Vaccines for preventing influenza in people with asthma.

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusion was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the efficacy of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. The last search was carried out in September 2007. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were initially included. Four of these trials were of high quality. Six further articles have been included in three updates (Bueving 2003; Castro 2001; Fleming 2006; Redding 2002; Reid 1998). The included studies covered a wide diversity of people, settings and types of influenza vaccination, but data from the more recent studies that used similar vaccines have been pooled. BENEFITS: Bueving 2003 studied 696 children with asthma and did not demonstrate a significant reduction in influenza related asthma exacerbations (Risk Difference 0.01; 95% confidence interval -0.02 to 0.04). HARMS: The pooled results of two trials involving 2306 people with asthma did not demonstrate a significant increase in asthma exacerbations in the two weeks following influenza vaccination (Risk Difference 0.00; 95% confidence interval -0.02 to 0.02). AUTHORS' CONCLUSIONS: Uncertainty remains about the degree of protection vaccination affords against asthma exacerbations that are related to influenza infection. Evidence from recently published trials indicates that there is no significant increase in asthma exacerbations immediately after vaccination (at least with inactivated influenza vaccination). There is concern regarding possible increased wheezing and hospital admissions in infants given live intranasal vaccination.

WITHDRAWN: Antivirals for the common cold.

BACKGROUND: The common cold is a ubiquitous short and usually mild illness for which preventive and treatment interventions have been under development since the mid-40s. As our understanding of the disease has increased, more experimental antivirals have been developed. This review attempts to draw together experimental evidence of the effects of these compounds. OBJECTIVES: To identify, assemble, evaluate and (if possible) synthesise the results of published and unpublished randomised controlled trials of the effects of antivirals to prevent or minimise the impact of the common cold. SEARCH STRATEGY: We searched electronic databases, corresponded with researchers and handsearched the archives of the MRC's Common Cold Unit (CCU). SELECTION CRITERIA: We included original reports of randomised and quasi-randomised trials assessing the effects of antivirals on volunteers artificially infected and in individuals exposed to colds in the community. DATA COLLECTION AND ANALYSIS: We included 241 studies assessing the effects of Interferons, interferon-inducers and other antivirals on experimental and naturally occurring common colds, contained in 230 reports. We structured our comparisons by experimental or community setting. MAIN RESULTS: Although intranasal interferons have high preventive efficacy against experimental colds (protective efficacy 46%, 37% to 54%) and to a lesser extent against natural colds (protective efficacy 24%, 21% to 27%) and are also significantly more effective than placebo in attenuating the course of experimental colds (WMD 15.90, 13.42 to 18.38), their safety profile makes compliance with their use difficult. For example, prolonged prevention of community colds with interferons causes blood-tinged nasal discharge (OR 4.52, 3.78 to 5.41). Dipyridamole (protective efficacy against natural colds 49%, 30% to 62%), ICI 130, 685 (protective efficacy against experimental colds 58%, 35% to 74% ), Impulsin (palmitate) (protective efficacy against natural colds 44%, CI 35% to 52% ) and Pleconaril (protective efficacy against experimental colds 71%, 15% to 90% ) appear to have important antiviral properties and are well-tolerated. The evidence of effectiveness of other compounds in the treatment of experimental or natural colds is sparse. AUTHORS' CONCLUSIONS: There are no licensed effective antivirals for the common cold. Because prolonged intranasal administration causes a clinical picture which is not distinguishable from the common cold, interferons have no place in everyday use. Further assessment of the effects of dipyridamole, ICI 130, 685, Impulsin (palmitate) and Pleconaril in preventing the common cold should be carried out. Given the multi-agent nature of the causes of the common cold, future research efforts should focus on non virus-specific compounds.

Vaccines for preventing influenza in healthy adults.

BACKGROUND: Different types of influenza vaccines are currently produced world-wide. Healthy adults are at present targeted only in North America. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has a negative impact on their acceptance and uptake. OBJECTIVES: To identify, retrieve and assess all studies evaluating the effects (efficacy, effectiveness and harms) of vaccines against influenza in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2005) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to January 2006); and EMBASE (1990 to January 2006). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, no intervention. Live, attenuated, or killed vaccines or fractions of them administered by any route, irrespective of antigenic configuration were assessed. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 16 to 65 years were considered. Comparative non-randomised studies were included if they assessed evidence of the possible association between influenza vaccines and serious harms. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Forty-eight reports were included: 38 (57 sub-studies) were clinical trials providing data about effectiveness, efficacy and harms of influenza vaccines and involved 66,248 people; 8 were comparative non-randomised studies and tested the association of the vaccines with serious harms; 2 were reports of harms which could not be introduced in the data analysis. Inactivated parenteral vaccines were 30% effective (95% CI 17% to 41%) against influenza-like illness, and 80% (95% CI 56% to 91%) efficacious against influenza when the vaccine matched the circulating strain and circulation was high, but decreased to 50% (95% CI 27% to 65%) when it did not. Excluding the studies of the 1968 to 1969 pandemic, effectiveness was 15% (95% CI 9% to 22%) and efficacy was 73% (95% CI 53% to 84%). Vaccination had a modest effect on time off work, but there was insufficient evidence to draw conclusions on hospital admissions or complication rates. Inactivated vaccines caused local tenderness and soreness and erythema. Spray vaccines had more modest performance. Monovalent whole-virion vaccines matching circulating viruses had high efficacy (VE 93%, 95% CI 69% to 98%) and effectiveness (VE 66%, 95% CI 51% to 77%) against the 1968 to 1969 pandemic. AUTHORS' CONCLUSIONS: Influenza vaccines are effective in reducing cases of influenza, especially when the content predicts accurately circulating types and circulation is high. However, they are less effective in reducing cases of influenza-like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications. Whole-virion monovalent vaccines may perform best in a pandemic.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults.

BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in interpandemic years and in a pandemic. OBJECTIVES: To assess the effects of NIs in preventing or ameliorating influenza, its transmission and its complications in healthy adults and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2004 to September, Week 4 2005), EMBASE (2003 to June 2005) and contacted manufacturers, researchers in the field, and authors of studies evaluated in the review. SELECTION CRITERIA: Randomised or quasi-randomised placebo-controlled studies of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two authors applied inclusion criteria, assessed trial quality and extracted data. We structured the comparisons into prophylaxis, treatment and adverse events with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza. AUTHORS' CONCLUSIONS: Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.

Influenza vaccination for health-care workers who work with elderly people in institutions: a systematic review.

Our aim was to review the evidence of efficacy and effectiveness of influenza vaccination of health-care workers in reducing cases of influenza-like illness, influenza, complications from influenza, death from influenza, and death from all causes among the elderly people they care for in institutions. We searched 11 electronic databases in any language and identified two cluster-randomised controlled trials with moderate risk of bias and one cohort study at high risk of bias that addressed our questions. Staff vaccination had a significant effect on influenza-like illness (vaccine effectiveness [VE] 86%, 95% CI 40-97%) only when patients were vaccinated too. If patients were not vaccinated, staff immunisation had no effect. Vaccinating health-care workers did not appear efficacious against influenza (RR 0.87, 95% CI 0.46-1.63). There was no significant effect of vaccination on lower respiratory tract infections: (RR 0.70, 95% CI 0.41-1.20). Deaths from pneumonia were significantly reduced (VE 39%, 95% CI 2-62%), as were deaths from all causes (VE 40%, 95% CI 27-50%). These findings must be interpreted in the light of possible selection, performance, attrition, and detection biases.

Vaccines for preventing influenza in healthy adults.

BACKGROUND: Three different types of influenza vaccines are currently produced worldwide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. OBJECTIVES: To assess the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Twenty five reports of studies involving 59,566 people were included. The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness against clinical influenza cases: 15%(95% CI 8% to 21%) and 25% (95% CI 13% to 35%) respectively. Overall the percentage of participants experiencing clinical influenza decreased by 6%. Use of the vaccine significantly reduced time off work but only by 0.16 days for each influenza episode (95% CI 0.04 to 0.29 days); Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWERS' CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed cases of influenza. However, they are not as effective in reducing cases of clinical influenza and number of working days lost. Universal immunisation of healthy adults is not supported by the results of this review.

Vaccines for preventing influenza in people with asthma.

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusion was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the efficacy of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. The last search was carried out in February 2003. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were initially included. Four of these trials were of high quality. Five further articles have been included in two updates (Bueving 2002; Castro 2001; Redding 2002; Reid 1998). The included studies covered a wide diversity of people, settings and types of influenza vaccination, but data from the more recent studies that used similar vaccines have been pooled. The pooled results of two trials involving 2306 people with asthma did not demonstrate a significant increase in asthma exacerbations in the two weeks following influenza vaccination (Risk Difference 0.00; 95% confidence interval -0.02 to 0.02). A recent study on 696 children with asthma did not demonstrate a significant reduction in influenza related asthma exacerbations (Risk Difference 0.01; 95% confidence interval -0.02 to 0.04). REVIEWERS' CONCLUSIONS: Evidence from recently published trials indicates that there is no significant increase in asthma exacerbations immediately after vaccination (at least with inactivated influenza vaccination); however, uncertainty remains about the degree of protection vaccination affords against asthma exacerbations that are related to influenza infection.

Amantadine and rimantadine for preventing and treating influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects. MAIN RESULTS: Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%). Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWER'S CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. [This abstract has been prepared centrally.]

Antivirals for the common cold.

BACKGROUND: The common cold is a ubiquitous short and usually mild illness for which preventive and treatment interventions have been under development since the mid-40s. As our understanding of the disease has increased, more experimental antivirals have been developed. This review attempts to draw together experimental evidence of the effects of these compounds. OBJECTIVES: To identify, assemble, evaluate and (if possible) synthesise the results of published and unpublished randomised controlled trials of the effects of antivirals to prevent or minimise the impact of the common cold. SEARCH STRATEGY: We searched electronic databases, corresponded with researchers and handsearched the archives of the MRC's Common Cold Unit (CCU). SELECTION CRITERIA: We included original reports of randomised and quasi-randomised trials assessing the effects of antivirals on volunteers artificially infected and in individuals exposed to colds in the community. DATA COLLECTION AND ANALYSIS: We included 241 studies assessing the effects of Interferons, interferon-inducers and other antivirals on experimental and naturally occurring common colds, contained in 230 reports. We structured our comparisons by experimental or community setting. MAIN RESULTS: Although intranasal interferons have high preventive efficacy against experimental colds (protective efficacy 46%, 37% to 54%) and to a lesser extent against natural colds (protective efficacy 24%, 21% to 27%) and are also significantly more effective than placebo in attenuating the course of experimental colds (WMD 15.90, 13.42 to 18.38), their safety profile makes compliance with their use difficult. For example, prolonged prevention of community colds with interferons causes blood-tinged nasal discharge (OR 4.52, 3.78 to 5.41). Dipyridamole (protective efficacy against natural colds 49%, 30% to 62%), ICI 130, 685 (protective efficacy against experimental colds 58%, 35% to 74% ), Impulsin (palmitate) (protective efficacy against natural colds 44%, CI 35% to 52% ) and Pleconaril (protective efficacy against experimental colds 71%, 15% to 90% ) appear to have important antiviral properties and are well-tolerated. The evidence of effectiveness of other compounds in the treatment of experimental or natural colds is sparse. REVIEWER'S CONCLUSIONS: There are no licensed effective antivirals for the common cold. Because prolonged intranasal administration causes a clinical picture which is not distinguishable from the common cold, interferons have no place in everyday use. Further assessment of the effects of dipyridamole, palmitate, ICI 130, 685, Impulsin and Pleconaril in preventing the common cold should be carried out. Given the multi-agent nature of the causes of the common cold, future research efforts should focus on non virus-specific compounds.

Vaccines for preventing influenza in healthy adults.

BACKGROUND: Three different types of influenza vaccines are currently produced world wide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. OBJECTIVES: To identify, retrieve and assess all studies evaluating the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. SEARCH STRATEGY: MEDLINE was searched using the strategy of the Cochrane Acute Respiratory Infections Group. The bibliography of retrieved articles, the Cochrane Controlled Trials Register (CCTR), and EMBASE (1990 to 1997) were also searched. Handsearch of the journal Vaccine from its first issue to the end of 1997 (Jefferson and Jefferson, 1996; Jefferson, 1998). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. DATA COLLECTION AND ANALYSIS: Both clinically defined cases and serologically confirmed cases of influenza were considered as outcomes according to the authors' definitions. Time off work, complication and hospitalisation rates were considered, together with adverse effects. Vaccine schedules were analysed including one component matching the recommended vaccine (WHO or government recommendations) for the year of the study, and whether they matched the circulating viral subtypes. MAIN RESULTS: The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza A by 48% (95% confidence interval 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 68% (95% confidence interval 49% to 79%). The vaccines were less effective in reducing clinical influenza cases, with efficacies of 13% and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days for each influenza episode (95% confidence interval 0.1 to 0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWER'S CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed cases of influenza A. However, they are not as effective in reducing cases of clinical influenza. The use of WHO recommended vaccines appears to enhance their effectiveness in practice.

Amantadine and rimantadine for preventing and treating influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects. MAIN RESULTS: Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%). Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system adverse and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWER'S CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine.

Vaccines for preventing influenza in people with asthma (Cochrane Review).

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusions was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the effects of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were included. Four of these trials were of high quality. One further article has been included since the previous version of this review. Inclusion of the new trial has not altered the conclusions of this review. The included studies covered a wide diversity of people, settings and types of influenza vaccination, so data from the different trials were not pooled. In one trial, no protective effect of influenza vaccination against asthma exacerbation was demonstrated, but the incidence of influenza was low during the study period. A higher number of asthma exacerbations following killed influenza vaccination was found in one trial (risk difference 3 1%, 95% confidence interval 0.3% to 5.8%). When people with upper respiratory tract infections were excluded, this difference was no longer significant. A small trial using recombinant vaccine found no significant difference in asthma exacerbations between the vaccinated and placebo groups. Updated search conducted July, 2000. No new trials were identified. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the benefits and risks of influenza vaccination for people with asthma.

Vaccines for preventing influenza in people with asthma.

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusions was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the effects of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were included. Four of these trials were of high quality. One further article has been included since the previous version of this review. Inclusion of the new trial has not altered the conclusions of this review. The included studies covered a wide diversity of people, settings and types of influenza vaccination, so data from the different trials were not pooled. In one trial, no protective effect of influenza vaccination against asthma exacerbation was demonstrated, but the incidence of influenza was low during the study period. A higher number of asthma exacerbations following killed influenza vaccination was found in one trial (risk difference 3 1%, 95% confidence interval 0.3% to 5.8%). When people with upper respiratory tract infections were excluded, this difference was no longer significant. A small trial using recombinant vaccine found no significant difference in asthma exacerbations between the vaccinated and placebo groups. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the benefits and risks of influenza vaccination for people with asthma.

Amantadine and rimantadine for preventing and treating influenza A in adults.

OBJECTIVES: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and concerns about possible adverse effects. The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects. MAIN RESULTS: Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%) Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system adverse and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWER'S CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine.

Vaccines for preventing influenza in healthy adults.

OBJECTIVES: To identify, retrieve and assess all studies evaluating the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. SEARCH STRATEGY: MEDLINE was searched using the strategy of the Cochrane Acute Respiratory Infections Group. The bibliography of retrieved articles, the Cochrane Controlled Trials Register (CCTR), and EMBASE (1990 to 1997) were also searched. Handsearch of the journal Vaccine from its first issue to the end of 1997 (Jefferson and Jefferson, 1996; Jefferson, 1998). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. DATA COLLECTION AND ANALYSIS: Both clinically defined cases and serologically confirmed cases of influenza were considered as outcomes according to the authors' definitions. Time off work, complication and hospitalisation rates were considered, together with adverse effects. Vaccine schedules were analysed including one component matching the recommended vaccine (WHO or government recommendations) for the year of the study, and whether they matched the circulating viral subtypes. MAIN RESULTS: The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza A by 48% (95% confidence interval 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 68% (95% confidence interval 49% to 79%). The vaccines were less effective in reducing clinical influenza cases, with efficacies of 13% and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days for each influenza episode (95% confidence interval 0.1 to 0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWER'S CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed cases of influenza A. However, they are not as effective in reducing cases of clinical influenza. The use of WHO recommended vaccines appears to enhance their effectiveness in practice.

The development of a health policy for the Army.

This paper describes the development of the Army Health Policy (AHP), which is a key component of the Army Human Resources Strategy (AHRS). The work on the AHP provided an opportunity for a fundamental review of the delivery of health support to the Army. The AHP will provide the strategic framework by which the Army will ensure the health of its workforce and, where appropriate, their dependents. The methodology used for this work may be a useful model for the development of a health policy for occupational populations.

Assessing the potential cost effectiveness of pneumococcal vaccines in the US: methodological issues and current evidence.

Pneumococcal disease imposes a notable burden on society, particularly in the elderly and those at high risk of complications. Preventive strategies, especially vaccines, are possibly the best way to minimise such a burden. We report on the conduct and results of a preliminary exploratory review of the economics of pneumococcal vaccines in the elderly population in the US. After extensive electronic and manual searches, we identified 5 economic evaluations that fulfilled our study criteria. From these we extracted key economic variables and assessed the quality of the studies against the criteria in the checklist for authors and peer reviewers of economic submissions to the British Medical Journal. We found variation of quality of study design such as a lack of clarity in the treatment of indirect costs and a failure to present the data on resource use and costs separately. We carried out supplementary searches to assess the quality of the epidemiological and efficacy evidence upon which the economic models were based and found contradictory evidence of effects of the vaccines, which included the results of 2 meta-analyses. One of these meta-analyses reported that retrospective studies, especially case-control studies, tended to underestimate the protective efficacy of the vaccine by as much as 20%. We believe that a well resourced Cochrane review of the clinical evidence of the effects of the vaccines should be carried out before any further economic studies. No more economic modelling should take place before such a review is undertaken.

J95-EPINATO based planning parameters for medical support to Operations Other Than War (OOTW).

As with increasing frequency the armies of NATO member states deploy on Operations Other Than War (OOTW), there is a requirement to define predictory variables of consumption of healthcare assets by type and geographical location of operations. This report presents the results of the analysis of the J95/EPINATO database of operational and exercise deployments. Although the database is limited in size and scope results show a marked difference in rates of incidence of EVENTS and in the proportion of first attendances to working days lost, both in general and when analysed by deployment type. For instance Service Assisted or Protected Evacuations (SA/PE) showed a relatively high incidence of first attendances and low incidence of working days lost for all reasons (or EVENTS) (214.5 per 1,000 personnel at risk per month-95% Confidence Interval-CI: 198.8 to 230.3 and 23.9 working days lost per 1,000 personnel at risk per month-95% CI 18.0 to 29.8). The reverse is true for Counter Insurgency (COIN) type operations (111.55 per 1,000 personnel at risk per month-95% CI: 110.9 to 112.2 and 161.25 working days lost per 1,000 personnel at risk per month 95% CI: 160.5 to 162.0). Other findings include highest attendance rates in exercise deployments for all reasons (264.7 per 1,000 personnel per month 95% CI: 261.2 to 268.1), highest hospitalisation rates in exercise and PSO deployments for all reasons (8.7 per 1,000 personnel per month 95% CI: 7.9 to 9.4 and 9.9 per 1,000 personnel per month 95% CI: 9.6 to 10.1) and the seasonal pattern, high incidence and low manpower impact (26.2 per 1,000 personnel per month 95% CI: 25.9 to 26.5 and 3.5 per 1,000 personnel per month 95% CI: 3.4 to 3.6) of dermatological consultations on all operational deployments (the lowest of the spectrum being in COIN operations). No relationship was found between incidence of consultations, working days lost, hospitalisations and distance of the deployment from the UK. Deployments to Africa show the highest incident of attendances and working days lost for all reasons (530.7 per 1,000 personnel per month 95% CI: 524.2 to 537.3 and 106.5 per 1,000 personnel per month 95% CI: 102.5 to 110.6). The variability in epidemiological profiles in this analysis demonstrates the dangers of exclusive reliance on synthetic classifications of reasons for attendances such as the traditional DNBI breakdown and on point estimates of incidence. As the database expands, further analysis will become possible.

Morbidity surveillance in the British Army--the first 12 months.

This paper describes the data obtained during the first 12 months of the morbidity surveillance system used, world-wide, by the British Army in operational and non-operational settings and the economic impact of such morbidity in terms of estimated working days lost. Analysis is provided on primary health care and dental morbidity, the surveillance of patients undergoing physiotherapy and those Service personnel cared for by the NHS. The surveillance of the latter population shows a high burden of morbidity which, previously, has never been quantified. The most frequent cause of attendance within primary health care is injuries (all causes) with an annual total of 77,254--a rate per 1,000 personnel per month of 51.92. This leads to an annual loss of manpower, in terms of estimated working days lost of 127,839--a rate per 1,000 personnel per month of 85.91. Army Training Regiments (ATRs-5 sites), Infantry Training Centres (ITCs-2 sites) and the Royal Military Academy Sandhurst (RMAS) are grouped together as Selected Training Establishments (STEs) and show attendance rates higher than the mean for all causes. Summary results of Cochrane systematic reviews presenting up-to-date concise information on experimental evidence as to which preventive interventions should be used to diminish the notable impact of injuries on Army personnel are also given.