Example of antimicrobial stewardship program in a community hospital in Italy.

BACKGROUND: Inappropriate use of antibiotics has caused the emergence of resistant strains of bacteria. The hospital of Alessandria, Italy, implemented an antimicrobial stewardship (AS) pilot program between 2013 and 2015 in the intensive care units (ICUs) and internal medicine departments of Casale Monferrato and Tortona. We aimed to describe the project, results at the end of the intervention, and its strengths and weaknesses. METHODS: The protocol, designed by the local infection control committee, included three consecutive steps: local guidelines for empirical antibiotic therapy and list of prescription antibiotics with justification, monitoring of antibiotic consumption and antimicrobial resistance trend, and peer-to-peer audit sessions in the wards. RESULTS: One thousand and eighty-five observations were made, corresponding to 850 patients admitted to the ICUs (16.7%) and internal medicine departments (83.3%). Appropriate antibiotic prescriptions increased by 6.4% between 2013 and 2015. The greatest improvement in appropriate prescriptions was observed for glycopeptides and fluoroquinolones (+17.4% and +16.2%, respectively). We reported 305 inappropriate prescriptions, with the most frequent errors being absence of an infectious process (33.3%), inadequate combination therapy (12.8%), and absence of microbiological investigations (8.5%). A reduced incidence of methicillin-resistant Staphylococcusaureus (MRSA) was also observed (p<0.0037). CONCLUSIONS: Antimicrobial stewardship programs contribute to improving antibiotic prescription and can be implemented in small community hospitals. Narrower interventions, focused on a single disease or single antibiotic should be encouraged.

The importance of negative predictive value (NPV) of vulnerable elderly survey (VES 13) as a pre-screening test in older patients with cancer.

The importance of prognostic value of the comprehensive geriatric assessment (CGA) is well known in geriatric oncology, but there is no consensus on the use of alternative abbreviated screening methods for the evaluation of older patient disabilities. The participants in this study underwent vulnerable elderly survey 13 (VES 13) at first entry in Oncology Department and were later assessed by a geriatrician according to CGA. A score >3 for VES 13 identified patients as vulnerable. Aim of this study was to evaluate the specificity, sensibility, positive predictive value (PPV), and negative predictive value (NPV) of VES 13 versus cumulative illness rating scale (CIRS), activities of daily living (ADL), instrumental activities of daily living (IADL), and short portable mental status questionnaire (SPMSQ). Hundred and seventeen patients (mean age 78.8 years) entered the study. The NPV of VES was 74.6% for CIRS, 90.1% for IADL, 93.0% for ADL, and 100% for SPMSQ. As for PPV, the VES 13 showed no accuracy. We can conclude that VES 13 demonstrated sufficient accuracy as a screening test in identifying elderly "fit" patients in order to spare the more time-consuming CGA.

Migraineurs show a high prevalence of antiphospholipid antibodies.

BACKGROUND: It has been observed that migraineurs show a higher risk of thrombosis and that the most frequent symptom reported by patients with antiphospholipid syndrome is headache, especially migraine. OBJECTIVES: The aim of our research was to evaluate the prevalence of antiphospholipid antibodies (aPL) in a random cohort of migraineurs. PATIENTS/METHODS: This analytic, comparative case study was performed to evaluate the prevalence of antiphospholipid antibodies by comparing a population of migraineurs with and without aura with sex- and age-matched controls. Both the diagnosis of migraine and the laboratory diagnosis of aPL positivity were made on the basis of the most recent international guidelines. RESULTS: Between September 2008 and August 2009, we recruited 284 consecutive patients (225 women and 59 men, 203 without aura and 81 with aura) and 225 controls (174 women and 51 men). Positivity for at least one test for aPL (LAC, ACA IgG or antiß2GLP1 IgG) was detected and confirmed in 12% (n = 33) of patients and in 3% (n = 7) of controls (odds ratio, 4.08; confidence interval, 1.77-9:39; P = 0.0004). Two of the patients had triple positivity for aPL (LAC, ACA and antiß2GLP1) and one had double positivity (LAC and antiß2GLP1); none of the controls showed multiple positivity. CONCLUSIONS: Our data show that migraineurs have a significantly higher prevalence of antiphospholipid antibodies, and point towards the fact that the two conditions may be comorbid or even that migraine may be an early sign for identifying patients with aPL positivity.

Anatomical variants of the circle of willis and brain lesions in migraineurs.

BACKGROUND: Some reports demonstrated vascular alterations in brain magnetic resonance imaging (MRI) in migraineurs and a relationship between circle of Willis (Circle) variants and lacunar brain infarcts. We examined anomalies of the whole circle of Willis and their relationship with vascular brain lesions in migraineurs, to identify any possible vascular mechanism in migraine. METHODS: We studied, with a cohort controlled study, the circle of Willis in migraineurs seen consecutively in our Headache Center, and in non-headache controls, using angio-MRI of the brain. Statistical analysis used ANOVA, Scheffè's criterion, t-student test. RESULTS: We recruited 270 migraineurs (204 without aura (MWOA), 66 with aura (MWA) and 159 controls. Migraineurs presented an anatomical variant in 108 (40%) cases with 34 controls (21.4%) presenting a variant. We found a significant association between MWOA and variants (OR=2.4 CI95% [1.5 to 3.9]) and between MWA and variants (OR=3.2 CI95% [1.6 to 4.1]). Unilateral posterior variants with basilar hypoplasia are statistically associated only with MWA compared to controls (OR=9.2, CI95% [2.3 to 37.2]). Thirty-three percent of MWOA and 24% of MWA sufferers present some kind of brain lesion, included 2% of infra-tentorial lesions. We did not find any statistical association between the presence of Circle variants and ischemic lesions on MRI (OR=1.5 CI95% [0.68; 1.94]), or with infratentorial lacunar lesions (OR=1.58 CI95% [0.48 to 5.24]). CONCLUSIONS: Anatomical variants of the Circle of Willis are significantly more frequent in migraineurs; posterior anomalies are more frequent in MWA, suggesting a vascular mechanism provoking changes in cerebral blood flow, thereby stimulating cortical spreading depression.

The Piemonte Regional Allergy Network: a model of healthcare organization.

The Allergology Hospital Network and Regional Register for Severe Allergic Reactions (Regional Observatory) is the Piemonte Health Authority new challenge. It satisfied the need to promote and monitor the best practice among a variegated pool of specialists and to define both state of the art and evolution of efficiency and efficacy of standard working process. Harmonization in clinical daily activities and report of severe allergic reactions notified to Regional Observatory, had been gained by mean of a customized Information Technology (IT) solution. The overall target is to ensure a correct diagnostic treatment to patients with severe allergic reactions preventing possible future reactions. Statistics data as a whole, provide basilar epidemiological information to allocate both economical and human resources and to fulfill the rising of health diseases. Piemonte Allergology Medical Network with the Regional Register are an Italian unique and innovative project. It would represent a benchmark for other medical branches.

Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review.

OBJECTIVE: To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines. DESIGN: Systematic review without meta-analysis. DATA EXTRACTION: Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out. DATA SYNTHESIS: We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were less likely to have conclusions favouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences between means 5.04). Study size was not associated with concordance, content of take home message, funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding. CONCLUSION: Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size.

Suspected acute allergic reactions: analysis of admissions to the Emergency Department of the AOU Maggiore della Carità Hospital in Novara from 2003 to 2007.

OBJECTIVE OF THE STUDY: The aim of our work is to ascertain the frequency and the impact of acute allergic reactions on the routine of a highly-specialized Emergency Department collecting information on the admission, the typology of symptoms and the degree of severity calculating the incidence and the outcomes of the events. MATERIALS AND METHODS: The study started the 1 July 2006 and the records of the Emergency Department of the Maggiore della Carità Hospital in Novara were consulted retrospectively in the period between the 1 January 2003 and the 31 December 2006, and prospectively up to the 31 December 2007, using keywords that could identify admission for suspected allergic reactions. Information relating to internal medicine and/or pediatric cases were examined, excluding all surgical and/or trauma cases. The number ofadmissions per year was considered broken down by clinical signs, triage assessment upon admission and discharge outcome. RESULTS: Admissions to the Emergency Department during the period under consideration were 165,120 with 6107 suspected cases of allergic reactions. The symptoms most frequently reported both in adults (A) and children (C < or =18 years old), were: hives 37%, asthma 20.65 (A)% and 27.4% (C); drug allergy 7.5% (A) and 6.1% (C). Reactions to Hymenoptera venom were less frequent, 4.7% (A) and 1.27% (C); the frequency of angioedema, conjunctivitis and rhinitis was between 1 and 4%. The incidence of food allergies (1.4%) and anaphylaxis (0.8%) was comparable for all ages. The triage assessment showed a significant percentage of "yellow" and "red" codes, with 362 cases (5.9%) and 71 cases (1.16%) respectively. A total of 151 patients was hospitalized, no one classified as "white" code. Death occurred in 7 cases: 4 "yellow" codes and 3 "red" codes, respectively. A more detailed specialistic evaluation was recommended in only 10% of the patients. CONCLUSIONS: Admissions to the Emergency Department for suspected allergic reaction are proportional to the number of overall admissions for internal medicine cases and do not appear to be related to the general increase of allergies in the population. This led us to focus our attention on how allergic diseases impact the work of an Emergency Department and how to describe the discharge diagnosis better. A significant number of descriptive diagnoses also turned out to be inaccurate and did not allow the syndrome to be identified properly. The analysis of this information aims to be a stimulus to improve the emergency clinical approach used for allergic diseases and to plan the adequate management ofallergic patients after they have been treated in hospital.

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.

Peer review for improving the quality of grant applications.

BACKGROUND: Grant giving relies heavily on peer review for the assessment of the quality of proposals but the evidence of effects of these procedures is scarce. OBJECTIVES: To estimate the effect of grant giving peer review processes on importance, relevance, usefulness, soundness of methods, soundness of ethics, completeness and accuracy of funded research. SEARCH STRATEGY: Electronic database searches and citation searches; researchers in the field were contacted. SELECTION CRITERIA: Prospective or retrospective comparative studies with two or more comparison groups assessing different interventions or one intervention against doing nothing. Interventions may regard different ways of screening, assigning or masking submissions, different ways of eliciting opinions or different decision making procedures. Only original research proposals and quality outcome measures were considered. DATA COLLECTION AND ANALYSIS: Studies were read, classified and described according to their design and study question. No quantitative analysis was performed. MAIN RESULTS: Ten studies were included. Two studies assessed the effect of different ways of screening submissions, one study compared open versus blinded peer review and three studies assessed the effect of different decision making procedures. Four studies considered agreement of the results of peer review processes as the outcome measure. Screening procedures appear to have little effect on the result of the peer review process. Open peer reviewers behave differently from blinded ones. Studies on decision-making procedures gave conflicting results. Agreement among reviewers and between different ways of assigning proposals or eliciting opinions was usually high. AUTHORS' CONCLUSIONS: There is little empirical evidence on the effects of grant giving peer review. No studies assessing the impact of peer review on the quality of funded research are presently available. Experimental studies assessing the effects of grant giving peer review on importance, relevance, usefulness, soundness of methods, soundness of ethics, completeness and accuracy of funded research are urgently needed. Practices aimed to control and evaluate the potentially negative effects of peer review should be implemented meanwhile.

Dietary interventions for multiple sclerosis.

BACKGROUND: Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes. OBJECTIVES: We performed a Cochrane review of all randomised trials of dietary regimens for MS with the aim of answering MS consumers' questions regarding the efficacy and safety of these interventions. SEARCH STRATEGY: We searched the Cochrane MS Group trial register (February 2006), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 1, 2006, MEDLINE (PubMed) (1966 to March 2006), EMBASE (1974 to March 2006) and the bibliographies of papers found. SELECTION CRITERIA: All randomised controlled trials comparing a specific dietary intervention, diet plan or dietary supplementation, with no dietary modification or placebo, were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles, assessed trial quality and extracted data. Trial quality was poor, particularly as regards descriptions of randomisation, blinding and adverse event reporting. Some studies had large numbers of drop-outs; dropouts were never included in the analyses. MAIN RESULTS: PUFAs did not have a significant effect on disease progression, measured as worsening of Disability Status Scale. Omega-6 fatty acids (11-23 g/day linoleic acid) had no benefit in 75 relapsing remitting (RR) MS patients (progression at two years: relative risk (RR)=0.78, 95% CI [0.45 to 1.36]) or in 69 chronic progressive (CP) MS patients (RR=1.67, 95% CI [0.75 to 3.72]. Linoleic acid (2.9-3.4 g/day) had no benefit in CPMS (progression at two years: RR=0.78, 95% CI [0.43 to 1.42]). Slight decreases in relapse rate and relapse severity were associated with omega-6 fatty acids in some small studies, however these findings are limited by the limited validity of the endpoints.Omega-3 fatty acids had no benefit on progression at 12 months in 14 RRMS patients or at 24 months in 292 RRMS patients (RR=0.15, 95% CI [0.01 to 3.11], p= 0.22 at 12 months, and 0.82 95% CI [0.65 to 1.03], p=0.08, at 24 months). The low frequency of reported adverse events suggests no major toxicity associated with PUFA administration. No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria. AUTHORS' CONCLUSIONS: PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), and does not substantially affect the risk of clinical relapses over 2 years. However, the data available are insufficient to assess any potential benefit or harm from PUFA supplementation. Evidence bearing on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of diets interventions in MS.

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.

Vaccines for preventing influenza in the elderly.

BACKGROUND: Influenza vaccination of elderly individuals is recommended worldwide and has been targeted toward the elderly and those at serious risk of complications. OBJECTIVES: Our aim was to review the evidence of efficacy, effectiveness and safety of influenza vaccines in individuals aged 65 years or older. SEARCH STRATEGY: We searched the following databases on The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness (Issue 1, 2006); MEDLINE (January 1966 to March Week 3 2006); EMBASE (Dialog 1974 to 1979; SilverPlatter 1980 to December 2005); Biological Abstracts (SilverPlatter 1969 to December 2004); and Science Citation Index (Web of Science 1974 to December 2004). SELECTION CRITERIA: We considered randomised, quasi-randomised, cohort and case-control studies assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. Any influenza vaccine given independently, in any dose, preparation or time schedule, compared with placebo or with no intervention was considered. DATA COLLECTION AND ANALYSIS: We grouped reports first according to the setting of the study (community or long-term care facilities) and then by level of viral circulation and vaccine matching. We further stratified by co-administration of pneumococcal polysaccharide vaccine (PPV) and by different types of influenza vaccines. We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications and deaths. MAIN RESULTS: Sixty-four studies were included in the efficacy / effectiveness assessment, resulting in 96 data sets. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against ILI was 23% (6% to 36%) and non-significant against influenza (RR 1.04: 95% CI 0.43 to 2.51). We found no correlation between vaccine coverage and ILI attack rate. Well matched vaccines prevented pneumonia (VE 46%; 30% to 58%), hospital admission (VE 45%; 16% to 64%) and deaths from influenza or pneumonia (VE 42%, 17% to 59%). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19; 95% CI 0.02 to 2.01), ILI (RR 1.05: 95% CI 0.58 to 1.89), or pneumonia (RR 0.88; 95% CI 0.64 to 1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%; 12% to 38%) and all-cause mortality (VE 42%; 24% to 55%). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%; 21% to 33%), respiratory diseases (VE* 22%; 15% to 28%) and cardiac disease (VE* 24%; 18% to 30%); and for all-cause mortality (VE* 47%; 39% to 54%). The public health safety profiles of the vaccines appear to be acceptable. AUTHORS' CONCLUSIONS: In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest. The apparent high effectiveness of the vaccines in preventing death from all causes may reflect a baseline imbalance in health status and other systematic differences in the two groups of participants.

Amantadine and rimantadine for 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 efficacy, effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE (October 2003 to July 2005) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prophylaxis (prevention) trials the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.2). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prophylaxis 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. Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza. AUTHORS' CONCLUSIONS: Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. The effectiveness of both drugs in interrupting transmission is probably low. Routine use of both drugs should be discouraged and both drugs should only be used when all other measures fail.

Vaccines for preventing influenza in healthy children.

BACKGROUND: In children and adults the consequences of influenza are mainly absences from school and work, however the risk of complications is greatest in children and people over 65 years old. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with receiving influenza vaccines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); OLD MEDLINE (1966 to 1969); MEDLINE (1969 to December 2004); EMBASE (1974 to December 2004); Biological Abstracts (1969 to December 2004); and Science Citation Index (1974 to December 2004). We wrote to vaccine manufacturers and a number of corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years old. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Fifty-one studies involving 263,987 children were included. Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 79% (95% confidence interval (CI) 48% to 92%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two years compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Thirty-four reports containing safety outcomes were included, 22 including live vaccines, 8 inactivated vaccines and 4 both types. The most commonly presented short-term outcomes were temperature and local reactions. The variability in design of studies and presentation of data was such that meta-analysis of safety outcome data was not feasible. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in children older than two years but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. That no safety comparisons could be carried out emphasizes the need for standardisation of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given recent recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunisation in children is to be recommended as public-health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.

Antivirals for influenza in healthy adults: systematic review.

BACKGROUND: Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. METHODS: We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. FINDINGS: We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations (2.54, 1.50-4.31), and withdrawals because of adverse events (2.54, 1.60-4.06). There was no effect on asymptomatic cases (RR 0.85, 0.40-1.80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0.99 days, -1.26 to -0.71), but had no effect on nasal shedding of influenza A viruses (0.93, 0.71-1.21). The fewer data for rimantadine showed comparable effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1.79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza. INTERPRETATION: The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.

Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review.

BACKGROUND: Influenza vaccination of elderly individuals is recommended worldwide. Our aim was to review the evidence of efficacy and effectiveness of influenza vaccines in individuals aged 65 years or older. METHODS: We searched five electronic databases to December, 2004, in any language, for randomised (n=5), cohort (n=49), and case-control (n=10) studies, assessing efficacy against influenza (reduction in laboratory-confirmed cases) or effectiveness against influenza-like illness (reduction in symptomatic cases). We expressed vaccine efficacy or effectiveness as a proportion, using the formula VE=1-relative risk (RR) or VE*=1-odds ratio (OR). We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications, and deaths. FINDINGS: In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6-36) and non-significant against influenza (RR 1.04, 0.43-2.51). Well matched vaccines prevented pneumonia (VE 46%, 30-58) and hospital admission (VE 45%, 16-64) for and deaths from influenza or pneumonia (VE 42%, 17-59), and reduced all-cause mortality (VE 60%, 23-79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02-2.01), influenza-like illness (RR 1.05, 0.58-1.89), or pneumonia (RR 0.88, 0.64-1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12-38) and all-cause mortality (VE 42%, 24-55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21-33), respiratory diseases (VE* 22%, 15-28), and cardiac disease (VE* 24%, 18-30), and for all-cause mortality (VE* 47%, 39-54). INTERPRETATION: In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest.

Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review.

BACKGROUND: We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts, and Science Citation Index to June, 2004, in any language, and contacted vaccine manufacturers and authors of relevant studies to identify additional data. We included randomised, cohort, and case-control studies comparing efficacy of vaccines against influenza (reduction in laboratory-confirmed cases), effectiveness of vaccines against influenza-like illness (reduction in symptomatic cases), or both, with placebo or no intervention. We analysed the following outcomes: influenza, influenza-like illness, admissions, school absences, complications, and secondary transmission. FINDINGS: We included 14 randomised controlled trials, eight cohort studies, one case-control study, and one randomised controlled trial of intraepidemic use of the vaccines. Live attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children older than 2 years compared with placebo or no immunisation. Inactivated vaccines had lower efficacy (65%) than live attenuated vaccines, and in children aged 2 years or younger they had similar effects to placebo. Effectiveness of inactivated vaccines was about 28% in children older than 2 years. Vaccines were effective in reducing long school absences (relative risk 0.14 [95% CI 0.07-0.27]). Studies assessing the effects of vaccines against secondary cases, lower-respiratory tract disease, acute otitis media, and hospital stay suggested no difference with placebo or standard care, but lacked statistical power. INTERPRETATION: Influenza vaccines (especially two-dose live attenuated vaccines) are efficacious in children older than 2 years. Efficacy and effectiveness of the vaccines differed strikingly. Only two small studies assessed the effects of influenza vaccines on hospital admissions and no studies assessed reductions in mortality, serious complications, and community transmission of influenza. If influenza immunisation in children is to be recommended as public-health policy, large-scale studies assessing such important outcomes and undertaking direct comparisons of vaccines are urgently needed.