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Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
Cd005187 Standard
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  • 1. Influenza vaccination for healthcare workers who work with the elderly (Review) Thomas RE, Jefferson T, Demicheli V, Rivetti D This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 2 http://www.thecochranelibrary.com Influenza vaccination for healthcare workers who work with the elderly (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 2. TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Influenza vaccination for healthcare workers who work with the elderly (Review) i Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 3. [Intervention Review] Influenza vaccination for healthcare workers who work with the elderly Roger E Thomas1 , Tom Jefferson2 , Vittorio Demicheli3 , Daniela Rivetti4 1 Department of Medicine, University of Calgary, Calgary, Canada. 2 Vaccines Field, The Cochrane Collaboration, Roma, Italy. 3 Health Councillorship - Servizio Regionale di Riferimento per l’Epidemiologia, SSEpi-SeREMI - Cochrane Vaccines Field, Regione Piemonte - Azienda Sanitaria Locale ASL AL, Torino, Italy. 4 Public Health Department, Servizio di Igiene e Sanita’ Pubblica, Asti, Italy Contact address: Roger E Thomas, Department of Medicine, University of Calgary, UCMC, #1707-1632 14th Avenue, Calgary, Alberta, T2M 1N7, Canada. rthomas@ucalgary.ca. (Editorial group: Cochrane Acute Respiratory Infections Group.) Cochrane Database of Systematic Reviews, Issue 2, 2009 (Status in this issue: Unchanged, commented) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DOI: 10.1002/14651858.CD005187.pub2 This version first published online: 19 July 2006 in Issue 3, 2006. Last assessed as up-to-date: 7 May 2006. (Help document - Dates and Statuses explained) This record should be cited as: Thomas RE, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD005187. DOI: 10.1002/14651858.CD005187.pub2. ABSTRACT Background Healthcare workers (HCWs) (health professionals, nurses, doctors, cleaners and porters), have substantial rates of clinical and sub- clinical influenza during influenza seasons and may transmit influenza to those in their care, especially the elderly. Objectives To identify studies assessing the effects of vaccinating HCWs on the incidence of influenza, influenza-like-illness (ILI) and its compli- cations on elderly residents in long-term facilities. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews and the NHS Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2006, issue 1); MEDLINE (January 1966 to Week 1, February 2006); EMBASE (1974 to March 2006); Biological Abstracts (1969 to December 2004); and Science Citation Index- Expanded (1974 to March 2006). Selection criteria Comparative randomised and non-randomised studies reporting the effects of influenza vaccines on the incidence of viral infections in institutions for the elderly, in any vaccination schedule for HCWs caring for elderly residents in long-term facilities aged 60 years or older. Data collection and analysis Two review authors independently extracted data and assessed the methodological quality using criteria from the Cochrane Reviewers’ Handbook and the Newcastle-Ottawa scale (for non-randomised studies). Main results We included two cluster randomised controlled trials (C-RCT) and one cohort study. Staff vaccination appears to have significant effect against ILI (absolute vaccine efficacy (VE) 86%, 95% confidence interval (CI) 40% to 97%) only when patients are also vaccinated; if Influenza vaccination for healthcare workers who work with the elderly (Review) 1 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 4. patients are not vaccinated, staff immunisation shows no effect (based on one C-RCT). Based on a small number of observations from two C-RCTs, the vaccines have no efficacy against influenza (odds ratio (OR) 0.86, 95% CI 0.44 to 1.68) or lower respiratory tract infections (OR 0.70, 95% CI 0.41 to 1.20) but were effective against deaths from pneumonia (VE 39%, 95% CI 2% to 62%) and deaths from all causes (VE 40%, 95% CI 27% to 50%). All findings must be interpreted with caution given the presence of selection bias. Authors’ conclusions There is no credible evidence that vaccination of healthy people under the age of 60, who are HCWs caring for the elderly, affects influenza complications in those cared for. However, as vaccinating the elderly in institutions reduces the complications of influenza and vaccinating healthy persons under 60 reduces cases of influenza, those with the responsibility of caring for the elderly in institutions may want to increase vaccine coverage and assess its effects in well-designed studies. PLAIN LANGUAGE SUMMARY There is no high quality evidence that vaccinating healthcare workers reduces the incidence of influenza or its complications in the elderly in institutions There is evidence that vaccinating the elderly has a modest impact on the complications from influenza. There is also high quality evidence that vaccinating healthy adults under 60 (which includes healthcare workers) reduces cases of influenza. Both the elderly in institutions and the healthcare workers who care for them could be vaccinated for their own protection, but an incremental benefit of vaccinating healthcare workers for the benefit of the elderly cannot be proven without better studies. BACKGROUND There are two non-Cochrane systematic reviews of the effects of influenza vaccines in the elderly. Gross 1995 is a decade old and Healthcare workers (HCWs) - such as nurses, doctors, other health its conclusions may be affected by exclusion of recent evidence. professionals, cleaners and porters - have substantial rates of clinical Vu 2002 has methodological weaknesses (excluding studies with and sub-clinical influenza during influenza seasons (Elder 1996; denominators smaller than 30 and quantitative pooling of studies Ruel 2002). HCWss often continue to work when infected with with different designs), which are likely to undermine the conclu- influenza, raising the possibility of transmitting influenza to those sions. A systematic review by Jordan 2004 et al of the effects of in their care (Coles 1992; Weingarten 1989; Yassi 1993). Elderly vaccinating HCWs against influenza on high risk elderly, reports people (aged 60 or older) in institutions such as long-stay hos- significantly lower mortality in the elderly (13.6% versus 22.4%, pital wards and nursing homes are at risk of influenza, especially odds ratio (OR) 0.58, 95% confidence interval (CI) 0.4 to 0.84) if affected with multiple pathologies (Fune 1999; Jackson 1992; when vaccinating HCWs. At present, Cochrane reviews assess- Muder 1998; Nicolle 1984). One possible way to prevent the ing the effects of influenza vaccines in children (Jefferson 2005a; spread to institutionalised elderly may be vaccinating health care Smith 2004), the elderly (Jefferson 2005b; Rivetti 2005), healthy workers (HCWs). The CDC Advisory Committee on Immuniza- adults (Demicheli 2004), people affected with chronic obstructive tion Practices (ACIP) recommends vaccination of all HCWss ( pulmonary disease (Poole 2000), asthma (Cates 2003) and cystic Harper 2004). However, only 36% of HCWss in the US have fibrosis (Tan 2000) show modest benefits or a lack of evidence. been vaccinated (CDC 2003) and 35% of staff in long-term fa- cilities in Canada in 1999 (Stevenson 2001). Nurses and (in some There are two non-Cochrane systematic reviews of the effects of institutions) physicians tend to have lower influenza vaccination influenza vaccines in the elderly. Gross 1995 is a decade old and rates than other HCWss. This relatively low uptake may partly be its conclusions may be affected by exclusion of recent evidence. a reflection of doubts as to the vaccines’ effectiveness (its ability to Vu 2002 has methodological weaknesses (excluding studies with prevent influenza-like illness - ILI) and efficacy (its ability to pre- denominators smaller than 30 and quantitative pooling of studies vent influenza) (Ballada 1994; Campos 2002-3; Ludwig-Beymer with different designs), which are likely to undermine the con- 2002; Martinello 2003; Quereshi 2004). The design and execu- clusions. A systematic review by Jordan 2004 et al of the effects tion of campaigns to increase vaccination rates are also important of vaccinating HCWs against influenza on high risk elderly, re- (Doebbeling 1997; NFID 2004; Russell 2003a; Russell 2003b). ports significantly lower mortality in the elderly (13.6% versus Influenza vaccination for healthcare workers who work with the elderly (Review) 2 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 5. 22.4%, odds ratio (OR) 0.58, 95% confidence interval (CI) 0.4 Primary outcome measures for preventive efficacy and to 0.84) when vaccinating . At present, Cochrane reviews assess- effectiveness ing the effects of influenza vaccines in children (Jefferson 2005a; 1. Cases of ILI clinically defined from a list of likely respi- Smith 2004), the elderly (Jefferson 2005b; Rivetti 2005), healthy ratory and systemic signs and symptoms within the epi- adults (Demicheli 2004), people affected with chronic obstructive demic period (the six-month winter period if not better pulmonary disease (Poole 2000), asthma (Cates 2003) and cystic specified). fibrosis (Tan 2000) show modest benefits or a lack of evidence. 2. Cases of influenza confirmed by means of viral isola- tion and/or serological supporting evidence and a list of likely respiratory symptoms. OBJECTIVES 3. Cases of influenza or ILI admitted to hospital. 4. Deaths by all causes. To identify and summarise comparative studies assessing the effects 5. Deaths caused by influenza or by its complications. of vaccinating HCWs on the incidence of influenza, influenza- 6. Any other direct or indirect indicator of disease impact like-illness (ILI) and its complications in elderly residents in long (days of illness, resources consumption, complications, term facilities. To identify side-effects of vaccination, if data are etc). available. Studies reporting only serological outcomes in the absence of symptoms were excluded. Outcomes for HCWss were not considered. METHODS Search methods for identification of studies Criteria for considering studies for this review We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews and Types of studies the NHS Database of Abstracts of Reviews of Effects (DARE) Comparative randomised and non-randomised studies (cohort or (The Cochrane Library 2006, issue 1); MEDLINE (January 1966 case-control studies) reporting exposure and outcomes by vaccine to Week 1, February 2006); EMBASE (1974 to March 2006); status. Biological Abstracts (1969 to December 2005); and Science Cita- tion Index-Expanded (1974 to March 2006). MEDLINE was searched using the following search terms in com- Types of participants bination with stages I, II and III of the highly sensitive search strat- HCWs (nurses, doctors, nursing and medical students, other egy defined by the Cochrane Collaboration and detailed in Ap- health professionals, cleaners, porters and volunteers who have pendix 5b of the Cochrane Reviewers’ Handbook (Deeks 2005). regular contact with the elderly) of all ages caring for elderly resi- MEDLINE (OVID) dents (aged 60 years or older) in closed institutions such as nursing 1 exp INFLUENZA/ homes, long-term care institutions or acute hospitals. 2 influenza.mp. 3 or/1-2 Types of interventions 4 exp VACCINES/ 5 exp VACCINATION/ Vaccination of HCWss with any influenza vaccine given indepen- 6 (immuniz$ or immunis$).mp. dently, in any dose, preparation, or time schedule, compared with 7 vaccin$.mp. placebo or with no intervention. 8 or/4-7 Studies on vaccinated elderly are included in the review of the 9 3 and 8 effects of influenza vaccines in the elderly (Jefferson 2005b; Rivetti 10 exp Influenza Vaccine/ 2005); whereas the effects of vaccination in healthy adults such as 11 (influenz$ adj (vaccin$ or immun$)).mp. HCWss are assessed in the review by Demicheli et al (Demicheli 12 or/10-11 2004). 13 9 or 12 14 exp Health Personnel/ Types of outcome measures 15 (health personnel or healthcare personnel or health care per- sonnel).mp. 16 (health worker$ or healthcare worker$ or health care Outcomes for the elderly worker$).mp. Influenza vaccination for healthcare workers who work with the elderly (Review) 3 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 6. 17 (healthcare provider$ or health care provider$).mp. domised studies in relation to the presence of potential con- 18 (health practitioner$ or healthcare practitioner$ or health care founders using the appropriate Newcastle-Ottawa Scales (NOS) ( practitioner$).mp. Wells 2005). We used quality at the analysis stage as a means of 19 health employee$.mp. interpretation of the results. 20 medical staff.mp. We assigned risk of bias categories on the basis of the number of 21 (doctor$ or physician$).mp. NOS items judged inadequate in each study: low risk of bias - up to 22 (allied health adj (staff or personnel)).mp. one inadequate item; medium risk of bias - up to three inadequate 23 paramedic$.mp. items; high risk of bias - more than three inadequate items; very 24 nursing staff.mp. high risk of bias - when there was no description of methods. The 25 nurse$.mp. NOS asks whether all possible precautions against confounding 26 nursing auxiliar$.mp. have been taken by the study designers and links study quality to 27 hospital personnel.mp. the answer. We translated the number of inadequately reported or 28 hospital staff.mp. conducted items into categories of risk of bias. 29 hospital worker$.mp. The other two review authors (VD, DR) checked data extraction 30 exp HOSPITALS/ and quality assessment. 31 exp Long-Term Care/ 32 exp Residential Facilities/ Arbitration procedure 33 nursing home$.mp. Disagreements on inclusion or methodological quality of studies 34 (institution$ adj3 elderly).mp. were resolved by discussion among the review authors. 35 or/14-34 36 13 and 35 This strategy was adapted to search the other electronic databases. Data collection See Appendix 1 for the EMBASE search strategy. There were no The following data were extracted in duplicate onto standard language or publication restrictions. The search of CENTRAL in- Cochrane Vaccines Field data extraction forms: cluded trial reports identified in the systematic search by hand of period study conducted; the journal Vaccine. To identify additional published and unpub- country or countries of study; lished studies the Science Citation Index-Expanded was used to number of studies included in this paper; identify articles that cite the relevant studies. The relevant stud- funding source; ies were also keyed into PubMed and the Related Articles feature paper/abstract numbers of other studies with which these data are used. linked; Bibliographies of all relevant articles were obtained, and any reviewer’s assessment of study design; published review and proceedings from relevant conferences methods; was assessed for additional studies. We explored Internet participants; sources in December 2005: NHS National Research Regis- interventions and exposure; ter (http://www.update-software.com/national/); the Meta-regis- outcomes (serological, effectiveness, safety); ter of Clinical Trials (http://www.controlled-trials.com/) the dig- notes or comments; ital dissertations website (http://wwwlib.umi.com/dissertations). methodological quality assessment. The Vaccine Adverse Event Reporting System website was searched (http://www.vaers.org). We contacted first or corresponding au- Data synthesis thors of relevant studies to identify further published or unpub- We structured two comparisons: studies with an experimental de- lished trials. sign and study without experimental design. Whenever data pre- sented in the study allowed it, we carried out subgroup analysis according to elderly residents’ vaccination status. We assessed the Data collection and analysis following outcomes which arose during the influenza season: ILI; Two review authors (RT, TOJ) applied inclusion criteria to all influenza infections; lower respiratory tract infections; deaths from identified and retrieved articles and extracted data from included pneumonia and all-cause mortality. Only the last outcome allowed studies on standard Cochrane Vaccines Field forms. Assessment a comparison with two studies; for each of the remaining out- of methodological quality for randomised controlled trials (RCTs) comes only data from one study were available. Efficacy (against was carried out using criteria from the Cochrane Reviewers’ Hand- influenza) and effectiveness (against ILI) (effects) estimates were book (Deeks 2005). We assessed studies according to randomi- summarised as relative risk (RR) or odds ratio (OR) within 95% sation, generation of the allocation sequence, allocation conceal- confidence intervals (CI) (in brackets after the summary estimate). ment, blinding and follow up. We assessed quality of non-ran- Absolute vaccine efficacy (VE) was expressed as a percentage using Influenza vaccination for healthcare workers who work with the elderly (Review) 4 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 7. the formula: VE = 1 - RR whenever significant. When statistical and were more likely to receive influenza vaccine (no significance significance was not achieved we reported the relevant RR or OR. level stated), and due to missing data these differences could not be adjusted for other than by estimation. The study is thus at intermediate risk of bias. The Potter 1997 and Carman 2000 C-RCTs can be regarded as RESULTS investigations in the same geographical area with an unknown overlap, because with the high mortality rate in the LTCHs it is unlikely that many patients participated in both studies; only three of the LTCHs in the Potter study (Potter 1997) were included Description of studies in the Carman RCT (Carman 2000) because some of the homes See: Characteristics of included studies; Characteristics of excluded were closed down (e-mail communication from Dr. Stott), but the studies. continuity of staff between the institutions is unknown. Due to the comprehensive nature of the Cochrane review on the Oshitani 2000 is at high risk of bias because of inconsistencies in effects of influenza vaccines in the elderly (Jefferson 2005b; Rivetti reporting of denominators, lack of clear definition of vaccine cov- 2005), we carried out a review with a very focussed study ques- erage rates among HCWss, unclear ascertainment of vaccination tion and benefited from extensive searches which generated a large status and comparability of hemicohorts, differential criteria for number of “hits” but a relatively low yield of included studies. diagnosing ILI, the lack of laboratory confirmation and the mix- Among 312 reports retrieved for detailed assessment in the re- ing of two types of healthcare facilities, one which is for elderly view on the effects of influenza vaccines in the elderly (Jefferson patients the other for elderly with severe conditions. Facilities with 2005b; Rivetti 2005), we identified five studies possibly meeting higher vaccination rates might also have practiced other preven- our inclusion criteria - two cluster randomised studies (C-RCT) ( tive measures, such as hand washing, limitation of visitors during Carman 2000; Potter 1997) and three cohorts studies (Isaacs 1997; influenza epidemics or isolation of patients. These practices may Oshitani 2000; Yassi 1993). We included two C-RCTs (Carman have had an impact on the outcome but are not reported. 2000; Potter 1997) and one cohort study (Oshitani 2000). See the description of the studies in the ’Characteristics of included studies’ table. Effects of interventions ILI Risk of bias in included studies Potter 1997 and Oshitani 2000 reported data on ILI, but only Potter 1997 has a pragmatic design. There is no description of vac- Potter 1997 defined illness from a list of likely respiratory and cines administered, vaccine matching and background influenza systemic signs and symptoms. According to Potter 1997’s data, epidemiology. The risk of bias is medium. staff vaccination appears to have significant effect (VE 86%, 95% In Carman 2000 potential sources of bias were: CI 40% to 97%) only when patients are vaccinated too. If pa- - selection bias: the total number of long-term care hospitals tients were not vaccinated, staff immunisation showed no effect. (LTCHs) in West and Central Scotland is not stated. However in Oshitani 2000 shows a significant effect quite apart from the vac- the LTCHs in which HCWss were offered vaccination, residents cination of residents (overall VE 61%, 95% CI 54% to 68%), but had higher Barthel scores; we have to remember the high risk of bias of this study. - performance bias: only 51% of HCWss in the arm received vac- cine in the LTCHs where vaccine was offered, and 4.8% where it Influenza was not; 48% of patients received vaccine in the arm where HCWss were offered vaccination, and 33% in the arm where HCWss were Potter 1997 and Carman 2000 reported data on influenza cases not; polymerase chain reaction (PCR) samples were obtained from among patients. Although it was not a clinical outcome (viral only 17% of deaths; surveillance was carried out separately from clinical symptoms) - attrition bias (no attrition data stated); and specimens were obtained from some residents only, we consid- - detection bias (four samples from each patient surveyed were ered this outcome as it points out the ability of staff vaccination to planned from protocol: 1798 samples were obtained from 719 stop transmission of the virus to the community. Even though the patients (2.5 samples/patient)); statistical power may also have small number of observations suggests some caution, the vaccine been a problem as the detection rate of 6.7% was lower than the does not appear efficacious (OR 0.86, 95% CI 0.44 to 1.68). estimated rate of 25% used in the power calculation; - statistical bias: the analysis was not corrected for clustering, unlike Lower respiratory tract infections the Potter 1997 pilot; in the LTCHs where HCWss were offered Only the Potter 1997 study reports this outcome on which the vaccination, the patients had significantly higher Barthel scores vaccine had no significant effect (OR 0.70, 95% CI 0.41 to 1.20). Influenza vaccination for healthcare workers who work with the elderly (Review) 5 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 8. Deaths from pneumonia 65 years or older the mortality attributable to pneumonia or in- Only the Potter 1997 study reported this outcome: VE 39%, 95% fluenza never exceeded 10% of all deaths during those winters. CI 2 to 62. The Cochrane review by Demicheli 2004 in healthy adults un- der 60 found that for vaccines with WHO or government-rec- All deaths ommended content compared with placebo the risk difference of Potter 1997 and Carman 2000 reported data on deaths for all experiencing ILI was small, 6% (95% CI 4% to 8%), with reduc- causes (1239 observations in the treatment arm and 1257 obser- tions of 3%, 7% and 9% for the live aerosol, inactivated parenteral vations in the control arm). The effect of the vaccine is significant: and inactivated aerosol vaccines respectively. The overall estimate (VE 40%, 95% CI 27% to 50%). of vaccine efficacy was 22% (95% CI 14% to 30%). For cases of influenza, vaccine efficacy was higher at 48% (95% CI 24% to 64%) for live aerosol vaccines and 70% (95% CI 56% to 80%) for inactivated parenteral vaccines. When the vaccine matched the circulating strain the risk difference compared to placebo for ILI DISCUSSION was still modest, 9% (95% CI 5% to 12%), and overall vaccine We identified only two cluster-randomised controlled trials and efficacy was 33% (95% CI 20% to 44%). Against influenza cases, one cohort study to answer the question of whether vaccinat- vaccine efficacy was higher at 75% (95% CI 62% to 84%). Thus ing healthcare workers against influenza protects elderly institu- vaccination provides some protection to the healthy under 60s, tionalised patients. Each of these three studies had methodologi- particularly if the vaccine matches the circulating strain and the cal problems that necessitate caution when drawing conclusions. outcome of interest is serologically proven influenza. Other sources of information about whether vaccination reduces cases of influenza in the healthy under 60s and in the elderly are the Cochrane reviews (Demicheli 2004; Jefferson 2005b; Rivetti AUTHORS’ CONCLUSIONS 2005). The review by Jefferson et al (Jefferson 2005b) found that in homes for the elderly, well-matched influenza vaccines prevented Implications for practice pneumonia (VE 46%, 95% CI 30% to 58%), hospital admis- sion for pneumonia (VE 45%, 16% to 64%), and deaths from There is no credible evidence that vaccination of healthy HCWss influenza or pneumonia (VE 42%, 17% to 59%) and reduced all (under 60 years of age) who are caring for the elderly, affects in- cause mortality (VE 60%, 95% CI 23% to 79%). Thus vaccina- fluenza complications in those being cared for. However, as vac- tion provides some protection to the elderly from the complica- cinating the elderly in institutions reduces the complications of tions of influenza. The authors also detected a possible gradient influenza and vaccinating healthy persons under 60 years of age of effectiveness, in which vaccines have little effect on cases of reduces cases of influenza, those with the responsibility of caring ILI, but have greater effect on its complications. The authors con- for the elderly in institutions may want to increase vaccine cover- cluded that differential vaccine uptake with the resulting selection age and assess its effects in well-designed studies. bias is a likely explanation for the greater effectiveness of influenza vaccines in preventing deaths from all causes. Our results in this Implications for research review show a similar picture: no effect on ILI or influenza cases Well-designed, credible evaluations of the impact on elderly res- but a significant protection against deaths from all causes. The idents of vaccinating their carers against influenza are urgently possible bias is evident in Potter 1997, which shows inconsisten- needed. These RCTs should have minimal risk of bias from se- cies in outcome gradients, as reported in the Additional table. In lection, performance, attrition and detection biases and should the population under observation, Potter 1997 et al reported 216 be adequately powered. They should carefully define and measure cases of suspected viral illness, 64 cases of ILI, 55 cases of pneumo- outcomes including ILI, serologically-proven influenza, lower res- nia, 72 deaths from pneumonia and 148 deaths from all causes; piratory tract infection, death from pneumonia, cause of hospital- in the sub-population of both vaccinated staff and patients, Potter isation and all-cause mortality. 1997 et al reported 24 cases of suspected viral illness, 2 cases of ILI, 7 cases of pneumonia, 10 deaths from pneumonia and 25 deaths from all causes. As these gradients are not plausible, the effect on all-cause mortality is likely to reflect a selection bias rather than a ACKNOWLEDGEMENTS real effect of vaccination. Population studies provide an estimate of the contribution that influenza vaccination of elderly people Professor David J. Stott, Academic Section of Geriatric Medicine, can make in reducing total annual mortality. Simonsen et al ( Glasgow Royal Infirmary, UK provided supplementary informa- Simonsen 2006) obtained data from US national multiple-cause- tion on the Potter 1997 and Carman 2000 studies. The au- of-death databases for 1968 to 2001 and found that for those aged thors wish to thank the following people for commenting on the Influenza vaccination for healthcare workers who work with the elderly (Review) 6 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 9. draft review: Mary Kim, Margaret Russell, Rob Ware and George Swingler. REFERENCES References to studies included in this review Coles 1992 Coles FB, Balzano GJ, Morse DL. An outbreak of influenza A Carman 2000 {published data only} (H3N2) in a well-immunized nursing home population. Journal of Carman WF, Elder AG, Wallace LA, McAulay K, Walker A, Murray the American Geriatrics Society 1992;40:589–92. GD, et al.Effects of influenza vaccination of health-care workers on Deeks 2005 mortality of elderly people in long-term care: a randomised con- Deeks JJ, Higgins JPT, Altman DG. Analysing and presenting results. trolled trial. Lancet 2000;355(9198):93–7. In: Alderson P, Green S, Higgins J editor(s). Cochrane Handbook Oshitani 2000 {published data only} for Systematic Reviews of Interventions 4.2.5 [updated March 2005]; Oshitani H, Saito R, Seki N, Tanabe N, Yamazaki O, Hayashi S, et Section 8. Chichester, UK: John Wiley & Sons, Ltd, 2005. al.Influenza vaccination levels and influenza-like illness in long-term- care facilities for elderly people in Niigata, Japan, during an influenza Demicheli 2004 A (H3N2) epidemic. Infection Control and Hospital Epidemiology Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for prevent- 2000;21(11):728–30. ing influenza in healthy adults. Cochrane Database of Systematic Re- views 2004, Issue 3. [DOI: 10.1002/14651858.CD001269.pub3] Potter 1997 {published data only} Potter J, Stott DJ, Roberts MA, Elder AG, O’Donnell B, Knight Doebbeling 1997 PV, et al.Influenza vaccination of health care workers in long-term- Doebbeling BN, Edmond MB, Davis CS, Woodin JR, Zeitler RR. care hospitals reduces the mortality of elderly patients. Journal of Influenza vaccination of health care workers: Evaluation of factors Infectious Diseases 1997;175(1):1–6. that are important in acceptance. Preventive Medicine 1997;26:68– 77. References to studies excluded from this review Elder 1996 Elder AG, O’Donnell B, McCruden EAB, Symington IS, Carman Isaacs 1997 {published data only} WF. Incidence and recall of influenza in a cohort of Glasgow health- Isaacs S, Dickinson C, Brimmer G. Outbreak of influenza A in an care workers during the 1993-4 epidemic: results of serum testing Ontario nursing home. Canada Communicable Disease Report 1997; and questionnaire. BMJ 1996;313(7067):1241–2. 23(14):105–8. Fune 1999 Yassi 1993 {published data only} Fune L, Shua-Haim JR, Ross JS, Frank E. Infectious disease among Yassi A, Mcgill M, Holton C, Nicolle L. Morbidity, cost and role residents of nursing homes. Annals of Long-term Care 1999;7:410–7. of health care worker transmission in an outbreak in a tertiary care hospital. Canadian Journal of Infectious Diseases 1993;4:42–56. Gross 1995 Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The Additional references efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature. Annals of Internal Medicine 1995;123(7): Ballada 1994 518–27. Ballada D, Biasio LR, Cascio G, et al.Attitudes and behavior of health Harper 2004 care personnel regarding influenza vaccination. European Journal of Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention Epidemiology 1994;10:63–8. and control of influenza: recommendations of the Advisory Com- Campos 2002-3 mittee on Immunization Practices (ACIP). MMWR Recommenda- Campos W, Jalaludin BB. Predictors of influenza vaccination tions & Reports 2004;53(RR-6):1–40. amongst Australian nurses. Australian Journal of Advanced Nursing Jackson 1992 2002–2003;20:19–21. Jackson MM, Fierer J, Barrett-Connor E, Fraser D, Klauber MR, Cates 2003 Tatch R, et al.Intensive surveillanced for infections in a three-year Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing study of nursing home patients. American Journal of Epidemiology influenza in people with asthma. Cochrane Database of Systematic 1992;135:685–96. Reviews 2003, Issue 4. [DOI: 10.1002/14651858.CD000364.pub3] Jefferson 2005a CDC 2003 Jefferson T, Smith S, Demicheli V, Harnden A, Rivetti A, Di Pietran- Centers for Disease Control. Prevention and control of influenza. tonj C. Assessment of the efficacy and effectiveness of influenza vac- Recommendations of the Advisory Committee on Immunization cines in healthy children: systematic review. Lancet 2005;365:773– Practices (ACIP). MMWR 2003;RR 8:1–34. 80. Influenza vaccination for healthcare workers who work with the elderly (Review) 7 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 10. Jefferson 2005b A/H3N in institutionalized aged. Role of immunological status to Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, influenza vaccine and possible implication of caregivers in the trans- Demicheli V. Efficacy and effectiveness of influenza vaccines in el- mission [Infections groupées à virus respiratoire syncytial et à in- derly people: systematic review. Lancet 2005;366:1165–74. fluenzavirus A/H3N2 chez des sujets âgés en institution. Influence Jordan 2004 du status vaccinal anti–grippal et implication possible des soignants Jordan R, Wake B, Hawker J, Boxall E, Fry-Smith A, Chen Y-F, et dans la transmission]. Presse Medicale 2002;31(8):349–55. al.Influenza vaccination of health care workers (HCW) to reduce in- Russell 2003a fluenza-related outcomes in high risk patients: a systematic review of Russell ML, Henderson EA. The measurement of influenza vaccine clinical and cost-effectiveness. WMHTAC. Vol. 88, West Midlands coverage among health care workers. American Journal of Infection Health Technology Assessment Collaboration (WMHTAC), 2004. Control 2003;31:457–61. Ludwig-Beymer 2002 Russell 2003b Ludwig-Beymer P, Gerc SC. An influenza prevention campaign: the Russell ML, Thurston WE, Henderson EA. Theory and models for employee perspective. Journal of Nursing Care Quality 2002;16:1– planning and evaluating institutional influenza prevention and con- 12. trol programs. American Journal of Infection Control 2003;31:336– Martinello 2003 41. Martinello RA, Jones L, Topal JE. Correlation between healthcare Simonsen 2006 workers’ knowledge of influenza vaccine and vaccine receipt. Infection Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, Control and Hospital Epidemiology 2003;24:845–7. Miller MA. Impact of influenza vaccination on seasonal mortality in Muder 1998 the US elderly population. Annals of Internal Medicine 2006;165: Muder RR. Pneumonia in residents of long-term care facilities: Epi- 265–72. demiology, etiology, management, and prevention. American Journal Smith 2004 of Medicine 1998;105:319–30. Smith S, Demicheli V, Jefferson T, Harnden A, Matheson N, Di NFID 2004 Pietrantonj C. Vaccines for preventing influenza in healthy chil- National Foundation for Infectious Diseases. Improving influenza dren. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: vaccination rates in 10.1002/14651858.CD004879.pub3] health care workers. www.nfid.org/publications/hcwmonograph.pdf (accessed 1 November 2004). Bethesda, Maryland, USA: National Stevenson 2001 Foundation for Infectious Diseases, 2004. Stevenson GG, McArthur MA, Naus M, Abraham E, McGeer AJ. Prevention of influenza and pneumococcal pneumonia in Canadian Nicolle 1984 long-term care facilities: How are we doing?. Canadian Medical Nicolle LE, McIntyre M, Zacharia H, MacDonell JA. Twelve-month Association Journal 2001;164:1413–9. surveillance of infections in institutionalized elderly men. Journal of the American Geriatrics Society 1984;32:513–9. Tan 2000 Tan A, Bhalla P, Smyth R. Vaccines for preventing influenza in people Poole 2000 with cystic fibrosis. Cochrane Database of Systematic Reviews 2000, Poole PJ, Chacko E, Wood-Baker RWB, Cates CJ. Influenza Issue 1. [DOI: 10.1002/14651858.CD001753] vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2000, Issue 3. [DOI: Vu 2002 10.1002/14651858.CD002733.pub2] Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the Quereshi 2004 community. Vaccine 2002;20(13-14):1831–6. Quereshi AM, Hughes NJM, Murphy E, Primrose WR. Factors in- fluencing uptake of influenza vaccine among hospital-based health Weingarten 1989 care workers. Occupational Medicine 2004;54:197–201. Weingarten S, Riedinger M, Bolton LB, Miles P, Ault M. Barriers to Rivetti 2005 influenza vaccination acceptance: a survey of physicians and nurses. Rivetti D, Demicheli V, Di Pietrantonj C, Jefferson TO, American Journal of Infection Control 1989;17:202–7. Thomas R. Vaccines for preventing influenza in the elderly. Wells 2005 Cochrane Database of Systematic Reviews 2005, Issue 1. [DOI: Wells GA, Shea B, O’Connell D, et al.The Newcastle-Ot- 10.1002/14651858.CD004876.pub2] tawa Scale (NOS) for assessing the quality of nonrandomised Ruel 2002 studies in meta-analyses. http://www.ohri.ca/programs/clinical_ Ruel N, Odelin MF, Jolly J, Momplot C, Diana MC, Bourlet T, et epidemiology/oxford web.ppt Accessed 2 September 2005. al.Outbreaks due to respiratory syncytial virus and influenza virus ∗ Indicates the major publication for the study Influenza vaccination for healthcare workers who work with the elderly (Review) 8 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 11. CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Carman 2000 Methods Cluster randomised study conducted in Scotland during the 1996 -1997 influenza season. The study identified 10 long-term-care geriatric hospitals (LTCH) in West and Central Scotland with a policy of vaccinating all patients against influenza if they had no contraindications, and then only on the request of the patients or their relatives. Pairs of hospitals in each of these clusters were matched on patient enrolment and then in a Latin square design were randomised by a table of random numbers for the HCWss to be offered influenza vaccination or not Anonymous questionnaires were sent to ward nurses on March 31 1997 to ask if they had received influenza vaccination, and this data was used to estimate vaccine acceptance for all HCWss in hospitals where influenza vaccine had not been offered to HCWss. In each hospital a random sample chosen by computer of 50% patients was selected for virological monitoring Data from the Scottish Centre for Infection and Epidemiological Health and from GP’s were used to define the start of the influenza season. Combined nasal and throat swabs were taken from patients every 2 weeks from December 14 1996 to February 14 1997. Opportunistic samples were also taken from patients whom the ward nurses thought had influenza. Samples were taken within 12 hours of death of any patient who died. Samples were analysed by RT-PCR analysis Results were summarised for the two clusters. Hospitals were not well-matched for patient vaccination rates and Barthel scores, and post-hoc statistical adjustments could not be made because of missing data. The outcome was the empirical logic of mortality for each cluster (= natural logarithm of the odds on death) Participants Seven hundred and forty nine participants were residents of facilities in the arm in which 1217 HCWs were offered vaccination (620 accepted) and 688 in the arm in which HCWs were not offered vaccination. Day and night nurses, doctors, therapists, porters and ancillary staff (including domestic staff and ward cleaners) were offered influenza vaccination Interventions Influenza vaccination type, dosage and route are not described, although there was a good match in the study year between the prevailing strain and the vaccine strains Outcomes Influenza infections (nose and throat swabs every two weeks on 50% of patients: it is not a clinical outcome but was used to investigate the viral circulation in the facility) Death and PCR + influenza A or B. This outcome was not used in the analysis: PCR samples were obtained from only a small proportion of the deaths Death for all causes Notes The situation that 10 LTCHs had a policy of routinely vaccinating residents for influenza vaccination and 10 did not, permitted a Latin square design RCT of offering influenza vaccination or not to HCWss within each of these clusters Analysis was not according to intention to treat Risk of bias Influenza vaccination for healthcare workers who work with the elderly (Review) 9 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 12. Carman 2000 (Continued) Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear Oshitani 2000 Methods Prospective cohort study assessing the effectiveness of influenza vaccination levels in patients of long- term nursing care facilities (LTCFs) by vaccination coverage rates of HCWs (less than 10 or more than 10 vaccinated HCWss per facility), in Niigata, Japan. Niigata Prefecture and Niigata City conducted mandatory surveys of influenza vaccine status and occurrence of ILI every two weeks from January to March 1999. During this period more than 20% of facilities had outbreaks, and more than 10% of residents experienced ILI during an influenza A (H3N2) epidemic All LTCFs in Niigata Prefecture provided reports. Information (assumed questionnaires) included number of residents in each institution, number of vaccinated residents and staff and weekly ILI in residents. No ILI definition is reported Influenza outbreak was defined when 10% of more of the residents reported ILI symptoms Two types of long term care facilities (LTCFs), special nursing homes for the elderly and geriatric health services facilities were used. Both are for the elderly who need constant care, special nursing homes are for the elderly who have more severe conditions Participants Twelve thousand seven hundred and eighty four residents in 149 facilities were included in the study (3933 vaccinated and 6430 not vaccinated). There are inconsistencies in the reported elderly vaccinated denominators. The study also describes outcomes for HCWs by vaccine exposure Interventions Trivalent Influenza Vaccine containing A/Beijing/262/95 (H1N1), A/Sydney/5/97 (H3N2), and B/Mie/1/93, which was a good match against the circulating strain. No mention of pneumococcus vac- cination is made Outcomes ILI, without case definition; there was an ILI outbreak when the number of ILI per week exceeded 10% of the residents Notes The authors conclude that there was a significant impact of influenza in LTCFs in Japan. Outbreaks and numbers of cases were significantly reduced by vaccination of residents and staff, so this measure should be strongly recommended to protect institutionalised elderly people from influenza infections Risk of bias Item Authors’ judgement Description Allocation concealment? No C - Inadequate Influenza vaccination for healthcare workers who work with the elderly (Review) 10 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 13. Potter 1997 Methods Cluster randomised study conducted in Scotland, during the 1994 to 1995 influenza season, in the community. Follow up period was 1/10/94 to 31/3/95. 12 hospitals were randomly allocated to offer vaccination of health care workers or not; facilities were grouped according to the vaccination policy. The vaccination of staff and patients was voluntary The study thus presents data on four sub-populations: - staff and patients not vaccinated - staff not vaccinated, patients vaccinated - staff and patients vaccinated - staff vaccinated and patients not vaccinated Participants 12 hospitals: 1059 hospital’s residents. Observed units were hospital and not patients Interventions Parenteral influenza vaccine. Vaccine strains probably matched the circulating strain Outcomes Influenza infection: paired sera in 225 patients in “patients not vaccinated” arm ILI (defined as a temperature of 37C or more, plus one of the following: new onset cough, coryza, sore throat, malaise, headache, myalgia - reported singly or within the ILI outcome) lower respiratory tract infection (defined as pulmonary crackles, wheeze or tachypnea plus temp 37C or more or a positive sputum and leucocytosis) deaths (from all causes) deaths (from pneumonia) Notes Staff vaccination was incomplete and variable; results were presented by hospitals’ group and not by vaccination status of patients. The authors conclude that vaccination of HCWs was associated with lower mortality and ILI. These benefits were not evident vaccinating patients alone Risk of bias Item Authors’ judgement Description Allocation concealment? Unclear B - Unclear ILI = influenza-like illness HCWs = health care worker LTCH = long-term care hospitals PCR = polymerase chain reaction RCT = randomised controlled trial RT-PCR = reverse-transcriptase polymerase chain reaction Influenza vaccination for healthcare workers who work with the elderly (Review) 11 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 14. Characteristics of excluded studies [ordered by study ID] Isaacs 1997 Data were not presented by HCWss vaccine coverage Yassi 1993 Data were not presented by HCWss vaccine coverage. Vaccine and amantadine were used to control outbreak: aman- tadine acts as confounder Influenza vaccination for healthcare workers who work with the elderly (Review) 12 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 15. DATA AND ANALYSES Comparison 1. HCWs offered vaccination versus HCWs offered no vaccination: experimental design No. of No. of Outcome or subgroup title studies participants Statistical method Effect size 1 ILI 1 1059 Risk Ratio (M-H, Random, 95% CI) 0.39 [0.06, 2.49] 1.1 Vaccinated patients 1 538 Risk Ratio (M-H, Random, 95% CI) 0.14 [0.03, 0.60] 1.2 Unvaccinated patients 1 521 Risk Ratio (M-H, Random, 95% CI) 0.87 [0.49, 1.55] 2 Influenza 2 752 Odds Ratio (M-H, Fixed, 95% CI) 0.86 [0.44, 1.68] 2.1 Unvaccinated patients 1 225 Odds Ratio (M-H, Fixed, 95% CI) 1.37 [0.22, 8.36] 2.2 Vaccinated and 1 527 Odds Ratio (M-H, Fixed, 95% CI) 0.80 [0.39, 1.64] unvaccinated patients 3 Lower respiratory tract infection 1 1059 Risk Ratio (M-H, Random, 95% CI) 0.70 [0.41, 1.20] 3.1 Vaccinated patients 1 538 Risk Ratio (M-H, Random, 95% CI) 0.59 [0.25, 1.40] 3.2 Unvaccinated patients 1 521 Risk Ratio (M-H, Random, 95% CI) 0.78 [0.40, 1.54] 4 Deaths from pneumonia 1 1059 Risk Ratio (M-H, Random, 95% CI) 0.61 [0.38, 0.98] 4.1 Vaccinated patients 1 538 Risk Ratio (M-H, Random, 95% CI) 0.56 [0.27, 1.14] 4.2 Unvaccinated patients 1 521 Risk Ratio (M-H, Random, 95% CI) 0.65 [0.35, 1.23] 5 Deaths from all causes 2 2496 Risk Ratio (M-H, Random, 95% CI) 0.60 [0.50, 0.73] 5.1 Vaccinated patients 1 538 Risk Ratio (M-H, Random, 95% CI) 0.60 [0.39, 0.93] 5.2 Unvaccinated patients 1 521 Risk Ratio (M-H, Random, 95% CI) 0.60 [0.38, 0.95] 5.3 Vaccinated and 1 1437 Risk Ratio (M-H, Random, 95% CI) 0.61 [0.48, 0.76] unvaccinated patients Comparison 2. HCWs offered vaccination versus HCWs offered no vaccination - cohort study No. of No. of Outcome or subgroup title studies participants Statistical method Effect size 1 ILI 1 12742 Risk Ratio (M-H, Random, 95% CI) 0.39 [0.32, 0.46] 1.1 Vaccinated patients 1 6591 Risk Ratio (M-H, Random, 95% CI) 0.39 [0.33, 0.47] 1.2 Unvaccinated patients 1 6151 Risk Ratio (M-H, Random, 95% CI) 0.26 [0.11, 0.62] FEEDBACK Influenza vaccination for healthcare workers who work with the elderly (Review) 13 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 16. Influenza vaccination for healthcare workers who work with the elderly, 5 May 2008 Summary Feedback: The below is not an article in Journal of Infectious Diseases 1997; 175 (1) as cited. Indeed I’v not been able to locate the the study in any other journal, though the study has been cited many times in other studies as well. Potter J, Stott DJ, Roberts MA, Elder AG, O’Donnell B, Knight PV, et al.Influenza vaccination of health care workers in long-term- care hospitals reduces the mortality of elderly patients. Journal of Infectious Diseases 1997;175(1):1-6 Submitter agrees with default conflict of interest statement: I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback. Contributors Thomas Birk Kristiansen Feedback comment added 21 June 2008 WHAT’S NEW Last assessed as up-to-date: 7 May 2006. 21 June 2008 Feedback has been incorporated Feedback comment added. 13 May 2008 Amended Converted to new review format. HISTORY Protocol first published: Issue 2, 2005 Review first published: Issue 3, 2006 CONTRIBUTIONS OF AUTHORS Responsible for the design of the review: Roger Thomas (RT), Tom Jefferson (TOJ), and Vittorio Demichelli (VD). Responsible for the searches: RT and Daniela Rivetti (DR). Responsible for the assessment of study quality and outcomes: RT and TOJ. Responsible for the first draft: RT. Responsible for the final draft: RT, TOJ, VD and DR. Influenza vaccination for healthcare workers who work with the elderly (Review) 14 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • 17. DECLARATIONS OF INTEREST TOJ received fees for consultancies, research and speaking engagements from Glaxo SmithKline Ltd., Roche Ltd., Chiron Ltd., and Sanofi Synthelabo Ltd. INDEX TERMS Medical Subject Headings (MeSH) ∗ HealthPersonnel; Homes for the Aged; Infectious Disease Transmission, Professional-to-Patient [∗ prevention & control]; Influenza, Human [prevention & control; ∗ transmission]; Influenza Vaccines [∗ administration & dosage]; Randomized Controlled Trials as Topic; Vaccines, Inactivated [administration & dosage] MeSH check words Adult; Aged; Humans; Middle Aged Influenza vaccination for healthcare workers who work with the elderly (Review) 15 Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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