Vaccination, information and parental confidence in the digital age in England.

Background: Immunisation programmes have led to substantial reductions in vaccine-preventable infectious diseases globally. A variety of factors have been shown to impact parental confidence and uptake of childhood vaccines, from concerns about vaccine safety to a lack of perceived need. Determinants of vaccine decision making include information, risk perceptions, and modifying factors such as attitude, identity, norms, habit and barriers. With the rise of the internet and social media, there has been a vast increase in information available about vaccines, not all scientifically-based and well-informed. Methods: 285 locations in England were randomly selected to survey a nationally representative sample of the English population. 1735 primary care givers of children aged between 2 months and <5 years old from England were randomly selected and surveyed via face-to-face interviews between January and March 2019. Results: A much higher percentage of parents surveyed trust health care workers, the NHS, pharmacists and government for advice about immunisation, in comparison to media, the internet and social media. Most parents use official sources to obtain information on vaccines including parents who use the internet. The small proportion of parents who reported having seen negative information about vaccines were more likely to find it on the internet. Parents who felt they did not have enough information were more likely to have delayed or refused a vaccine for their child. Interpretation: This study showed that for parents of young children in England, vaccination continues to be the social norm but this can rapidly change and clear, consistent messaging from trusted sources continues to be important. Although a proportion do seek vaccine information on the internet, the majority use official sources. Representative attitudinal surveys continue to be key in identifying any emerging threats to parental vaccine confidence.

'My primary purpose is to protect the unborn child': Understanding pregnant women's perceptions of maternal vaccination and vaccine trials in Europe.

Despite the important benefits of maternal vaccination for pregnant women and newborns, vaccination uptake is low in many European countries. Differences in vaccination policies and recommendations, as well as concerns about vaccine safety can partly explain inadequate coverage rates and women's hesitancy to get vaccinated during pregnancy. This study aims to explore pregnant women's experiences, decision-making processes and perceptions towards maternal vaccination and maternal vaccine trials in France, Germany, Italy, Spain and the United Kingdom. Qualitative interviews and focus groups were conducted with 258 pregnant women identified through local research panels and snowballing. Topic guides translated in local languages were designed to explore women's awareness and perceptions of maternal vaccination, and willingness to participate in vaccine trials during pregnancy. A thematic analysis was conducted. Pregnant women were found to have low awareness about maternal vaccination, with many reporting not having received a recommendation to vaccinate from their doctors. Strong trust in health professionals indicate that strengthened recommendations could improve vaccination uptake. Vaccination decision-making in pregnancy was described in the context of a highly emotional period, generating anxiety and fears around the safety of vaccines. Pregnancy was also discussed as a period during which women develop nurturing and protective identities. However, depending on the information they received as well as influences from experts, families and peers, women either perceived vaccination as a threat to their babies' safety or as a means to protect them. Attitudes towards maternal vaccine trials were less ambiguous, with most pregnant women strongly rejecting the notion of taking part in trials. While strategies to improve pregnant women's awareness and perceptions of maternal vaccination are needed, it is equally important to understand why healthcare professionals may not be recommending vaccination. More coordinated strategies across Europe could help strengthen communication and trust in maternal vaccination.

Trust, emotions and risks: Pregnant women's perceptions, confidence and decision-making practices around maternal vaccination in France.

Maternal vaccination is an important strategy to reduce maternal and newborn mortality and morbidity. Yet, vaccination uptake is suboptimal in many countries, including France. This mixed-method study aimed to identify factors influencing maternal vaccination, exploring pregnant women's perceptions, confidence, and decision-making processes in France. Maternal vaccination uptake was positively associated with awareness of maternal vaccines, confidence in vaccine effectiveness and receiving a recommendation from a healthcare professional. A trusting relationship with healthcare professionals was observed as crucial for women during pregnancy. Even if women considered themselves as sole decision-makers, healthcare professionals' role in decision-making was viewed as substantial. Pregnancy can be a complex time for assessing risks, which was evident in the strong emotional reactions to maternal vaccination and anxieties about safety. As new maternal vaccines are developed, it is crucial to consider women's values, risk perceptions and emotions in the development of strategies to support acceptance of maternal vaccination.

Strengthening HPV vaccination delivery: findings from a qualitative service evaluation of the adolescent girls' HPV vaccination programme in England.

BACKGROUND: In 2014, the number of HPV vaccine doses given to adolescent girls as part of the English school-based immunization programme was reduced from three to two. This was based on evidence that a two-dose schedule provides long-lasting protection against HPV infection. In 2015/16 a small decline in HPV vaccination coverage in adolescent girls was noted; from 86.7% for the three-dose schedule in 2013/14 to 85.1% for the two-dose schedule. This evaluation examined whether service-related factors contributed to this decline. METHODS: In May-August 2017, we conducted semi-structured qualitative interviews with 39 participants responsible for commissioning or delivering immunization programmes in six local authorities in the South West, North Central Midlands and South Central Midlands, England. RESULTS: Effective planning and data management were key for successful service provision of HPV vaccination, as well as close collaboration between commissioners, service providers and data system managers, a team skill mix with experienced staff, pro-active engagement with schools and service providers equipped to respond to parental concerns. CONCLUSIONS: To maintain and improve the high HPV adolescent girls' vaccine coverage rates achieved in England, in the context of an expanding school-based immunization programme, it is essential to strengthen the organizational capacity of the delivery system.

Sample preparation with sucrose cryoprotection dramatically alters Zn distribution in the rodent hippocampus, as revealed by elemental mapping.

Transition metal ions (Fe, Mn, Cu, Zn) are essential for healthy brain function, but altered concentration, distribution, or chemical form of the metal ions has been implicated in numerous brain pathologies. Currently, it is not possible to image the cellular or sub-cellular distribution of metal ions in vivo and therefore, studying brain-metal homeostasis largely relies on ex vivo in situ elemental mapping. Sample preparation methods that accurately preserve the in vivo elemental distribution are essential if one wishes to translate the knowledge of elemental distributions measured ex vivo toward increased understanding of chemical and physiological pathways of brain disease. The choice of sample preparation is particularly important for metal ions that exist in a labile or mobile form, for which the in vivo distribution could be easily distorted by inappropriate sample preparation. One of the most widely studied brain structures, the hippocampus, contains a large pool of labile and mobile Zn. Herein, we describe how sucrose cryoprotection, the gold standard method of preparing tissues for immuno-histochemistry or immuno-fluorescence, which is also often used as a sample preparation method for elemental mapping studies, drastically alters hippocampal Zn distribution. Based on the results of this study, in combination with a comparison against the strong body of published literature that has used either rapid plunge freezing of brain tissue, or sucrose cryo-protection, we strongly urge investigators in the future to cease using sucrose cryoprotection as a method of sample preparation for elemental mapping, especially if Zn is an analyte of interest.

Strategies to improve maternal vaccination acceptance.

BACKGROUND: In England, influenza and pertussis vaccination has been recommended for all pregnant women since 2010 and 2012 respectively. However, in some areas, vaccination uptake rates have been low. A qualitative study was conducted to gain a contextualised understanding of factors influencing vaccination acceptance during pregnancy in Hackney, a borough in north-east London, UK. This paper draws on in-depth insights gained from the above study, to provide recommendations for increasing long-term maternal vaccination acceptance. METHODS: Hackney was chosen as the study site because it has one of the lowest vaccination coverage rates in pregnancy in the UK. A maximum variation sampling method was used to recruit 47 pregnant and recently pregnant women from a wide range of backgrounds, as well as ten healthcare professionals from three general practices; two community antenatal clinics; nine parent-toddler groups; and four community centres. In-depth interviews and a video-recording of a pregnant patient's consultation, explored experiences of care within the National Health Service during pregnancy, and women's views about maternal vaccination. In-depth interviews with healthcare professionals explored their views towards, and how they discuss and provide maternal vaccination. Study data were analysed both deductively, through drawing on insights from anthropological works that address diverse conceptualisations and practices around vaccination; and inductively, with a thematic analysis approach. RESULTS: The findings of this study and the recommendations based on them were divided into five broad themes: access to maternal vaccination; healthcare institution rhetoric and its effect on maternal vaccination acceptance; community and family influences on maternal vaccination decisions; healthcare professionals' views towards maternal vaccination; and the influence of patient-healthcare professional relationships on maternal vaccination acceptance. CONCLUSIONS: The strategies to improve maternal vaccination acceptance recommended in this paper would engender a more open and democratised healthcare system.

Elemental characterisation of the pyramidal neuron layer within the rat and mouse hippocampus.

A unique combination of sensitivity, resolution, and penetration make X-ray fluorescence imaging (XFI) ideally suited to investigate trace elemental distributions in the biological context. XFI has gained widespread use as an analytical technique in the biological sciences, and in particular enables exciting new avenues of research in the field of neuroscience. In this study, elemental mapping by XFI was applied to characterise the elemental content within neuronal cell layers of hippocampal sub-regions of mice and rats. Although classical histochemical methods for metal detection exist, such approaches are typically limited to qualitative analysis. Specifically, histochemical methods are not uniformly sensitive to all chemical forms of a metal, often displaying variable sensitivity to specific "pools" or chemical forms of a metal. In addition, histochemical methods require fixation and extensive chemical treatment of samples, creating the strong likelihood for metal redistribution, leaching, or contamination. Direct quantitative elemental mapping of total elemental pools, in situ within ex vivo tissue sections, without the need for chemical fixation or addition of staining reagents is not possible with traditional histochemical methods; however, such a capability, which is provided by XFI, can offer an enormous analytical advantage. The results we report herein demonstrate the analytical advantage of XFI elemental mapping for direct, label-free metal quantification, in situ within ex vivo brain tissue sections. Specifically, we definitively characterise for the first time, the abundance of Fe within the pyramidal cell layers of the hippocampus. Localisation of Fe to this cell layer is not reproducibly achieved with classical Perls histochemical Fe stains. The ability of XFI to directly quantify neuronal elemental (P, S, Cl, K, Ca, Fe, Cu, Zn) distributions, revealed unique profiles of Fe and Zn within anatomical sub-regions of the hippocampus i.e., cornu ammonis 1, 2 or 3 (CA1, CA2 or CA3) sub-regions. Interestingly, our study reveals a unique Fe gradient across neuron populations within the non-degenerating and pathology free rat hippocampus, which curiously mirrors the pattern of region-specific vulnerability of the hippocampus that has previously been established to occur in various neurodegenerative diseases.

Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

A case report of Lemierre's Syndrome associated with dental sepsis.

INTRODUCTION: Lemierre's syndrome is a potentially fatal condition characterised by spread of an oropharyngeal infection, resulting in thrombosis of the internal jugular vein. This leads to septicaemia and possible metastatic abscesses. CASE PRESENTATION: We discuss the case of a previously healthy 17-year-old male who developed Lemierre's syndrome following dental sepsis. He presented with bilateral submandibular and submental swelling extending into the neck and chest. His management included a tracheostomy; incision and drainage of the abscesses; drainage of a pleural effusion and prolonged anticoagulant therapy. CONCLUSION: The incidence of Lemierre's disease appears to be increasing and early diagnosis is essential. A high index of suspicion is needed in cases of oropharyngeal infection followed by fever, tender swelling of the neck and dysphagia - especially in young patients.

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.

Caloric restriction provided after global ischemia does not reduce hippocampal cornu ammonis injury or improve functional recovery.

Since caloric restriction (CR) can modify multiple pathways central to the ischemic cascade and enhance neuroplasticity mechanisms, we hypothesized that CR should exert protective effects following brain ischemia. Previous studies have suggested benefit when CR was administered prior to ischemia. We investigated whether prolonged CR beginning after global ischemia would result in lasting protection as assessed by performance in the open field, as a measure of functional outcome, and hippocampal CA1 neuronal counts. Adult, male Mongolian gerbils were subjected to 5 min bilateral carotid artery occlusion (ISCH) or sham surgery (SHAM) with tympanic temperature maintained at 36.5+/-0.2 degrees C during the intra-ischemic period. After screening out gerbils with incomplete ischemia, each of the two surgical groups were randomly assigned to control diet (CON) or 30% CR for the duration of the study (60 d). Gerbils were tested in the open field on d3, 7, 10, 30 and 60. ISCH-CON animals showed a significantly higher level of activity in the open field (impaired habituation) compared to SHAM-CON gerbils on all test days (P<0.001). Open field activity was significantly lower in the ISCH-CR group than in ISCH-CON gerbils only on d7 (P=0.024). Open field activity of the SHAM-CR gerbils showed a trend to increase relative to that of SHAM-CON gerbils during the last 30 d of the study (P=0.055 on d60), raising the question of suitability of the open field test for long-term studies of CR and ischemia. Brain sections obtained at d60 were stained with hematoxylin and eosin. Hippocampal CA1 neuron counts were significantly reduced by ischemia (P<0.001), and there was no sparing effect of CR. Our findings suggest that prolonged 30% CR administered beginning after global ischemia cannot diminish brain injury or enhance long-term recovery.

Maintaining standards of aesthetic practice in trainees subject to NHS restrictions.

The Specialist Advisory Committee (SAC) in plastic surgery within the United Kingdom (UK) recommends a modular training programme to include aesthetic surgery. The intercollegiate board examinations test candidates on all aspects of aesthetic practice yet there is no formal, national aesthetic training in the UK. Closure of National Health Service (NHS) private patient facilities has reduced training opportunity [Nicolle FV. Sir Harold Gillies Memorial Lecture; Aesthetic plastic surgery and the future plastic surgeon. Br J Plast Surg 1998;51:419-24.] Calmanisation [Hospital doctors: training for the future. The Report of the Working Group on Specialist Medical Training (The Calman Report). London: HMSO; 1993.], the European Working Time Directive (EWTD) [; Phillips H, Fleet Z, Bowman K. The European Working time Directive-interim report and guidance from The Royal College of Surgeons of England working party chaired by Mr Hugh Phillips; 2003 []; Chesser S, Bowman K, Phillips H. The European Working Time Directive and the training of surgeons. BMJ Careers Focus 2002;s69-7.], and more importantly the implementation of "local" aesthetic guidelines have placed further pressures on training. Reductions of NHS case mix will ultimately lead to a reduction in trainee experience. With increasing regulatory pressure from the Commission for Healthcare Improvement, standards of aesthetic practice can only be maintained by increasing private/independent sector involvement. At present a disparity exists between the demand and provision of aesthetic surgery training in the UK. Aesthetic surgery forms part of the training curriculum for plastic surgery and as such remains a training issue. A review of aesthetic surgery training is needed in the UK through consultation with trainers and trainee representatives.

Mesh assisted direct closure of bilateral TRAM flap donor sites.

The pedicled transverse rectus abdominis myocutaneous (TRAM) flap remains a popular choice for patients requesting breast reconstruction. Criticism of all techniques that harvest the rectus abdominis muscle centre on abdominal wall weakness.[Dulin WA, Avila RA, Verheyden CN, Grossman L. Evaluation of abdominal wall strength after TRAM flap surgery. Plast Reconstr Surg 2004; 113: 1662-1665] Primary fascial closure of the donor site has been shown to reduce abdominal wall weakness and the subsequent risk of hernia and bulge. [Mizgala CL, Hartrampf CR Jr, Bennett GK. Abdominal function after pedicled TRAM flap surgery. Clin Plast Surg 1994; 21: 255-272]2 Primary fascial closure of all uni-lateral and most bilateral muscle preserving TRAM flap donor sites is possible. In a series of 23 bilateral TRAM flaps, excessive abdominal tension prevented direct fascial closure of the donor site in seven. Using a technique that includes muscle preservation, muscle relaxation and mesh assistance; tensionfree, direct fascial closure was achieved in all. The mesh buttress supports the rectus sheath during closure and provides long term shape and stability.

Validation and clinical application of molecular methods for the identification of molds in tissue.

BACKGROUND: Invasive fungal infections due to less-common molds are an increasing problem, and accurate diagnosis is difficult. METHODS: We used our previously established molecular method, which allows species identification of molds in histological tissue sections, to test sequential specimens from 56 patients with invasive fungal infections who were treated at our institution from 1982 to 2000. RESULTS: The validity of the method was demonstrated with the establishment of a molecular diagnosis in 52 cases (93%). Confirmation of the causative organism was made in all cases in which a mold had been cultured from the tissue specimen. Less-common molds were identified in 7% of cases and appear to be an increasing problem. CONCLUSIONS: Our previously established method has proven to be of value in determining the incidence of invasive infection caused by less-common molds. Institutions should continue to pursue diagnosis of invasive fungal infections by means of tissue culture and microbiologic analysis.

Alveolar bone grafting: achieving the organisational standards determined by CSAG, a baseline audit at the Birmingham Children's Hospital.

INTRODUCTION: Birmingham Children's Hospital (BCH) is the centre for a regional comprehensive cleft service attempting to implement the national guidelines for minimum standards of care. A national audit of cleft management (CSAG) found that 58% of alveolar bone grafts were successful; published series suggest that success rates can be of the order of 95%. We present the results of an audit of alveolar bone grafting over a 33-month period, after implementation. PATIENTS AND METHODS: A retrospective clinical process audit was taken from the hospital notes and an analysis of radiological outcome by Bergland score was obtained by two independent assessors. RESULTS: The audit highlighted the difficulties of integrating the increased clinical workload. Other difficulties included poorly standardised pre- and postoperative occlusal radiography, inconsistent orthodontic management and a lack of prospective data collection. An 81% success rate for alveolar bone grafting compares favourably to the CSAG study. Of 82 patients, 68 had sufficient data for a retrospective review; 21 were our own patients and 47 were referred into the centralised service. The success of bone grafting as defined by CSAG (including Bergland scores) is based on only two-thirds of the patients as many have their orthodontic treatment managed in more distant units and radiographs are much harder to obtain. Bone grafting later than age 11 years, was true for 28% (6/21) of our BCH patients and 46% (22/47) for those referred to our service. CONCLUSIONS: This audit demonstrates what has been achieved in a re-organised service in the context of Real Politik in the NHS and suggests the areas that require improvement.