Is the onset of influenza in the community age-related?

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.

Influenza-attributable burden in United Kingdom primary care.

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.

Self-sampling for community respiratory illness: a new tool for national virological surveillance.

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.

Age-specific vaccine effectiveness of seasonal 2010/2011 and pandemic influenza A(H1N1) 2009 vaccines in preventing influenza in the United Kingdom.

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.

Vaccine effectiveness of 2011/12 trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: evidence of waning intra-seasonal protection.

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 case­control 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.

Effectiveness of pandemic and seasonal influenza vaccine in preventing pandemic influenza A(H1N1)2009 infection in England and Scotland 2009-2010.

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 case­control 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%)).

An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998-1999 to 2005-2006.

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.

The representativeness of sentinel practice networks.

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.

Seasonality and trends in the incidence and prevalence of gout in England and Wales 1994-2007.

OBJECTIVES: To examine seasonality and long-term trends in the incidence and prevalence of gout. METHODS: A retrospective study (1994-2007) using routinely collected surveillance data from the Royal College of General Practitioners Weekly Returns Service sentinel general practice network in England and Wales. New cases and acute attacks of gout per 10,000 population were calculated for age groups 0-44, 45-64, 65-74 and > or =75 years. Long-term trends of annual incidence were assessed by regression analysis. Seasonality indices were calculated using 4-weekly data, and the relative risk of gout incidence during the summer was estimated. Annual prevalence was estimated from the consulting patient population (2001-7) and from prescribing data on defined daily doses (DDD) of allopurinol (2003-7). RESULTS: The annual incidence rate of new gout cases was stable over the period 1998-2007; acute attacks decreased on average 4% per annum. New gout cases and acute attacks combined into 4-weekly incidence rates peaked during the "summer" period of each year. There was an increased risk of gout diagnosis during summer months (late April to mid-September; odds ratio 1.22, 95% CI 1.18 to 1.26). The annual prevalence of gout in 2001-7 was 0.46%, with highest rates in men > or =75 years (2.57%). Estimated prevalence based on a DDD of 400 mg allopurinol was 0.37%. CONCLUSION: The incidence of gout is seasonal. This has implications for the management of patients who currently have gout, and for those who are at risk of future attacks. The decreasing trend in the incidence of acute attacks suggests that patient management is improving.

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

Surveillance of influenza-like illness in England and Wales during 1966-2006.

We report surveillance data collected since 1966 from a general practice database in England and Wales. Incidence rates of influenza-like illness (ILI) peaked during the winter of 1969/70, and were then followed by a decade of heightened activity. There has since been a gradual downward trend of ILI, interspersed with winters of heightened activity; since 1999/2000, the incidence of ILI has been at its lowest for 40 years. We argue that the decade following the herald waves of the pandemic could be equally important for the planning of healthcare services in the community.

The measurement of morbidity in general practice.

(1) The need for morbidity data based on general practice arises because: (a) the consultation in general practice is the entry point into the health care system; (b) among the health problems brought to the attention of doctors, most are dealt with completely in general practice; (c) general practice records can provide a comprehensive database for health care. (2) The routine measurement of morbidity has to be based on "working diagnostic terms" derived by consensus amongst recorders because: (a) many episodes of illness involve only one consultation and the doctor is required to make the most of the information available to him at the time; (b) the specification of criteria would require validating evidence of conformity and this is not a realistic option on a wide scale; (c) health care data which include the opinion of the general practitioner are more valuable than data based on patient perceptions of illness. (3) The analysis and interpretation of data from general practice: (a) should preferably be based on persons as the unit of analysis; (b) when based on consultations, may be useful for examining workload, but has limited epidemiological value; (c) can, by person linkage, facilitate the study of disease concurrence; and (d) is essential for managing the health care system and monitoring the public health.

Disease concurrence in diabetes mellitus: a study of concurrent morbidity over 12 months using diabetes mellitus as an example.

STUDY OBJECTIVE: The aim was to examine disease concurrence, using diabetes mellitus as an ullustrative example. DESIGN: The study involved a general practice morbidity survey, conducted over 12 months in 1981-82. All patients who consulted their general practitioners with a diagnosis of diabetes mellitus (type 1 or type 2) were identified and the number of these who consulted with additional morbidities were counted for each rubric of the Royal College of General Practitioners' modification of the International Classification of Disease. These observed numbers were then compared with expected numbers calculated from the total non-diabetic population after standardisation by age. Standardised person consulting ratios (SPCR) were derived and the 99% confidence intervals (CI) surrounding these values calculated. SETTING: This was a national survey involving the whole of England and Wales. PATIENTS: The study involved 280,000 patients from selected general practices, of whom 953 males and 1035 females consulted their general practitioners with diabetes. MEASUREMENTS AND MAIN RESULTS: In an examination of 80 disease rubrics in the diabetic population in which there were at least 20 observed or expected cases, there were 34 among males and 28 among females in which there were increased values of the SPCR, and none in which the SPCR was decreased. SPCRs were high for infections generally (bacterial, fungal, and viral) and particularly so for cardiovascular disorders and for hypothyroidism in males. Though SPCRs for upper respiratory infections were increased, those for asthma and hay fever were not. SPCRs for neoplasms as a group were not raised. CONCLUSION: By confirming other work and widely held clinical opinion, this study has shown the potential of this data base for the examination of disease concurrence.

The problem of diagnostic variability in general practice.

STUDY OBJECTIVE: The aim was to examine the scale, source, and relevance of variation between general practices in respect of the rates with which patients consulted with illnesses falling in each of several diagnostic groups. DESIGN: This study involved a general practice morbidity survey conducted over two years, 1970-72. All patients who consulted their general practitioners were identified and the number of these who consulted with diagnoses attributable to each of the 18 main chapters of the International classification of diseases were counted. Patients who consulted for more than one diagnosis within a chapter were counted once only; those who consulted for one or more diagnoses in each of several chapters were counted once for each chapter. SETTING: This was a national survey involving general practitioners in England and Wales. SUBJECTS: The study involved 214,524 patients from 53 selected general practices (115 doctors) who were registered with their general practitioners for the whole of the year 1970-71 and for whom their morbidity data had been linked with their social data from the 1971 census. MEASUREMENTS AND MAIN RESULTS: Using the numbers of patients on the practice lists as denominators, practice patient consulting rates (PPCR) were calculated for each practice and for each ICD chapter. Variability in chapter PPCR was examined by calculating coefficients of variation and, after allowance for random variation, coefficients of residual variation. There were large interpractice (doctor) variations in all chapter rates. These variations were only marginally attributable to: chance; different age, sex and social class mixes of practice populations; geographical locations; and practice organisation. The rates were, however, consistent from one year to the next for any one practice. Approximately half of the interpractice (doctor) diagnostic variability was associated with overall patient consulting behaviour. When the effects of this behaviour were discounted, any major residual diagnostic variability was confined largely to ICD chapters I-V, XVI, and XVII, ie, those chapters where aetiology forms the basis of classification. CONCLUSION: Variations in recorded diagnostic rates are mainly due to the consistent but idiosyncratic and selective exclusion by practitioners of some components from the total set which often coexist in a new diagnosis. Because of the scale of interpractice diagnostic variability, the use of algorithms and information technology is largely precluded from outcome studies, auditing procedures, and studies of practice work loads in general. However, (1) the consistency of any individual doctor's pattern of diagnostic recording from one year to another permits studies of trends; and (2) given a reasonable number of recording practices, the population mean practice consulting rates can be estimated with sufficient accuracy for many epidemiological research and administrative uses.

Concurrence of monthly variations of mortality related to underlying cause in Europe.

STUDY OBJECTIVE: The study aimed to examine the concurrence in the variation of monthly numbers of deaths in summer and winter from the four main underlying causes - respiratory, circulatory, neoplastic, and all others - in four countries. In particular, the hypothesis that most non-respiratory concurrent deaths are miscoded respiratory deaths and that a large proportion of the winter mortality currently attributed to circulatory disorders should be attributed to respiratory causes was considered. DESIGN: Mortality data were analysed graphically in relation to cause. Each of the four series of monthly data underwent time series analysis to remove auto-correlation, seasonality, and secular trends. Associations between paired causes of death and between multiple series (using Kendall's coefficient of concordance) were then examined after modelling. SETTING: Monthly deaths (65 years and over) related to underlying cause were examined for England and Wales (nine years), The Netherlands (nine years), Denmark (10 years), and Portugal (10 years - all ages). Weekly data for England and Wales (51 weeks) were also analysed. MAIN RESULTS: All combinations of monthly deaths related to underlying cause were strongly associated in all four countries. This concurrence was evident down to the lowest monthly values so that all seasonally related deaths above the minimum monthly value can be used as an estimate of the "concurrent" proportion. Associations involving deaths from neoplasm were weakest. Concurrence was evident even on a weekly analysis (England and Wales). Concurrent deaths in England and Wales accounted for 31.1% of respiratory, 16.0% of circulatory, 3.5% of neoplastic, 14.1% of deaths from other causes and 14.2% for all deaths combined. The equivalent percentages for concurrent deaths from all causes were 8.4% in the Netherlands, 9.3% in Denmark, and 16.8% in Portugal. CONCLUSIONS: Concurrence, which was present in each of the underlying causal groups in each of the four national data sets examined, suggests a common cause separate from the underlying cause that has been used in the presentation of mortality statistics. If the person concerned had not died at that time, as a result of this cause, he would not have died from the recorded underlying cause. Most of these non-respiratory concurrent deaths are miscoded. As a consequence, a large proportion of winter mortality currently attributed to circulatory disorders should be attributed to other causes, probably respiratory. More intensive research into the contribution made by acute respiratory diseases is proposed. The proportion of concurrent deaths varied in the four countries thereby limiting the validity of simple comparisons of national mortality statistics.

Patients consulting with Crohn's disease in primary care in England and Wales.

OBJECTIVE: To determine annual incidence and prevalence for patients consulting their GP because of Crohn's disease in England and Wales and compare demographic details with matched controls. DESIGN: We used the fourth Morbidity Statistics in General Practice study (MSGP-4) which covered 468 042 person-years during a 12-month period in 1991-92. METHODS: All GPs reporting a patient with Crohn's disease in MSGP-4 were sent a questionnaire to confirm the diagnosis and obtain supportive details (surgical, pathological, radiological and/or endoscopic). Data concerning ethnicity, social class, smoking status, living in an urban or rural environment and employment had been collected previously. Conditional logistic regression models were used to analyse the data for cases and matched controls. RESULTS: Three hundred and fifteen patients were reported to have Crohn's disease. Replies were obtained to 251 (80%) questionnaires. The diagnosis of Crohn's disease was confirmed in 184 cases (89%) and refuted in 23 cases (11%) -- details were unavailable for 44 patients. The mean age of patients was 44 years, the female:male ratio was 1.46:1, and 108 (59%) patients had required surgery. Thirty-three of 178 (18.5%) patients were diagnosed within the study period. Hence, this study detected a prevalence for consulting Crohn's disease of 54.6-59.8/100,000 and an annual incidence of 10.1-11.1/100,000 in 1991-92. No significant differences were found between cases (n = 291) and controls (n = 1682) with regard to ethnicity, social class, smoking or living in an urban/rural environment. Patients with Crohn's disease had similar employment levels as controls, but were significantly more likely to be registered as permanently sick, odds ratio 4.01 (CI 2.21-7.29). CONCLUSIONS: This national survey, including 1% of the population, suggests there are approximately 30,600 patients consulting their GP because of Crohn's disease in England and Wales, with 5700 new cases diagnosed per year.

The impact of three influenza epidemics on primary care in England and Wales.

The numbers of persons with influenza presenting to general practitioners in England and Wales during the epidemics of late 1989, late 1993, and early 1995 are estimated to be approximately 760,00, 480,000 and 192,000, respectively. The expected numbers used to derive these estimates were obtained by averaging incidence by week over the 9 winters of 1986/87 to 1994/95, excluding those weeks in which influenza was prevalent. These 3 epidemics varied in magnitude and in the relative impact on persons in different age groups. The influenza B epidemic in 1995 scarcely affected elderly people. During the 3 epidemic periods, increased numbers of persons consulted their general practitioners with other respiratory diseases, including pneumonia, acute bronchitis and otitis media. The patterns of increase were not consistent between the epidemics, partly because of the differing impact on the various age groups and partly because of the effect of other respiratory viral illnesses prevalent at the same time. No increase occurred in the numbers of persons reported with new episodes of cerebrovascular accident or of acute myocardial infarction. A similar method was used to estimate excess deaths, which amounted to 25,000 in 1989, 13,000 in 1993, and 500 in 1995. In the periods immediately following the influenza epidemics, the observed pattern of deaths conformed to the expected, demonstrating that persons dying during the epidemics were not just dying a few weeks prematurely.

Cost-effectiveness analysis of inhaled zanamivir in the treatment of influenza A and B in high-risk patients.

OBJECTIVE: To evaluate the cost effectiveness of zanamivir 10 mg twice daily for 5 days in the treatment of influenza in high-risk patients. DESIGN: Bootstrap cost-effectiveness analysis incorporating within-trial analysis of pooled patient-level cost and effect data. SETTING: UK unit costs and utilities applied to high-risk patients drawn from 6 multinational clinical trials. PATIENTS: A total of 154 zanamivir and 167 placebo high-risk patients were included in the analysis. MAIN OUTCOME MEASURES: Cost per day of normal activities; cost per symptom-free day; cost per complication averted; cost per quality-adjusted life-year (QALY). RESULTS: The mean benefit was estimated to be 2.5 days [95% confidence interval (CI): 0.68 to 4.27] of normal activities gained; 2.0 (95% CI: 0.56 to 3.51) symptom-free days; and a 9% reduction in complications (95% CI: 0 to 18%). Excluding the effect of rare hospitalisation costs, the cost (1999 values) of gaining a day of normal activities was 9.50 Pounds (95% CI: 5 Pounds to 39 Pounds); cost per symptom-free day was 11.56 Pounds (95% CI: 6 Pounds to 43 Pounds); cost per complication averted was 262 Pounds (95% CI: 90 Pounds to 1574 Pounds). Influenza was estimated to reduce utility by 0.883 per day, demonstrating the debilitating effect of the disease. Extrapolating a day of normal activities to a standard utility measure resulted in a cost per QALY of 3900 Pounds excluding inpatient costs (7490 Pounds including inpatient costs). Cost-effectiveness acceptability curves demonstrated 90% certainty that zanamivir would be cost effective at 8000 Pounds per QALY. CONCLUSIONS: Significant health benefits can be obtained with zanamivir treatment in high-risk patients. The cost per QALY for zanamivir in these patients compares well with that of other commonly used pharmacological interventions.

Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Zanamivir Study Group.

OBJECTIVE: This study examined the impact of zanamivir treatment on patient morbidity in patients with influenza. DESIGN AND SETTING: This was a multicentre, randomised, double-blind, parallel-group study conducted in 14 countries in Europe and North America during the winter of 1995/1996. PATIENTS AND PARTICIPANTS: The study included 722 individuals with virologically confirmed influenza. INTERVENTIONS: Two different zanamivir treatment regimens [twice daily (bid) or 4 times daily (qid) for 5 days] were compared with placebo. MAIN OUTCOME MEASURES AND RESULTS: Efficacy was measured using a number of patient-assessment questionnaires. Results showed that significantly fewer patients with influenza who were treated with zanamivir had additional contacts with healthcare professionals compared with those who received placebo (8 vs 14%; p < or = 0.049, bid and qid vs placebo). Individuals treated with zanamivir also spent fewer days absent from work (placebo: mean = 3.28 days; qid: mean = 2.52 days; p = 0.031) or college/school (placebo: mean = 2.90 days; bid: mean = 2.24 days; p = 0.032), and showed significant improvements in productivity compared with placebo. The health status questionnaire revealed significant improvements in patient well-being over the first 5 days of the study in those treated with zanamivir compared with those who received placebo. CONCLUSIONS: Zanamivir treatment reduced absenteeism, improved patient productivity and well-being, and reduced the additional use of healthcare resources in patients with influenza.

Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study.

OBJECTIVES: To assess the clinical efficacy and safety of orally inhaled zanamivir in the treatment of influenza in a European primary care setting. METHODS: This was a randomized, double-blind, placebo-controlled trial in primary care and hospital clinics in 11 European countries. Patients aged > or = 12 years were recruited within 2 days of onset of typical influenza symptoms and received orally inhaled zanamivir 10 mg via a Diskhaler twice daily for 5 days or matching placebo. Influenza symptoms and temperature were recorded daily for 14 days. The primary endpoint was time to alleviation of clinically significant symptoms of influenza. Other endpoints included symptom severity, use of relief medications, time to return to normal activities, complications and investigator's assessment of symptoms. RESULTS: A total of 356 patients were recruited; 277 (78%) had laboratory-confirmed influenza and 32 (9%) were considered high-risk (i.e. elderly or with underlying medical conditions). Zanamivir significantly reduced the time to alleviation of symptoms versus placebo (median 5 days versus 7.5 days, P<0.001), a 33% reduction in duration of illness. Zanamivir significantly reduced the severity of several symptoms; improvements versus placebo were discernible after approximately 24 h. The proportion of patients who were afebrile after 24 h increased by 46% versus placebo. Similar treatment benefits were observed in the high-risk patients. Zanamivir was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSIONS: Zanamivir is effective in reducing the duration and severity of influenza illness and is well tolerated. Zanamivir should therefore be a clinically valuable intervention in the management of influenza.