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The influenza virus continues to pose a significant threat to public health throughout the world. Current avian influenza outbreaks in humans have heightened the need for improved surveillance and planning. Despite recent advances in the development of vaccines and antiviral drugs, seasonal epidemics of influenza continue to contribute significantly to general practitioner workloads, emergency hospital admissions, and deaths. In this paper we review data produced by the Royal College of General Practitioners Weekly Returns Service, a sentinel general practice surveillance network that has been in operation for over 40 years in England and Wales. We show a gradually decreasing trend in the incidence of respiratory illness associated with influenza virus infection (influenza-like illness; ILI) over the 40 years and speculate that there are limits to how far an existing virus can drift and yet produce substantial new epidemics. The burden of disease caused by influenza presented to general practitioners varies considerably by age in each winter. In the pandemic winter of 1969/70 persons of working age were most severely affected; in the serious influenza epidemic of 1989/90 children were particularly affected; in the millennium winter (in which the NHS was severely stretched) ILI was almost confined to adults, especially the elderly. Serious confounders from infections due to respiratory syncytial virus are discussed, especially in relation to assessing influenza vaccine effectiveness. Increasing pressure on hospitals during epidemic periods are shown and are attributed to changing patterns of health-care delivery. [ABSTRACT FROM AUTHOR]

Background: The WHO have set health standards in the form of 21 targets Health 21 - and the EU are developing a set of health indicators whereby national health status can be measured. Data from Slovenia and from England and Wales assessing information systems in primary care and their capacity to deliver the requirements of these initiatives have been examined. In both countries, primary care is provided through a state-led service. Methods: Consultation data from the annual report of the Department of Health Slovenia (1999) are compared in respect of relevant targets with data from the Fourth National Morbidity Survey (1992) in England and Wales. Consultation rates were standardized to the European Union 15 country population (1998). Results: Consultation rates in females were similar in the two countries whereas in males rates were higher in Slovenia. The proportionate distributions of consultations by chapter of the International Classification of Diseases (ICD) were similar in both countries, respiratory (17%) and musculoskeletal (9%) disorders ranked first and second. For eye diseases, injury and poisoning, factors influencing health status (e.g. medical examination), proportions were higher in Slovenia: for mental disorders higher in England and Wales. The relativity of male to female consultation rates was broadly similar with higher rates in females in most ICD chapters. These differences are considered in detail against the background of WHO targets. Conclusions: Data gathered systematically from the surveillance of consultations in primary care are important to the measurement of WHO 'Health 21' targets. [ABSTRACT FROM AUTHOR]

Background: In recent years there has been an increasing emphasis on the delivery of preventive care in general practice. At the same time, available evidence suggests people from lower social classes receive less preventive care compared with people from higher social class. The objective of this study was to assess the uptake of screening by blood pressure measurement, cervical cytology and manual breast examination in risk populations by patients attending their general practitioners and relate the findings to levels of educational attainment and type of health insurance. Methods: The study was based on data gathered in the Dutch National Survey of General Practice in which 161 GPs recorded sociodemographic data, reasons for encounter, diagnoses and interventions during a 3 month period. Persons receiving the above procedures as screening measures were counted and expressed as rates per 1,000 persons registered and per 1,000 persons consulting. These rates were examined at three levels of educational attainment and according to the health insurance of the patient using logistic regression methods. Results: When analysed by educational attainment, high levels of blood pressure measurement were found in persons of lower educational attainment in both males and females (30-59 years) while for cervical cytology (35-54 years) higher levels were found amongst the better educated and for breast examination (40-69 years) the rates were similar regardless of educational attainment. When analysed by insurance status parallel trends were observed, with higher rates for blood pressure measurement among the publicly insured and higher rates for cervical cytology among the privately insured. Conclusions: The results, whether based on persons registered or persons consulting, suggest no important social bias in the extent to which persons are screened by blood pressure measurement or breast examination. There were strong social gradients for cervical cytology favouring the better educated and privately insured. More effective targeting of women with low educational attainment and publicly insured is called for. [ABSTRACT FROM AUTHOR]

Background: A key component of strategies to reduce antimicrobial resistance is better antimicrobial prescribing. The majority of antibiotics are prescribed in primary care. While many existing surveillance systems can monitor trends in the quantities of antibiotics prescribed in this setting, it can be difficult to monitor the quality of prescribing as data on the condition for which prescriptions are issued are often not available. We devised a standardized methodology to facilitate the monitoring of condition-specific antibiotic prescribing in primary care., Methods: We used a large computerized general practitioner database to develop a standardized methodology for routine monitoring of antimicrobial prescribing linked to clinical indications in primary care in the UK. Outputs included prescribing rate by syndrome and percentages of consultations with antibiotic prescription, for recommended antibiotic, and of recommended treatment length., Results: The standardized methodology can monitor trends in proportions of common infections for which antibiotics were prescribed, the specific drugs prescribed and duration of treatment. These data can be used to help assess the appropriateness of antibiotic prescribing and to assess the impact of prescribing guidelines., Conclusions: We present a standardized methodology that could be applied to any suitable national or local database and adapted for use in other countries.

We studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. Virus detections [A(H3N2), B, A(H1N1)] and clinical incidence of influenza-like illness (ILI) in 12·3 million person-years in the long-running Royal College of General Practitioners-linked clinical-virological surveillance programme in England & Wales were examined. The number of days between symptom onset and the all-age peak ILI incidence were compared by age group for each influenza type/subtype. We found that virus detection and ILI incidence increase, peak and decrease were in unison. The mean interval between symptom onset to peak ILI incidence in virus detections (all ages) was: A(H3N2) 20·5 [95% confidence interval (CI) 19·7-21·6] days; B, 18·8 (95% CI 15·8·0-21·7) days; and A(H1N1) 17·0 (95% CI 15·6-18·4) days. Differences by age group were examined using the Kruskal-Wallis test. For A(H3N2) and A(H1N1) viruses the interval was similar in each age group. For influenza B there were highly significant differences by age group (P = 0·0001). Clinical incidence rates of ILI reported in the 8 weeks preceding the period of influenza virus activity were used to estimate a baseline incidence and threshold value (upper 95% CI of estimate) which was used as a marker of epidemic progress. Differences between the age groups in the week in which the threshold was reached were small and not localized to any age group. In conclusion we found no evidence to suggest that influenza A(H3N2) and A(H1N1) occurs in the community in one age group before another. For influenza B, virus detection was earlier in children aged 5-14 years than in persons aged ⩾25 years.

Background: Influenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination., Methods: Weekly age specific data on hospital admissions (1997-2009) and on deaths (1997-2009) were obtained from national databases. Virology reports (1996-2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as 'respiratory disease broadly defined'. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes)., Results: In the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza-attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5-17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50-64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk., Conclusions: Our study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5-17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group., Trial Registration: ClinicalTrial.gov, NCT01520935.

Objective: The burden of respiratory syncytial virus (RSV) illness is not well characterised in primary care. We estimated the burden of disease attributable to RSV in children in the UK between 1995 and 2009., Design: Time-series regression modelling., Setting: A multiple linear regression model based on weekly viral surveillance (RSV and influenza, Public Health England), and controlled for non-specific seasonal drivers of disease, estimated the proportion of general practitioner (GP) episodes of care (counted as first visit in a series within 28 days; Clinical Practice Research Datalink, CPRD), hospitalisations (Hospital Episode Statistics, HES) and deaths (Office of National Statistics, ONS) attributable to RSV each season., Participants: Children 0-17 years registered with a GP in CPRD, or with a respiratory disease outcome in the HES or ONS databases., Primary Outcome Measures: RSV-attributable burden of GP episodes, hospitalisations and deaths due to respiratory disease by age. RSV-attributable burden associated with selected antibiotic prescriptions., Results: RSV-attributable respiratory disease in the UK resulted in an estimated 450 158 GP episodes, 29 160 hospitalisations and 83 deaths per average season in children and adolescents, with the highest proportions in children <6 months of age (14 441/100 000 population, 4184/100 000 and 6/100 000, respectively). In an average season, there were an estimated 125 478 GP episodes for otitis media and 416 133 prescriptions for antibiotics attributable to RSV. More GP episodes, hospitalisations and deaths from respiratory disease were attributable to RSV than to influenza in children under 5 years., Conclusions: The burden of RSV in children in the UK exceeds that of influenza. RSV in children and adolescents contributes substantially to GP office visits for a diverse range of illnesses, and was associated with an average 416 133 prescribed antibiotic courses per season. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children., Trial Registration Number: NCT01706302., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Background: Growing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data., Methods: Multiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302 . Registered 11 October 2012., Results: Among adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza., Conclusion: RSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly.

Influenza B represents a high proportion of influenza cases in some seasons (even over 50%). The Influenza B study in General Practice (IBGP) is a multicenter study providing information about the clinical, demographic and socio-economic characteristics of patients affected by lab-confirmed influenza A or B. Influenza B patients and age-matched influenza A patients were recruited within the sentinel surveillance networks of France and Turkey in 2010-11 and 2011-12 seasons. Data were collected for each patient at the swab test day, after 9±2 days and, if not recovered, after 28±5 days. It was related to patient's characteristics, symptoms at presentation, vaccination status, prescriptions of antibiotics and antivirals, duration of illness, follow-up consultations in general practice or emergency room. We performed descriptive analyses and developed a multiple regression model to investigate the effect of patients and disease characteristics on the duration of illness. Overall, 774 influenza cases were included in the study: 419 influenza B cases (209 in France and 210 in Turkey) and 355 influenza A cases (205 in France and 150 in Turkey). There were no differences between influenza A and B patients in terms of clinical presentation and number of consultations with a practitioner; however, the use of antivirals was higher among influenza B patients in both countries. The average (median) reported duration of illness in the age groups 0-14 years, 15-64 years and 65+ years was 7.4 (6), 8.7 (8) and 10.5 (9) days in France, and 6.3 (6), 8.2 (7) and 9.2 (6) days in Turkey; it increased with age but did not differ by virus type; increased duration of illness was associated with antibiotics prescription. In conclusion, our findings show that influenza B infection appears not to be milder disease than influenza A infection.

This report aims to evaluate the usefulness of self-sampling as an approach for future national surveillance of emerging respiratory infections by comparing virological data from two parallel surveillance schemes in England. Nasal swabs were obtained via self-administered sampling from consenting adults (≥ 16 years-old) with influenza symptoms who had contacted the National Pandemic Flu Service (NPFS) health line during the 2009 influenza pandemic. Equivalent samples submitted by sentinel general practitioners participating in the national influenza surveillance scheme run jointly by the Royal College of General Practitioners (RCGP) and Health Protection Agency were also obtained. When comparable samples were analysed there was no significant difference in results obtained from self-sampling and clinician-led sampling schemes. These results demonstrate that self-sampling can be applied in a responsive and flexible manner, to supplement sentinel clinician-based sampling, to achieve a wide spread and geographically representative way of assessing community transmission of a known organism.

Objectives: To measure trends in antibiotic prescribing in UK primary care in relation to nationally recommended best practice., Patients and Methods: A descriptive study linking individual patient data on diagnosis and prescription in a large primary care database, covering 537 UK general practices during 1995-2011., Results: The proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in 2011. There was marked variation by primary care practice in 2011 [10th-90th percentile range (TNPR) 32%-65%]. Antibiotic prescribing for sore throats fell from 77% in 1995 to 62% in 1999 and then stayed broadly stable (TNPR 45%-78%). Where antibiotics were prescribed for sore throat, recommended antibiotics were used in 69% of cases in 2011 (64% in 1995). The use of recommended short-course trimethoprim for urinary tract infection (UTI) in women aged 16-74 years increased from 8% in 1995 to 50% in 2011; however, a quarter of practices prescribed short courses in ≤16% of episodes in 2011. For otitis media, 85% of prescriptions were for recommended antibiotics in 2011, increasing from 77% in 1995. All these changes in annual prescribing were highly statistically significant (P < 0.001)., Conclusions: The implementation of national guidelines in UK primary care has had mixed success, with prescribing for coughs/colds, both in total and as a proportion of consultations, now being greater than before recommendations were made to reduce it. Extensive variation by practice suggests that there is significant scope to improve prescribing, particularly for coughs/colds and for UTIs., (© Crown copyright 2014.)

Background: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries., Methods and Findings: We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012)., Conclusions: We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.

Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage rates to higher levels (i.e., above 70-80%) have been ineffective in highly developed countries where the vaccine is used, hindered by the public's skepticism towards vaccines in general. New educational and social media methods to increase vaccine acceptance and coverage were discussed. While the first priority should be the development of improved influenza vaccines, a particular focus on the aging global population is critical. It is also important to draw lessons from other academic disciplines that can help to inform vaccine education programs, policy, and communication. By tailoring communications and patient education using an understanding of cognitive bias and the model of preferred cognitive styles, the likelihood of effecting desirable health decisions can be maximized, leading to improved vaccine coverage and control of influenza and other vaccine-preventable diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42-66); age-specific adjusted VE was 87% (95% CI 45-97) in <5-year-olds and 84% (95% CI 27-97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI -6 to 51) overall and 72% (95% CI 15-91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42-68) and in 5- to 14-year-olds 75% (95% CI 32-91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.

The 2011/12 season was characterised by unusually late influenza A (H3N2) activity in the United Kingdom (UK). We measured vaccine effectiveness (VE) of the 2011/12 trivalent seasonal influenza vaccine (TIV) in a test-negative case–control study in primary care. Overall VE against confirmed influenza A (H3N2) infection, adjusted for age, surveillance scheme and month, was 23% (95% confidence interval (CI): -10 to 47). Stratified analysis by time period gave an adjusted VE of 43% (95% CI: -34 to 75) for October 2011 to January 2012 and 17% (95% CI: -24 to 45) for February 2012 to April 2012. Stratified analysis by time since vaccination gave an adjusted VE of 53% (95% CI: 0 to 78) for those vaccinated less than three months, and 12% (95% CI: -31 to 41) for those vaccinated three months or more before onset of symptoms (test for trend: p=0.02). For confirmed influenza B infection, adjusted VE was 92% (95% CI: 38 to 99). A proportion (20.6%) of UK influenza A(H3N2) viruses circulating in 2011/12 showed reduced reactivity (fourfold difference in haemagglutination inhibition assays) to the A/Perth/16/2009 2011/12 vaccine component, with no significant change in proportion over the season. Overall TIV protection against influenza A(H3N2) infection was low, with significant intraseasonal waning.

The early experience of the United Kingdom (UK) is that influenza B has dominated the influenza 2012/13 season. Overall trivalent influenza vaccine (TIV) adjusted vaccine effectiveness (VE) against all laboratory-confirmed influenza in primary care was 51% (95% confidence interval (CI): 27% to 68%); TIV adjusted VE against influenza A alone or influenza B alone was 49% (95% CI: -2% to 75%) and 52% (95% CI: 23% to 70%) respectively. Vaccination remains the best protection against influenza.

Estimation of influenza vaccine effectiveness (VE) is complicated by various degrees of mismatch between circulating and vaccine strains each season. We carried out a cohort study to estimate VE of trivalent (TIV) and pandemic influenza vaccines (PIV) in preventing various respiratory outcomes among general practice (GP) patients in England and Wales between 2008 and 2010. Dates of consultations for influenza-like illness (ILI), acute respiratory tract infection (ARTI), lower respiratory tract infection (LRTI) and nasopharyngeal swabs were obtained from the patient-level electronic records of the 100 practices enrolled in a national GP network. Dates of vaccination with TIV and PIV were also extracted. Confounders including age, time period and consultation frequency were adjusted for through Poisson regression models. In the winter of 2008/9, adjusted VE of TIV in preventing ILI was 22.3% (95% CI 13.5%, 30.2%). During the 2009/10 winter VE for PIV in preventing ILI was 21.0% (5.3%, 34.0%). The VE for PIV in preventing PCR-confirmed influenza A/H1N1 (2009) was 63.7% (-6.1%, 87.6%). TIV during the period of influenza circulation of 2008/9 and PIV in the winter of 2009/10 were effective in preventing GP consultations for ILI. The cohort study design could be used each season to estimate VE; however, residual confounding by indication could still present issues, despite adjustment for propensity to consult., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We review experience in England of the swine flu pandemic between May 2009 and April 2010. The surveillance data from the Royal College of General Practitioners Weekly Returns Service and the linked virological data collected in the integrated program with the Health Protection Agency are used as a reference frame to consider issues emerging during the pandemic. Ten lessons are summarized. (1) Delay between illness onset in the first worldwide cases and virological diagnosis restricted opportunities for containment by regional prophylaxis. (2) Pandemic vaccines are unlikely to be available for effective prevention during the first wave of a pandemic. (3) Open, realistic and continuing communication with the public is important. (4) Surveillance programs should be continued through summer as well as winter. (5) Severity of illness should be incorporated in pandemic definition. (6) The reliability of diagnostic tests as used in routine clinical practice calls for further investigation. (7) Evidence from serological studies is not consistent with evidence based on health care requests made by sick persons and is thus of limited value in cost effectiveness studies. (8) Pregnancy is an important risk factor. (9) New strategies for administering vaccines need to be explored. (10) Acceptance by the public and by health professionals of influenza vaccination as the major plank on which the impact of influenza is controlled has still not been achieved.

This study provides mid-season estimates of the effectiveness of 2010/11 trivalent influenza vaccine and previous vaccination with monovalent influenza A(H1N1)2009 vaccine in preventing confirmed influenza A(H1N1)2009 infection in the United Kingdom in the 2010/11 season. The adjusted vaccine effectiveness was 34% (95% CI: -10 - 60%) if vaccinated only with monovalent vaccine in the 2009/10 season; 46% (95% CI: 7 - 69%) if vaccinated only with trivalent influenza vaccine in the 2010/11 season and 63% (95% CI: 37 - 78%) if vaccinated in both seasons.

Following the global spread of pandemic influenza A(H1N1)2009, several pandemic vaccines have been rapidly developed. The United Kingdom and many other countries in the northern hemisphere implemented seasonal and pandemic influenza vaccine programmes in October 2009. We present the results of a case–control study to estimate effectiveness of such vaccines in preventing confirmed pandemic influenza infection. Some 5,982 individuals with influenza-like illness seen in general practices between November 2009 and January 2010 were enrolled. Those testing positive on PCR for pandemic influenza were assigned as cases and those testing negative as controls. Vaccine effectiveness was estimated as the relative reduction in odds of confirmed infection between vaccinated and unvaccinated individuals. Fourteen or more days after immunisation with the pandemic vaccine, adjusted vaccine effectiveness (VE) was 72% (95% confidence interval (CI): 21% to 90%). If protection was assumed to start after seven or more days, the adjusted VE was 71% (95% CI: 37% to 87%). Pandemic influenza vaccine was highly effective in preventing confirmed infection with pandemic influenza A(H1N1)2009 from one week after vaccination. No evidence of effectiveness against pandemic influenza A(H1N1)2009 was found for the 2009/10 trivalent seasonal influenza vaccine (adjusted VE of -30% (95% CI: -89% to 11%)).

Background: Estimation of influenza vaccine effectiveness (V/E) is needed early during influenza outbreaks in order to optimise management of influenza--a need which will be even greater in a pandemic situation., Objective: Examine the potential of routinely collected virological surveillance data to generate estimates of V/E in real-time during winter seasons., Methods: Integrated clinical and virological community influenza surveillance data collected over three winters 2004/5-2006/7 were used. We calculated the odds of vaccination in persons that were influenza-virus-positive and the odds in those that were negative and provided a crude estimate of V/E. Logistic regression was used to obtain V/E estimates adjusted for confounding variables such as age., Results: Multivariable analysis suggested that adjustments to the crude V/E estimate were necessary for patient age and month of sampling. The annual adjusted V/E was 2005/6, 67% (95% CI 41% to 82%); 2006/7 55% (26% to 73%) and 2007/8 67% (41% to 82%). The adjusted V/E in persons <65 years was 70% (57% to 78%) and 65 years and over 46% (-17% to 75%). Estimates differed by small insignificant amounts when calculated separately for influenza A and B; by interval between illness onset and swab sample; by analysis for the period November to January in each year compared with February to April and according to viral load., Conclusion: We have demonstrated the potential of using routine virological and clinical surveillance data to provide estimates of V/E early in season and conclude that it is feasible to introduce this approach to V/E measurement into evaluation of national influenza vaccination programs.

Statins reduce cardiovascular mortality and related risks associated with pneumonia suggesting potentially beneficial use in influenza pandemics. We investigated the effect of current statin use on acute respiratory infections in primary care. Data from anonymized electronic medical records of persons aged 45 years were examined for statin use, chronic morbidity, respiratory diagnoses, vaccination procedures, and immune suppression. Logistic regression models were used to calculate odds ratios (ORs) for statin users vs. non-users in respiratory infection outcomes. A total of 329 881 person-year observations included 18% statin users and 46% influenza vaccinees. Adjusted ORs for statin users vs. non-users were: influenza-like illness, 1.05 (95% CI 0.92-1.20); acute bronchitis, 1.08 (95% CI 1.01-1.15); pneumonia, 0.91 (95% CI 0.73-1.13); all acute respiratory infections, 1.03 (95% CI 0.98-1.07); and urinary tract infections, 0.91 (95% CI 0.85-0.98). We found no benefit in respiratory infection outcomes attributable to statin use, although uniformly higher ORs in non-vaccinated statin users might suggest synergism between statins and influenza vaccination.

Background: The representativeness of practice networks is important when using the information obtained to guide health policy., Aim: To develop a model for examining the representativeness of practice networks., Methods: Comparison of surveyed population, practice structure and prescribing characteristics with the national data using the Weekly Returns Service (WRS) for 2006 as an example of practice network. The population monitored was compared with the national PCT population. The practice postcode was linked to the Index of Multiple Deprivation and the distribution compared with the national equivalents. Doctor and practice-specific structural data (obtained by questionnaire) and practice-prescribing data were compared with the national equivalents. The significance of differences was evaluated using non-parametric tests., Results: The WRS population was closely matched with the national data by age, gender and deprivation index. Compared with the national equivalents, WRS practices, included more younger GPs, had a larger average list per GP and fewer practices with a list of less than 1499 per GP. Prescribing patterns were similar to their PCT equivalents excepting for small reductions of antibacterial prescribing (items 7% and cost 5%)., Conclusion: We demonstrate a low-cost model methodology for examining the representativeness of practice networks using independent data with minimum practice input.

Background: In the northern hemisphere winter of 2003-04 antigenic variant strains (A/Fujian/411/02 -like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children., Methodology/principal Findings: Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003-04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged., Conclusions/significance: This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood.

The incidence and causes of infectious intestinal disease (IID) in children aged <5 years presenting to general practitioners (GPs) were estimated. During a 12-month period, soiled nappies were collected from children presenting with symptoms suggestive of IID in a network of 65 GPs located across England. Molecular methods were used to detect a range of enteric pathogens including viruses, bacteria and parasites. Genotyping was performed on rotavirus and norovirus isolates. A total of 583 nappies were collected from 554 children; a pathogen was detected in 361 (62%) specimens. In the 43 practices 1584 new episodes of IID were recorded in a population averaging 19774; the specimen capture rate was 28%. IID incidence peaked during March and April. Norovirus (24.5%), rotavirus (19.0%) and sapovirus (12.7%) were most commonly detected, and mixed infections were detected in 11.7% of cases. Strain characterization revealed G1P[8] (65.8%), G4P[4] (8.1%) and G9P[8] (8.1%) as the most common rotavirus genotypes, similar to the UK national distribution. GII-3 (42.9%) and GII-4 (39.7%) were the most common norovirus genotypes; this was significantly different (P<0.005) to the national distribution.

Annual vaccination of all children 6-59 months of age is recommended in the United States but not in most of Europe. This paper reviews issues surrounding the epidemiology of influenza and vaccine effectiveness relevant to the determination of vaccination policy. Most clinical trials of vaccines (and treatments) that provide the evidence for current policy took place in the 1990s when rates of influenza-like illness (ILI) were twice those reported in recent years. The impact of influenza in the community is concealed by the variety of diagnoses appropriate to describing acute respiratory infections. Even in influenza virus active periods diagnoses of coryza, acute bronchitis, and otitis media made by general practitioners greatly exceed those of ILI. Respiratory syncytial virus presents particular problems because it often circulates at the same time as influenza. Thus, the diagnostic uncertainty and variety of respiratory pathogens causing similar illnesses are major confounders when estimating influenza vaccine effectiveness. Although meta-analyses have cast doubt on the wisdom of the universal vaccination of children, high-quality clinical trials have demonstrated efficacy against laboratory-confirmed infection. The distinction between this positive benefit and the wider issue of effectiveness against ILI in the community poses difficulties for determining policy. Mathematical models examining this issue are populated with data that are mostly estimated: therefore, the sensitivity analysis is critical and the conclusions are invariably accompanied by reservations. National policies based on demonstrated cost effectiveness are desirable, but these should not become a barrier to parents wishing to secure a benefit for their child or family, provided there is clear evidence of clinical efficacy.

Respiratory infections are one of the leading causes of morbidity and mortality worldwide: influenza and respiratory syncytial virus (RSV) are the predominant pathogens responsible. Annual vaccination and the use of antiviral drugs provides both protection and treatment against influenza, particularly protecting those patients most at risk, including the elderly and individuals with chronic comorbidities. Currently, there are extremely limited options in the protection against RSV infection, making those at-risk patients vulnerable to serious disease, complications and death. This review focuses on recent trends in respiratory illness in the elderly, particularly focusing on the burden of influenza and RSV on hospitalizations and mortality. We discuss the potential benefit of influenza vaccination on these outcomes, including the recent controversial debate over the effectiveness of influenza vaccination.

Introduction: We used 3-dimensional (3D) echocardiography to identify and quantify left ventricular (LV) dyssynchrony in children with LV dysfunction compared with control subjects., Methods: The 3D echocardiography LV full volumes were acquired in 18 children, 9 with LV dysfunction and 9 control subjects. The LV was subdivided into 16 segments (apex excluded). Time from end diastole to the minimal systolic volume for each segment was expressed as a percent of the R-R interval. The SD of these times provided a 16-segment dyssynchrony index (16-SDI). The second index (12-SDI) was similarly calculated using 6 basal and 6 mid segments. The third index consisted of 6 basal segments (6-SDI)., Results: The dysfunction group exhibited significantly increased 16-SDI (P = .008) and 12-SDI (P = .01). The 16-SDI was negatively correlated with 3D ejection fraction and 2-dimensional fractional shortening., Conclusions: Children with LV dysfunction demonstrate increased intraventricular LV dyssynchrony by 3D echocardiography, in a pattern that is negatively correlated with LV systolic function.

Background: Hospitals experience winter surges in admissions due to respiratory infections. The roles of acute bronchitis and influenza-like illness (ILI) in the timing and severity of these surges are examined over the years 1990-91 to 2004-05., Methods: Respiratory admissions of persons aged > or =65 years in England and Wales were analysed in relation to patients with ILI or acute bronchitis diagnosed by community-based general practitioners from a sentinel surveillance network., Results: Acute bronchitis and ILI accounted for 46 and 7% of the variation in respiratory admissions, respectively: when admissions were lagged by 1 week, these estimates were 20 and 14%, respectively. Admissions peaked in weeks 52, 01 or 02 (late December to early January) in 14 of the 15 winters. Acute bronchitis peaked during weeks 01 or 02; ILI exhibited greater variability and peaks ranged from weeks 46 (mid-November) to 07 (mid-February). During winters where acute bronchitis and ILI peaked concurrently, surges on hospitals were most severe., Conclusions: During each winter acute bronchitis provides a consistent and major contribution to the winter admissions surge in the elderly. The variable incidence of ILI can increase the surge in admissions, especially when ILI and acute bronchitis peak together.

We compared the burden of illness due to a spectrum of respiratory diagnostic categories among persons presenting in a sentinel general practice network in England and Wales during periods of influenza and of respiratory syncytial virus (RSV) activity. During all periods of viral activity, incidence rates of influenza-like illness, bronchitis and common cold were elevated compared to those in baseline periods. Excess rates per 100,000 of acute bronchitis were greater in children aged <1 year (median difference 2702, 95% CI 929-4867) and in children aged 1-4 years (994, 95% CI 338-1747) during RSV active periods rather than influenza; estimates for the two viruses were similar in other age groups. Excess rates of influenza-like illness in all age groups were clearly associated with influenza virus activity. For common cold the estimates of median excess rates were significantly higher in RSV active periods for the age groups <1 year (3728, 95% CI 632-5867) and 5-14 years (339, 95% CI 59-768); estimates were similar in other age groups for the two viruses. The clinical burden of disease associated with RSV is as great if not greater than influenza in patients of all ages presenting to general practitioners.

This article summarizes personal reflections from the perspective of general practice on developments with regard to antibiotic resistance and the containment of antibiotic prescribing during the lifetime of the Specialist Advisory Committee on Antimicrobial Resistance in England. These reflections concern the entry of antibiotics into the food chain, recent extensions of prescribing responsibilities and developments towards improved surveillance and reduced antibiotic prescribing. A large gap remains between the scientific appreciation of the risks from antimicrobial resistance and effective means to measure it and thereby hopefully control it.

Background: Reductions in the number of dispensed antibiotics and the incidence of respiratory infections presented to GPs and have been reported. Whether this trend applies to skin infections requires further investigation., Aim: To examine trends in the incidence of skin infections in relation to trends in dispensed prescriptions for flucloxacillin, topical fusidic acid, mupirocin, and corticosteroids with fusidic acid., Design of Study: Population-based analysis of patients presenting to GPs (1999-2005) contrasted with national prescribing data., Setting: A sentinel practice network covering a population of 700,000 in England and Wales., Method: Quarterly incidence rates of skin infections and of impetigo reported over the years 1999-2005 were compared with quarterly data on dispensed prescriptions reported by the Prescription Pricing Authority for England., Results: In children (aged 0-14 years) the incidence of skin infections decreased slightly between 1999 and 2003 and more sharply from 2004 to 2005. In adults (aged > or =15 years) incidence was reasonably constant from year to year. In every year examined, and in both age groups, there were autumnal incidence peaks. There were annual increases in dispensed prescriptions for flucloxacillin capsules, but there was little change in the use of flucloxacillin syrups and topical antibiotic prescriptions. All prescribing data sets showed increases in the third quarter: topical corticosteroids with fusidic acid were prescribed more frequently in summer than winter., Conclusion: In spite of slight reductions in the incidence of skin infections, flucloxacillin capsule-dispensed prescriptions have increased, suggesting that doctors have not limited their antibiotic prescribing behaviour for skin conditions.