Cost-impact study of rotavirus vaccination programme in Scotland.

Aim: In July 2013, the Scottish Government introduced a rotavirus vaccination programme into the childhood immunisation schedule. The aim of this research was to estimate the cost-impact of this programme. Methods: Data for rotavirus-related resource use were identified including laboratory reports, hospitalisations, attendances at accident and emergency departments (A&E), general practice consultations (GP), calls to the National Health Service telephone helpline (NHS24) and prescriptions for common rehydration treatments. We used an interrupted time series analysis approach to assess the impact on resource utilisation in all categories. Appropriate costs were added to the models and predicted pre-and post-vaccination mean annual costs were estimated. The cost of the vaccination programme was estimated using costs from the literature. Results: The vaccination programme was associated with a reduction in utilisation in all measured healthcare resource categories. These reductions were all statistically significant (at the 95% level) with p-values less than 0.001. Reductions ranged from 18% in calls to NHS24 to 73% in positive laboratory reports. The vaccination programme was associated with a reduction in annual healthcare resource costs of 38% (£595,000 per 100,000 infants < 5 years old) in our measured categories (including £495,000 from a reduction in hospital stays). The annual overall cost-impact of the rotavirus vaccination programme (the cost of delivering the programme minus the reduction in resource costs) was estimated at approximately £435,000 per 100,000 infants < 5 years old. Conclusion: The rotavirus vaccination programme was associated with a reduction in all measured categories of rotavirus-related resource use by infants < 5 years old.

Evidence-Based Medicine applied to the control of communicable disease incidents when evidence is scarce and the time is limited.

Control of acute communicable disease incidents demands rapid risk assessment, often with minimal peer-reviewed literature available but conducted in the public's view. This paper explores how methods of evidence-based medicine (EBM) can be applied in this scenario to improve decision making and risk communication. A working group with members from EBM organisations, public health institutions and the European Centre for Disease Prevention and Control used a six-stage framework for rapid risk assessments: preparation, risk detection/verification, risk assessment, development of advice, implementation, and evaluation. It concluded that data from observational studies, surveillance and modelling play a vital role in the evidence base. However, there is a need to further develop protocols and standards, to perform, report and register outbreak investigations more systematically and rigorously, and to allow rapid retrieval of the evidence in emergencies. Lack of evidence for risk assessment and advice (usual for new and emerging diseases) should be made explicit to policy makers and the public. Priorities are to improve templates for reporting and assessing the quality of case and outbreak reports, apply grading systems to evidence generated from field investigations, improve retrieval systems for incident reports internationally, and assess how to communicate uncertainties of scientific evidence more explicitly.

Automated mortality monitoring in Scotland from 2009.

Mortality monitoring systems are important for gauging the effect of influenza and other wide ranging health threats. We present the daily all-cause mortality monitoring system routinely used in Scotland, which differs from others by using two different statistical models for calculating expected mortality. The first model is an extended Serfling model, which captures annual seasonality in mortality using sine and cosine terms, and is frequently seen in other systems. Serfling models fit to summer seasonality well, but not to the winter peak. Thus, during the winter, there are frequent 'excesses', higher than expected mortality, making it harder to directly judge if winter mortality is higher than in previous years. The second model, a Generalised Additive Model, resolves this by allowing a more flexible seasonal pattern that includes the winter peak. Thus, excesses under the second model directly indicate if winter mortality is higher than in previous years, useful, for example, in judging if a new strain of seasonal influenza is more likely to produce death than previous ones. As common in all-cause mortality monitoring systems, the Scottish system uses a reporting delay correction: we discuss the difficulties of interpretation when such a correction is used and possible avenues for future work that may address these difficulties.

Choice of anaesthetic agents for caesarean section: a UK survey of current practice.

BACKGROUND: A national survey of current practice and preferred drug choices for both induction and maintenance of general anaesthesia for caesarean section was undertaken. METHODS: Following approval by the Obstetric Anaesthetists' Association, all UK consultant members were invited to respond to an electronic survey. RESULTS: The response rate was 56% (691/1228). Ninety-three percent of respondents use thiopental for induction: 58% (15% definitely and 44% probably) would support a change to propofol for induction. Thiopental was used in most cases for historical reasons (37%) or to reduce awareness (31%); other considerations included a clear end-point, dose predictability, cardiovascular stability, effects on the baby and drug licence concerns. Fifty-seven percent indicated that their trainees were encouraged to use thiopental for non-obstetric anaesthesia. Fifteen percent of respondents use opioids during rapid-sequence induction. Eighty-five percent use nitrous oxide; 53% of respondents use sevoflurane (51.6%) or desflurane (1.6%) for maintenance of anaesthesia, and this would increase to over 80% if financial constraints were removed. CONCLUSION: Our survey suggests that while thiopental remains the induction agent of choice in the UK, a reasonable body of medical opinion would support a change to propofol for induction. This is reassuring as thiopental becomes more difficult and expensive to obtain.

The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function.

Disrupted in schizophrenia 1 (DISC1), a genetic risk factor for multiple serious psychiatric diseases including schizophrenia, bipolar disorder and autism, is a key regulator of multiple neuronal functions linked to both normal development and disease processes. As these diseases are thought to share a common deficit in synaptic function and architecture, we have analyzed the role of DISC1 using an approach that focuses on understanding the protein-protein interactions of DISC1 specifically at synapses. We identify the Traf2 and Nck-interacting kinase (TNIK), an emerging risk factor itself for disease, as a key synaptic partner for DISC1, and provide evidence that the DISC1-TNIK interaction regulates synaptic composition and activity by stabilizing the levels of key postsynaptic density proteins. Understanding the novel DISC1-TNIK interaction is likely to provide insights into the etiology and underlying synaptic deficits found in major psychiatric diseases.

Quantitative measurement of the efficacy of protein removal by cleaning formulations; comparative evaluation of prion-directed cleaning chemistries.

The stability of the infectious agent causing variant Creutzfeldt-Jakob disease (vCJD) has highlighted the importance of cleaning surgical instruments for controlling potential spread of iatrogenic CJD. In this study, thermostable adenylate kinases (tAKs) in test soil were coated on to stainless steel and these surrogate agents used to evaluate the efficacy of a range of cleaning chemistries in a bench-top washer disinfector (btWD), or as a pre-soak either with or without subsequent treatment by btWD. Two tAKs were tested initially for ease of removal, the most persistent being Sulfolobus acidocaldarius-derived tAK which was used for evaluating the cleaning chemistries. Conventional chemistries were generally more effective when used in a btWD than as pre-soaks. Cleaning efficacy improved when pre-soaks were followed by treatment with intermediate performing enzymes, demonstrating greater than additive effect on residual tAK activity. Three of the four prion-directed chemistries reduced residual tAK activity to below the limit of quantification (LoQ) by more than 4.8 log(10); <175pg tAK remaining as a pre-soak alone. A conventional alkaline cleaning product also reduced residual tAK activity to below the LoQ but only when used in a btWD. tAK soil dried on to the device was removed less efficiently than tAK soil still moist on the device, with a 320-fold and 28-fold increase in residual tAK activity for pre-soak and btWD, respectively. The study demonstrated the potential for a tAK indicator to describe the effectiveness of protein removal using different chemistries or treatment processes.

Decontamination of prion protein (BSE301V) using a genetically engineered protease.

A previous study has demonstrated the potential of alkaline proteases to inactivate bovine spongiform encephalopathy (BSE301V). Here we explored the use of MC3, a genetically engineered variant of Bacillus lentus subtilisin. MC3 was used to digest BSE301V infectious mouse brain homogenate (iMBH). MC3 eliminated all detectable 6H4-immunoreactive material at pH 10 and 12; however, Proteinase K was only partially effective at pH 12. When bioassayed in VM mice, MC3- and Proteinase K-digested iMBH gave respectively 66.6% and 22.7% survival rates. Using a titration series for disease incubation, this equates to a >7log reduction in infectivity for MC3 and >6log reduction for Proteinase K. This study demonstrates the potential for thermostable proteases to be developed as effective inactivation processes for prion agents in healthcare management.

Surface decontamination of surgical instruments: an ongoing dilemma.

The issues of cross-infection and the survival of variant Creutzfeldt Jakob disease (vCJD) on surgical instruments have highlighted the importance of cleanliness of multiple-use surgical instruments. The aim of this study was to assess the levels of total protein contamination on a wide range of surgical instruments as an indication of the effectiveness of routine cleaning and disinfection in hospitals. Anonymized trays of wrapped and autoclaved instruments were supplied to two laboratories for analysis at the stage where they would normally be returned to operating theatres. Instruments were assessed for residual protein and total organic matter. Laboratory A showed that 17% (35/206) of instruments were above a threshold that equated to 200 microg. The worst examples, a McIvor gag, a Draffin rod (child) and a Yankaur sucker, had 1.028, 1.286 and 2.228 mg of extractable protein, respectively. The median (25th, 75th percentiles) amount of protein from instruments from different hospitals assessed in Laboratory B ranged from 8 (3, 30)mug (Hospital C) to 91 (35, 213) mug (Hospital D) (P=0.044). The residual matter washed from instruments varied from 0.62 (0.32, 0.81) mg (Hospital E) to 3.5 (3.5, 4.0) mg (Hospital A) (P=0.0001). In one case, 45 mg of residual organic matter was washed from an instrument (split stem). In conclusion, this study demonstrated that a proportion of instruments at the point of use show levels of protein that could pose a direct cross-infection risk via prion agents and other organic contamination that may reduce the effectiveness of cleaning/disinfection strategies targeted against either prions or traditional infectious agents.

Interactions between G-protein-coupled receptors and periplakin: a selective means to regulate G-protein activation.

A substantial number of G-protein-coupled receptor-interacting proteins have been identified initially by the use of yeast two-hybrid screens. Using the C-terminal tail of both opioid receptors and the melanin concentrating hormone receptor-1 as bait, the actin and intermediate filament-binding protein periplakin was isolated. In each case, the site of interaction is within helix VIII of the receptor and periplakin limits agonist-mediated G-protein activation potentially by competing with G-protein for this region of the receptor.

Prevalence, age of onset and demographic relationships of different areca nut habits amongst children in Tower Hamlets, London.

OBJECTIVE: To examine prevalence and demographic relationships of different areca nut habits amongst children. DESIGN: Self-administered questionnaire. SUBJECTS: Children aged between 11 and 15. Of 800 questionnaires distributed, 704 were fully completed (88%). SETTING: Two secondary schools in the London district of Tower Hamlets. MEASURES: Demographic, areca nut habits used, age first used, still using, frequency of use. RESULTS: Users of any areca nut habit were exclusively from the South Asian population. Of this population, 77% had engaged in a habit, and dependent upon habit between 54 and 92% of these still remained current users. The highest prevalence of current use for boys and girls respectively was for areca nut alone (36%, 43%), followed by mistee pan (35%, 29%), betel-quid (27%, 26%) and pan masala (14%, 16%). Of the current users, 44% engaged in one habit only, 24% two, 20% three and 13% all four. The highest period of risk for starting to use areca nut alone, betel-quid and mistee pan was between ages 5 and 12, whilst for pan masala it was after 10. Boys had a significantly higher risk of beginning use before 10 (P < .001) and a higher frequency of use for pan masala (P< .01), areca nut alone (P< .05) and betel-quid (P = .06) than girls. The frequency of using each habit was between 3 and 5 episodes per week, however boys use pan masala approximately 10 times per week. CONCLUSION: South Asian children may already be experienced users of areca nut. Greater attention should be directed towards identifying signs of oral submucous fibrosis, oral cancer and other potentially malignant lesions within the South Asian population.

C-axis: a growth vector for the maxilla.

Based on M-point, defined as the center of the largest circle that is tangent to the superior, anterior, and palatal outlines of the maxilla in the sagittal view, a growth axis and its direction are described for each gender from age 7.4 to 18.75 years. Growth increments along the C-axis, defined by sella-M-point, are described by regression formulas with correlation coefficients of 0.618 for females and 0.669 for males. The vector (direction) of the growth axis, defined by the angle S-M-C-axis, increases in females from 42.21 degrees at 7.4 years to 44.47 degrees at 18.75 years, with a standard deviation of 3.55 degrees. In males, it increases from a mean of 41.69 degrees at 7.6 years to 45.55 degrees at 18.6 years, with a standard deviation of 2.74 degrees. This is based on 172 serial lateral cephalograms of 20 females and 174 serial lateral cephalograms of 19 males. The C-axis incremental growth change and its vector offer a means of quantifying complex maxillary growth in the sagittal plane via cephalometric measurements relative to and coordinated with other craniofacial structures.

Stereotyped behaviors in deaf and hard of hearing children.

Stereotyped behaviors frequently cause anxiety to parents and educators, and behaviors that appear stereotyped may prompt negative reactions. There has been little research on whether deaf or hard of hearing children display such behaviors. This study surveyed 390 students aged 3-24 years attending 3 residential schools for the deaf and hard of hearing in the United Kingdom. At least 1 additional disability was reported in 79% of the students. The main findings were that: deaf and hard of hearing children without additional disabilities did not show apparently stereotyped behaviors; approximately 35% of children with additional disabilities did show such behaviors; some disabilities, in addition to hearing loss, were more likely than others to be associated with stereotyped behaviors. Implications of these findings for further research are considered with a view toward making recommendations for educational practice.