of the seed films were recalled by the panel. CONCLUSIONS: Low false-negative interval cancer rates following incident screens (18%) versus prevalent screens (36%) suggest that lower cancer detection rates at incident screens may have resulted from fewer cancers than expected being present, rather than from a failure to detect tumours. The panel method for categorizing interval cancers has significant flaws as the results vary markedly with different protocol and is no more accurate than other, quicker and more timely methods.