Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions

  • Conclusions changed
  • Review
  • Intervention

Authors


Abstract

Background

Healthcare workers' influenza rates are unknown but may be similar to those of the general public. Healthcare workers may transmit influenza to patients.

Objectives

To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older resident in long-term care institutions (LTCIs).

Search methods

We searched CENTRAL 2013, Issue 2, MEDLINE (1966 to March week 3, 2013), EMBASE (1974 to March 2013), Biological Abstracts (1969 to March 2013), Science Citation Index-Expanded (1974 to March 2013) and Web of Science (2006 to March 2013).

Selection criteria

Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare workers caring for individuals aged 60 years or older in LTCIs and the incidence of laboratory-proven influenza and its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 years or older in LTCIs.

Data collection and analysis

Two authors independently extracted data and assessed risk of bias.

Main results

We identified four cluster-RCTs (C-RCTs) (n = 7558) and one cohort study (n = 12,742) of influenza vaccination for HCWs caring for individuals ≥ 60 years in LTCFs. Three RCTs (5896 participants) provided outcome data that met our criteria. These three studies were comparable in study populations, intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition and blinding. The pooled risk difference (RD) from the three cluster-RCTs for laboratory-proven influenza was 0 (95% confidence interval (CI) -0.03 to 0.03) and for hospitalisation was RD 0 (95% CI -0.02 to 0.02). The estimated risk of death due to lower respiratory tract infection was also imprecise (RD -0.02, 95% CI -0.06 to 0.02) in individuals aged 60 years or older in LTCIs. Adjusted analyses which took into account the cluster design did not differ substantively from the pooled analysis with unadjusted data.

Authors' conclusions

The results for specific outcomes: laboratory-proven influenza or its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract illness) did not identify a benefit of healthcare worker vaccination on these key outcomes. This review did not find information on co-interventions with healthcare worker vaccination: hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking healthcare workers with influenza or influenza-like-illness (ILI) not to work. This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in LTCIs. High-quality RCTs are required to avoid the risks of bias in methodology and conduct identified by this review and to test further these interventions in combination.

摘要

背景

為照護老人的健康照護機構工作人員施打流行性感冒疫苗

健康照護機構工作人員(HCW)得到流行性感冒的發生率並不清楚,但可能和一般大眾類似,而且他們可能會進而傳染給病人

目標

目標為找出為照護老人的健康照護機構工作人員施打疫苗的研究,並探討流行性感冒、併發症、及長照機構中大於60歲的居民產生類流感疾病的發生率

搜尋策略

我們搜尋CENTRAL(考科藍資料庫2009年第3期),其中包含了Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE(1966到2009), EMBASE(1974到2009)及Biological Abstracts and Science Citation IndexExpanded.

選擇標準

隨機控制試驗(RCTs),及非隨機控制試驗,試驗內容為替長照機構中照護60歲以上老人的健康照護機構工作人員施打流感疫苗,並探討流行性感冒(經實驗室證實)的發生率,及類流感疾病的併發症

資料收集與分析

二位作者獨立摘錄資料及評估偏差的風險性

主要結論

我們找出4個群集性隨機對照試驗(CRCTs)(有7558人)及1個世代研究(有12742人),內容都是評估為健康照護機構工作人員(照護長照機構中60歲以上老人)施打疫苗的效果. 從3個群集性隨機對照試驗的資料整合分析發現對下列特定結果沒有效益:經實驗室檢查證實的流感,肺炎或肺炎造成的死亡; 而針對非特定結果,則發現為健康照護機構工作人員施打疫苗可減少類流感疾病;由1個群集性隨機對照試驗則發現為健康照護機構工作人員施打疫苗可減少尋求家庭醫師諮詢;而由3個群集性隨機對照試驗的資料整合則發現施打疫苗可減少60歲以上老人各種原因的死亡率

作者結論

施打疫苗對特定結果沒有效益:包括經實驗方法確診的流感、肺炎、及肺炎造成的死亡, 但對非特定結果卻有效益: 包括減少因類流感疾病尋求家庭醫師協助, 及減少60歲以上老人的總死亡率。會造成這些非特定結果的原因很難判讀, 因為類流感疾病可由許多病原引起, 而且冬季流行的流感造成60歲以上老人的死亡,占總死亡率不到10%。我們關注的還是疫苗能不能預防經實驗方法確診的流感、肺炎、及肺炎造成的死亡, 而我們無法下此結論。 我們找出的研究都有偏差的高度風險. 有些健康照護機構工作人員並沒有接種疫苗, 原因包括他們不認為他們具有風險, 懷疑疫苗的效果, 或是擔心疫苗的副作用。除了為健康照護機構工作人員施打疫苗外, 這篇綜合性評論並沒有找到可共同介入的做法, 如洗手,戴口罩,早期確診流感, 隔離, 避免新居民入住, 抗病毒藥物使用, 及要求健康照護機構工作人員出現類流感症狀時不要上班, 我們的結論是目前沒有證據指出為健康照護機構工作人員施打疫苗可避免長照機構的老年居民得到流行性感冒, 未來仍需要高品質的隨機對照試驗來避免方法學或研究執行層面的偏差, 以及測試這些共同介入做法的效益。

翻譯人

本摘要由臺灣大學附設醫院郭耀文翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

為照護老人的健康照護機構工作人員施打疫苗, 目前仍無確切的數據指出健康照護機構工作人員得到經實驗方法確診的流感的發生率為多少 這篇綜合性評論初版的3篇研究,及更新版的2篇研究, 都有偏差的高度風險 這些研究發現為照護長照機構中老人的健康照護機構工作人員施打疫苗, 對於關注的特定後果並沒有效益, 包括經實驗方法確診的流感、肺炎、及肺炎造成的死亡, 但和流感無直接關連性的非特定後果卻有效益: 包括類流感疾病(可由許多其他病毒或細菌引起), 尋求家庭醫師協助的比例,住院率,及60歲以上老人的總死亡率(冬季流行的流感造成60歲以上老人的死亡,占總死亡率不到10%, 因此總死亡率的改變,可能是有其他原因造成) 健康照護機構工作人員接種疫苗的比例少於老年居民, 調查指出沒有接種的原因包括他們不認為他們具有風險、懷疑疫苗的效果、擔心疫苗的副作用、沒有意識到他們照顧的病人具有風險。 除了為健康照護機構工作人員施打疫苗外, 這篇綜合性評論並沒有找到可共同介入的做法, 如洗手,戴口罩,利用鼻黏膜拭子早期確診流感, 在流行期隔離樓層居民或整個長照機構, 避免新居民入住, 立即抗病毒藥物使用, 及要求健康照護機構工作人員出現類流感症狀時不要上班 我們的結論是目前沒有證據指出為健康照護機構工作人員施打疫苗可減少長照機構的老年居民得到流行性感冒、肺炎、或肺炎造成的死亡;而整合其他的介入性作法(包括洗手,戴口罩,利用鼻黏膜拭子早期確診流感, 抗病毒藥物使用、隔離居民、限制訪客、要求健康照護機構工作人員出現類流感症狀時不要上班)是否能保護長照機構內60歲以上的居民, 則需要高品質的隨機對照臨床試驗來證實

Résumé scientifique

Vaccination antigrippale pour les travailleurs de la santé travaillant avec des personnes âgées

Contexte

Les taux de grippe chez les travailleurs de la santé (TDS) ne sont pas connus mais pourraient être similaires à ceux de la population générale, ce qui implique un risque de transmission de la grippe à leurs patients.

Objectifs

Identifier les études examinant la vaccination des TDS et l'incidence de la grippe, de ses complications et du syndrome grippal (SG) chez les individus de ≥ 60 ans résidant dans des établissements de soins de longue durée (ESLD).

Stratégie de recherche documentaire

Nous avons consulté CENTRAL (Bibliothèque Cochrane 2009, numéro 3), qui contient le registre spécialisé du groupe Cochrane sur les infections respiratoires aiguës, ainsi que MEDLINE (1966 à 2009), EMBASE (1974 à 2009), Biological Abstracts et Science Citation Index-Expanded.

Critères de sélection

Les essais contrôlés randomisés (ECR) et les non ECR portant sur une vaccination antigrippale chez des TDS travaillant avec des individus de ≥ 60 ans dans des ESLD et examinant l'incidence de la grippe confirmée en laboratoire, de ses complications ou du SG.

Recueil et analyse des données

Deux auteurs ont, de manière indépendante, extrait les données et évalué le risque de biais.

Résultats principaux

Nous avons identifié quatre ECR en cluster (ECR-C) (n = 7 558) et une étude de cohorte (n = 12 742) portant sur une vaccination antigrippale chez des TDS travaillant avec des individus de ≥ 60 ans dans des ESLD. Les données combinées de ces trois ECR-C ne révélaient aucun effet sur les critères de jugement spécifiques : la grippe confirmée en laboratoire, la pneumonie ou les décès par pneumonie. Pour les critères de jugement non spécifiques, les données combinées de trois ECR-C indiquaient que la vaccination des TDS réduisait le SG ; les données issues d'un ECR-C indiquaient que la vaccination des TDS réduisait les consultations médicales pour cause de SG ; et les données combinées de trois ECR-C montraient une réduction de la mortalité toutes causes confondues chez les individus de ≥ 60 ans.

Conclusions des auteurs

Aucun effet n'était observé concernant les critères de jugement spécifiques : la grippe confirmée en laboratoire, la pneumonie et les décès par pneumonie. Un effet était observé sur les critères de jugement non spécifiques du SG, des consultations médicales pour cause de SG et de la mortalité toutes causes confondues chez les individus de ≥ 60 ans. Ces critères de jugement non spécifiques sont difficiles à interpréter car le SG inclut de nombreux agents pathogènes et que la grippe hivernale représente moins de 10 % de la mortalité toutes causes confondues chez les individus de ≥ 60 ans. Les critères les plus importants sont la prévention de la grippe confirmée en laboratoire chez les individus de ≥ 60 ans, de la pneumonie et des décès par pneumonie, et nous ne sommes pas en mesure de tirer de conclusions en la matière.

Les études identifiées présentent un risque de biais élevé.

Certains TDS ne se font pas vacciner parce qu'ils ne perçoivent pas de risque, doutent de l'efficacité du vaccin et sont préoccupés par les effets secondaires. Cette revue n'a identifié aucune information concernant d'autres co-interventions en plus de la vaccination des TDS : le lavage des mains, le port de masques faciaux, la détection précoce de la grippe confirmée en laboratoire, la quarantaine, le report des admissions, les antiviraux et la non-présentation à leur poste de travail des TDS atteints de SG. Nous en concluons qu'aucune preuve n'indique que la vaccination des TDS permet de prévenir la grippe chez les résidents âgés des ESLD. Des ECR de haute qualité sont nécessaires afin d'éviter tout risque de biais méthodologique et de réalisation et d'examiner des combinaisons de ces interventions.

Plain language summary

Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions

Older individuals in long-term care institutions (LTCIs) at risk of influenza may be infected by their healthcare workers. There are no accurate data on rates of laboratory-proven influenza in healthcare workers. Vaccinating healthcare workers against influenza may reduce infections acquired from this source. Because the signs and symptoms of influenza are similar to those of many other respiratory illnesses, it is important in studies testing the effects of influenza vaccination to prove by laboratory tests which are highly accurate whether residents in LTCIs actually have influenza or another respiratory illness.

Three randomised controlled trials (RCTs) (5896 participants) provided outcome data meeting our criteria. For risk of bias: randomisation was at low risk in two trials and unclear in one; allocation concealment and blinding in all three trials was unclear; incomplete outcome data in one trial was at low risk and in two at high risk; selective reporting all three trials was at low risk; performance bias (incomplete influenza vaccination of healthcare workers in the intervention arms) in all three trials was at high risk. No studies reported on adverse events. Vaccinating healthcare workers who care for those aged 60 or over in LTCIs showed no effect on laboratory-proven influenza or complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract illness) in those aged 60 or over resident in LTCIs.

This review did not find information on other interventions used in conjunction with vaccinating healthcare workers (hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding new admissions, prompt use of antivirals and asking healthcare workers with an influenza-like illness not to work.

There is no evidence that only vaccinating healthcare workers prevents laboratory-proven influenza or its complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 or over in LTCIs and thus no evidence to mandate compulsory vaccination of healthcare workers. Other interventions, such as hand-washing, masks, early detection of influenza with nasal swabs, antivirals, quarantine, restricting visitors and asking healthcare workers with an influenza-like illness not to attend work, might protect individuals over 60 in LTCIs. High-quality randomised controlled trials testing combinations of these interventions are needed.

Résumé simplifié

Vaccination antigrippale pour les travailleurs de la santé travaillant avec des personnes âgées

Il n'existe aucune donnée précise concernant le taux de grippe confirmée en laboratoire chez les travailleurs de la santé.

Les trois études incluses dans la première version de cette revue et les deux nouvelles études identifiées lors de cette mise à jour présentent toutes un risque de biais élevé.

Ces études indiquaient que la vaccination des travailleurs de la santé s'occupant de personnes âgées dans des établissements de soins de longue durée n'avait aucun effet sur les critères de jugement spécifiques examinés, à savoir la grippe confirmée en laboratoire, la pneumonie ou les décès par pneumonie. Un effet était observé sur des critères de jugement indirectement liés à la grippe, à savoir le syndrome grippal (qui implique de nombreux autres virus et bactéries en plus de la grippe), les consultations médicales pour cause de syndrome grippal, les hospitalisations et la mortalité globale chez les personnes âgées (la grippe hivernale est responsable de moins de 10 % des décès chez les personnes de plus de 60 ans, et la mortalité globale est donc due à de nombreuses autres causes).

Les taux de vaccination antigrippale sont plus faibles chez les travailleurs de la santé que chez les personnes âgées, et les enquêtes montrent que les travailleurs de la santé qui ne se font pas vacciner ne se considèrent pas à risque, doutent de l'efficacité du vaccin antigrippal, sont préoccupés par les effets secondaires et, pour certains, ne perçoivent pas leurs patients comme des sujets à risque. Cette revue n'a identifié aucune information concernant d'autres interventions pouvant être utilisées conjointement avec la vaccination des travailleurs de la santé, par exemple le lavage des mains, le port de masques faciaux, la détection précoce de la grippe confirmée en laboratoire au moyen d'écouvillons nasaux chez les individus atteints de syndrome grippal, la mise en quarantaine des sols et de l'ensemble des établissements de soins de longue durée lors d'une épidémie, le report des nouvelles admissions, l'utilisation rapide d'antiviraux et la non-présentation à leur poste de travail des travailleurs de la santé atteints de syndrome grippal.

Nous en concluons qu'aucune preuve ne permet d'affirmer que la seule vaccination des travailleurs de la santé permet de prévenir la grippe confirmée en laboratoire, la pneumonie et les décès par pneumonie chez les résidents âgés des établissements de soins de longue durée. D'autres interventions telles que le lavage des mains, le port de masques, la détection précoce de la grippe au moyen d'écouvillons nasaux, l'utilisation d'antiviraux, la quarantaine, la restriction des visites et la non-présentation à leur poste de travail des travailleurs de la santé atteints de syndrome grippal pourraient protéger les personnes de plus de 60 ans résidant dans des établissements de soins de longue durée, et des essais contrôlés randomisés de haute qualité examinant des combinaisons de ces interventions sont nécessaires.

Notes de traduction

Traduit par: French Cochrane Centre 1st December, 2012
Traduction financée par: Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux

Laienverständliche Zusammenfassung

Grippeimpfung für Pflegepersonal, das in Langzeitpflegeeinrichtungen lebende Personen im Alter von 60 Jahren und älter pflegt

In Langzeitpflegeeinrichtungen lebende ältere Menschen mit Gripperisiko können vom Pflegepersonal angesteckt werden. Es gibt keine genauen Daten zur Häufigkeit von im Labor nachgewiesener Grippe bei Pflegepersonal. Die Impfung von Pflegepersonal gegen Grippe könnte die Anzahl der von ihm ausgehenden Ansteckungen reduzieren. Da die Anzeichen und Symptome von Grippe denen vieler anderer Atemwegserkrankungen ähneln, ist es in Studien, die die Wirkung von Grippeimpfungen testen, wichtig, in sehr genauen Labortest zu prüfen, ob die Bewohner von Langzeitpflegeeinrichtungen tatsächlich an einer Grippe erkranken oder einer anderen Atemwegserkrankung.

Drei randomisierte kontrollierte Studien (RCT) (5896 Teilnehmer) lieferten Ergebnisdaten, die unseren Kriterien entsprachen. Risiko für Bias: Die Randomisierung wies ein geringes Risiko in zwei Studien auf und war in einer unklar; die verborgene Zuordnung und Verblindung waren in allen drei Studien unklar; das Risiko für unvollständige Ergebnisdaten war in einer Studie gering und in zweien hoch; das Risiko für selektive Berichterstattung war in allen drei Studien gering; das Risiko für Performance-Bias (unvollständige Grippeimpfung des Gesundheitspersonals in den Interventions-Studiengruppen) war in allen drei Studien hoch. Keine der Studien berichtete über unerwünschte Ereignisse. Die Impfung von Pflegepersonal, das sich um Personen im Alter von 60 Jahren und älter in Langzeitpflegeeinrichtungen kümmert, zeigte keine Wirkung auf im Labor nachgewiesene Grippefälle oder Komplikationen (Infektion der unteren Atemwege, Krankenhauseinweisung oder Tod aufgrund einer Erkrankung der unteren Atemwege) bei in Langzeitpflegeeinrichtungen lebenden Personen im Alter von 60 Jahren und älter.

In diesem Review wurden keine Angaben zu anderen Interventionen gefunden, die in Verbindung mit der Impfung des Pflegepersonals angewendet wurden (Händewaschen, Mundschutz, Früherkennung von im Labor nachgewiesener Grippe, Quarantäne, Vermeidung von Neuaufnahmen, sofortige Anwendung von Virostatika und die Aufforderung an Pflegepersonal mit grippeähnlichen Erkrankungen, nicht zur Arbeit zu kommen).

Es gibt keine Evidenz dafür, dass die Impfung von Pflegepersonal allein gegen im Labor nachgewiesene Grippe oder damit einhergehende Komplikationen (Infektion der unteren Atemwege, Einweisung ins Krankenhaus oder Tod infolge einer Infektion der unteren Atemwege) bei Personen im Alter von 60 Jahren und älter in Langzeitpflegeeinrichtungen vorbeugt, und damit auch keine Evidenz dafür, die freiwillige Impfung von Pflegepersonal zur Pflicht zu machen. Andere Interventionen, wie Händewaschen, Mundschutz, Früherkennung von Grippe durch Nasenabstrich, Virostatika, Quarantäne, Besuchseinschränkung und Aufforderung an die Gesundheitsfachleute mit grippeähnlichen Erkrankungen, nicht zur Arbeit zu kommen, könnten Personen über 60 in Langzeitpflegeeinrichtungen vielleicht schützen. Es besteht Bedarf an hochwertigen randomisierten kontrollierten Studien, die Kombinationen dieser Interventionen untersuchen.

Anmerkungen zur Übersetzung

Koordination durch Cochrane Schweiz

Background

Description of the condition

Healthcare workers, such as doctors, nurses, other health professionals, cleaners and porters (and also family visitors), may have substantial rates of clinical and sub-clinical influenza during influenza seasons (Elder 1996; Ruel 2002) but there are no reliable data on rates of laboratory-proven influenza in healthcare workers and whether they differ from those of the general population (Jefferson 2009). Laboratory-proven influenza in the general population on average accounts for a small proportion of 'influenza-like illnesses'. Data from the control arms of randomised controlled trials (RCTs) could provide data on laboratory-proven influenza rates.

Healthcare workers often continue to work when infected with influenza, increasing the likelihood of transmitting influenza to those in their care (Coles 1992; Weingarten 1989; Yassi 1993). Those aged 60 or older in institutions such as long-stay hospital wards and nursing homes are at risk of influenza and its complications, especially if affected with multiple pathologies (Fune 1999; Jackson 1992; Muder 1998; Nicolle 1984).

Description of the intervention

One way to prevent the spread of influenza to those aged 60 years or older resident in long-term care institutions (LTCIs) may be to vaccinate healthcare workers. The Centers for Disease Control (CDC) Advisory Committee on Immunisation Practices (ACIP) recommends vaccination of all healthcare workers (Harper 2004). However, only 36% of healthcare workers in the US were vaccinated in 2003 (CDC 2003), 35% of staff in LTCIs in Canada were vaccinated in 1999 (Stevenson 2001) and 34% to 44% after a randomised controlled trial (RCT) in 43 geriatric healthcare settings in France to increase vaccination rates (Rothan-Tondeur 2010). Nurses and (in some institutions) physicians, tend to have lower influenza vaccination rates than other healthcare workers. This relatively low uptake may partly be a reflection of doubts as to the vaccine's efficacy (its ability to prevent influenza) (Ballada 1994; Campos 2002-3; Ludwig-Beymer 2002; Martinello 2003; Quereshi 2004). The design and execution of campaigns to increase vaccination rates are also important (Doebbeling 1997; NFID 2004; Russell 2003a; Russell 2003b), in order to provide an intervention at minimal risk of bias from inadequate randomisation, concealment of allocation, blinding, attrition, incomplete reporting and inappropriate statistical analysis.

How the intervention might work

Healthcare workers are the key group who enter nursing and LTCIs on a daily basis. Immune systems of the elderly are less responsive to vaccination and vaccinating healthcare workers could reduce the exposure of those aged 60 years or older to influenza.

Why it is important to do this review

Previous systematic reviews of the effects of influenza vaccines in those aged 60 years or older are now out of date or do not include all relevant studies. The Gross 1995 review is 17 years old and its conclusions are affected by the exclusion of recent evidence. The Vu 2002 review has methodological weaknesses (excluding studies with denominators smaller than 30 and quantitative pooling of studies with different designs), which are likely to undermine the conclusions. A systematic review by Jordan 2004 of the effects of vaccinating healthcare workers against influenza on high-risk individual elderly reports significantly lower mortality in the elderly (13.6% versus 22.4%, odds ratio (OR) 0.58, 95% confidence interval (CI) 0.4 to 0.84) but does not include the latest studies. The Burls 2006 systematic review of effects on elderly people only identified the RCTs by Potter 1997 and Carman 2000, and Anikeeva 2009 does not include the study by Lemaitre 2009. It is important to provide accurate information for policy makers and highlight the need for high-quality trials to test combinations of interventions, including healthcare worker vaccination.

There are Cochrane systematic reviews assessing the effects of influenza vaccines in children (Jefferson 2012), the elderly (Jefferson 2010b), healthy adults (Jefferson 2010a), people affected with chronic obstructive pulmonary disease (Poole 2010) and cystic fibrosis (Dharmaraj 2009).

Objectives

To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older residing in LTCIs.

Methods

Criteria for considering studies for this review

Types of studies

RCTs and non-RCTs (cohort or case-control studies) reporting exposure and outcomes by vaccine status.

Types of participants

Healthcare workers (nurses, doctors, nursing and medical students, other health professionals, cleaners, porters and volunteers who have regular contact with those aged 60 years or older) of all ages, caring for those aged 60 years or older in institutions such as nursing homes, LTCIs or hospital wards.

Types of interventions

Vaccination of healthcare workers with any influenza vaccine given alone or with other vaccines, in any dose, preparation, or time schedule, compared with placebo or with no intervention. Studies on vaccinated elderly are included in reviews looking at the effects of influenza vaccines in the elderly (Jefferson 2010b). The Jefferson 2010a review looked at the effects of vaccination in healthy adults such as healthcare workers.

Types of outcome measures

Primary outcomes

Outcomes in those aged 60 years or older in LTCIs.

  1. Cases of influenza in those aged 60 years or older confirmed by viral isolation or serological supporting evidence (or both), plus a list of likely respiratory symptoms.

  2. Lower respiratory tract infection.

  3. Admission to hospital for respiratory illness.

  4. Deaths caused by respiratory illness.

We excluded studies reporting only serological outcomes in the absence of symptoms. Outcomes for healthcare workers were not considered.

Secondary outcomes

We did not select any secondary outcomes. We did not choose influenza-like illness (ILI) (Appendix 1) or all-cause mortality (Appendix 2) because these are not the effects the vaccines were produced to address. Influenza vaccines were designed and produced to prevent a specific disease caused by two specific viruses, not a syndrome such as ILI which includes a wide variety of viruses and studies of such cases often cannot document a specific cause of infection. ILI may be useful to some health officials for rough estimates of upcoming workload during the viral season. We did not use all-cause mortality because of deficiencies in laboratory-proven ascertainment of cause of death due to influenza, and thus under-reporting of influenza on death certificates.

Search methods for identification of studies

Electronic searches

For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 2, part of The Cochrane Library, www.thecochranelibrary.com (accessed 28 March 2013) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (September 2009 to March week 3, 2013), EMBASE (September 2009 to March 2013) and Web of Science (2009 to March 2013). See Appendix 3 for details of previous searches. There were no language restrictions.

We searched MEDLINE and CENTRAL using the following search strategy. We combined the MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity-maximising version (2008 revision); Ovid format (Lefebvre 2011). We adapted the search strategy to search EMBASE (Appendix 4) and Web of Science (Appendix 5).

We also combined the following search strategy with the SIGN filter (SIGN 2009) for identifying observational studies and ran the searches in MEDLINE and adapted them for EMBASE and Web of Science (see Appendix 6).

MEDLINE (Ovid)

1 Influenza Vaccines/
2 Influenza, Human/
3 exp Influenzavirus A/
4 exp Influenzavirus B/
5 influenza.tw.
6 flu.tw.
7 or/2-6
8 exp Vaccines/
9 Vaccination/
10 vaccin*.tw,nm.
11 exp Immunization/
12 (immuniz* or immunis*).tw.
13 or/8-12
14 7 and 13
15 1 or 14
16 exp Health Personnel/
17 ((health or health care or healthcare) adj2 (personnel or worker* or provider* or employee* or staff or professional*)).tw.
18 ((medical or hospital) adj2 (staff or employee* or personnel or worker*)).tw.
19 (doctor* or physician* or clinician*).tw.
20 (allied health adj2 (staff or personnel or worker*)).tw.
21 paramedic*.tw.
22 nurse*.tw.
23 (nursing adj2 (staff or personnel or auxiliar*)).tw.
24 exp Hospitals/
25 Long-Term Care/
26 exp Residential Facilities/
27 Health Services for the Aged/
28 nursing home*.tw.
29 (institution* adj3 elderly).tw.
30 aged care.tw.
31 hospice*.tw.
32 ((long stay or long term) adj3 (ward* or facilit* or hospital*)).tw.
33 old people* home*.tw.
34 Geriatrics/
35 geriatric*.tw.
36 or/16-35
37 15 and 36

Searching other resources

We searched the WHO International Clinical Trials Registry Platform (ICTRP) and US National Institutes of Health trials registry (latest search 2 November 2012). We also searched the Database of Abstracts of Reviews of Effects (DARE) 2013 part of The Cochrane Library and reviewed the references for further possible studies. We searched bibliographies of retrieved articles and contacted trial authors for further details, if required.

Data collection and analysis

Selection of studies

Two review authors (TJL, RET) independently reviewed the abstracts by using the following inclusion criteria.

  1. People 60 years or older.

  2. LTCIs or hospitals.

  3. Healthcare workers.

  4. Influenza vaccination.

  5. Morbidity and mortality of residents.

Disagreements were resolved by a third review author (TOJ).

Data extraction and management

Two review authors (RET, TJL) applied the inclusion criteria to all identified and retrieved articles and extracted data from included studies into standard Cochrane Vaccines Field forms. We extracted the following data in duplicate.

  • Methods: purpose; design; period study conducted and statistics.

  • Participants: country or countries of study; setting; eligible participants; age and gender.

  • Interventions and exposure: in intervention group and control group.

  • Outcomes in those aged 60 years or older residing in LTCIs:

  1. Cases of influenza confirmed by viral isolation or serological supporting evidence (or both) plus a list of likely respiratory symptoms.

  2. Lower respiratory tract infection.

  3. Hospitalisation for respiratory illness.

  4. Death from respiratory illness.

Two review authors (RET, TJL) independently checked data extraction and disagreements were resolved by third review author (TOJ).

Assessment of risk of bias in included studies

We carried out assessment of methodological quality for RCTs using The Cochrane Collaboration's 'Risk of bias' tool (Higgins 2011). We assessed the quality of non-RCTs in relation to the presence of potential confounders using the appropriate Newcastle-Ottawa Scales (NOS) (Wells 2005). The NOS asks whether all possible precautions against confounding have been taken by the study designers and links study quality to the answer. We translated the number of inadequately reported or conducted items into categories of risk of bias. We used quality at the analysis stage as a means of interpreting the results. The review authors resolved disagreements on inclusion or methodological quality of studies by discussion. Two review authors (RET, TOJ) checked quality assessment.

We looked for details of formal ethics approval and informed consent of participants.

Measures of treatment effect

We assessed efficacy against laboratory-proven influenza, pneumonia, deaths from pneumonia and hospitalisation using risk differences (RD) with 95% confidence intervals (CI). The number needed to vaccinate (NNV) was computed as 1/RD.

Unit of analysis issues

All three RCTs that provided outcome data that met our criteria were cluster-RCTs. Carman 2000 did not control for clustering and we were not able to adjust his data to do so. We adjusted the precision of the study estimates for the cluster-RCTs based on standard Cochrane Handbook for Systematic Reviews of Interventions advice (Higgins 2011). We contacted trial authors to ascertain the intra-cluster correlation coefficient (ICC) and to confirm statistical analyses.

Dealing with missing data

We did not use any strategies to impute missing outcome data and recorded missing data in the 'Risk of bias' table. We attributed an ICC to two studies (Carman 2000; Potter 1997) from an assumed intra-cluster variance of 2.3% from a larger study we did not include (Hayward 2006).

Assessment of heterogeneity

We used the Chi2 test and I2 statistic to assess heterogeneity and pooled studies in meta-analysis only if the I2 statistic was less than approximately 50%.

Assessment of reporting biases

We reviewed an additional 554 abstracts for potential RCTs and 251 for non-RCTs and 312 citations from the systematic review by Jefferson 2010b. We identified only three cluster-RCTs that met our criteria for outcome data and so we could not create a funnel plot to assess publication bias due to the small number of included studies.

Data synthesis

We meta-analysed RCTs when the I2 statistic was less than approximately 50% and used the random-effects model as it could not be assumed that the studies came from similar populations.

Subgroup analysis and investigation of heterogeneity

Whenever data presented in the study allowed it, we carried out subgroup analysis according to the vaccination status of residents aged 60 years or older. We assessed the following outcomes which arose during the influenza season.

  1. Laboratory-proven influenza infections (by paired serology, nasal swabs, reverse-transcriptase polymerase chain reaction (RT-PCR) or tissue culture).

  2. Lower respiratory tract infection.

  3. Hospitalisation for respiratory illness.

  4. Death from respiratory tract illness.

Sensitivity analysis

With only three cluster-RCTs that met our criteria for outcome data, a sensitivity analysis was not feasible.

Results

Description of studies

Results of the search

This updated 2013 search retrieved 268 records with the RCT filter and 479 records with the observational filter.

The 2009 search had retrieved a total of 554 records in the search for RCTs and 251 records in the search for observational studies and in the first publication of this review we also examined 312 reports for detailed assessment from the review on the effects of influenza vaccines in the elderly (Jefferson 2010b). Due to the comprehensive nature of the Cochrane review on the effects of influenza vaccines in the elderly (Jefferson 2010b) we carried out a review with a very focused study question and benefited from extensive searches which generated a large number of 'hits' but a relatively low yield of studies to include.

We found three cluster-RCTs that met our criteria for outcome data. For the third publication of this review we have excluded outcome data relating to influenza-like illness (Appendix 1) and all-cause mortality (Appendix 2) as outcome measures. Two studies that were in the second publication no longer contribute outcome data to this review: one cluster-RCT (Hayward 2006) as the main outcome measure was all-cause mortality and the secondary measure was ILI; and a cohort study (Oshitani 2000) which used ILI as the outcome measure.

Included studies

Five studies met the inclusion criteria (see Characteristics of included studies table). Three studies contribute data to the outcomes of interest to this review, recruiting a total of (5896 participants) (Carman 2000; Lemaitre 2009; Potter 1997). These three studies were comparable in study populations, intervention and outcome measures. The studies did not report on adverse events.

Excluded studies

All 747 new citations identified in the 2013 search for this third publication of this review were excluded because they either did not have influenza vaccination outcome data for those aged 60 years or older or healthcare workers, or both, or did not report the outcome data we specified, or reported only influenza antibody levels.

Risk of bias in included studies

See the 'Risk of bias' tables and Figure 1 and Figure 2.

Figure 1.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Allocation

There was adequate sequence generation in three studies. One used a random-number table (Carman 2000) and one used a centralised random-number generator (Lemaitre 2009), and for the third study we considered that the process was likely to have been carried out reliably (Hayward 2006). However, there was uncertainty in one study (Potter 1997): "Hospital sites were stratified by unit policy for vaccination, then randomised for their healthcare workers to be routinely offered either influenza vaccination and patients unvaccinated...".

Blinding

No RCTs explicitly stated that they had appropriate means of blinding participants or study personnel to vaccination. In Carman 2000 and Potter 1997 there is no statement that any researcher, assessor, data analyst, healthcare worker or participant was blinded. In Carman 2000 the study nurses "took additional opportunistic nose and throat swabs from non-randomised patients who the ward nurses thought had an influenza-like illness". In Potter 1997 ward nurses paged the research nurses "if any patients under their care developed clinical symptoms suggestive of upper respiratory tract viral illness, influenza, or lower respiratory tract infection," and in Lemaitre 2009 "Influenza vaccination was further recommended during face-to-face interviews with each member of staff ... The study team individually met all administrative staff, technicians and caregivers to invite them to participate and volunteers were vaccinated at the end of the interview."

Incomplete outcome data

Incomplete data were not addressed in three studies (Carman 2000; Hayward 2006; Potter 1997).

Selective reporting

No study appeared to report results selectively.

Other potential sources of bias

For Potter 1997 potential sources of bias were as follows.

  1. Selection bias: the total number of long-term care hospitals in West and Central Scotland is not stated. There were inconsistencies in outcome gradients (Table 1). In the population under observation, Potter 1997 reported 216 cases of suspected viral illness, 64 cases of influenza-like illness, 55 cases of pneumonia, 72 deaths from pneumonia and 148 deaths from all causes; in the sub-population of both vaccinated staff and patients, Potter 1997 reported 24 cases of suspected viral illness, two cases of influenza-like illness, seven cases of pneumonia, 10 deaths from pneumonia and 25 deaths from all causes. As these gradients are not plausible (one would expect a greater proportion of cases of influenza-like illness to be caused by influenza during a period of high viral activity), the effect on all-cause mortality is likely to reflect a selection bias rather than a real effect of vaccination.

    Table 1. Potter 1997
    1. S0P0: staff and patients not vaccinated
      S0PV: staff not vaccinated, patients vaccinated
      SVPV: staff and patients vaccinated
      SVP0: staff vaccinated and patients not vaccinated

     SVPVSVP0S0PVS0P0
    Suspected viral illness24587559
    Influenza-like illness2201923
    Pneumonia7141618
    Deaths from pneumonia10152423
    All deaths25255642
  2. Performance bias: 67% of staff in active arm one and 43% in active arm two were vaccinated.

  3. There is no description of the vaccines administered, vaccine matching or background influenza epidemiology.

For Carman 2000 potential sources of bias were as follows.

  1. Selection bias: the total number of long-term care hospitals in West and Central Scotland is not stated. In the long-term care hospitals in which healthcare workers were offered vaccination, residents had higher Barthel scores.

  2. Performance bias: only 51% of healthcare workers in the Lemaitre 2009 arm received vaccine in the long-term care hospitals where vaccine was offered and 4.8% where it was not; 48% of patients received vaccine in the arm where healthcare workers were offered vaccination and 33% in the arm where healthcare workers were not.

  3. Statistical bias: the analysis was not corrected for clustering, unlike the Potter 1997 pilot; in the long-term care hospitals where healthcare workers were offered vaccination, the patients had significantly higher Barthel scores and were more likely to receive influenza vaccine (no significance level stated) and due to missing data these differences could not be adjusted for other than by estimation. Statistical power may also have been a problem as the detection rate of 6.7% was lower than the estimated rate of 25% used in the power calculation.

The Potter 1997 and Carman 2000 cluster-RCTs can be regarded as investigations in the same geographical area with a modest possible but unknown overlap of staff and residents. Only three of the long-term care hospitals in the Potter 1997 study were included in the Carman 2000 cluster-RCT because some of the homes were closed down (e-mail communication from Dr. Stott) but the continuity of staff between the institutions is unknown.

Ethics approval: Carman 2000, Lemaitre 2009 and Potter 1997 received formal ethics approval. Carman 2000 and Potter 1997 obtained written informed consent from healthcare workers and witnessed verbal consent from participants for nose swabs to be taken and Potter 1997 for blood samples. The LTCIs already had policies for opting in or opting out of influenza vaccination. Lemaitre 2009 obtained face-to-face informed consent from healthcare workers.

Effects of interventions

Primary outcomes

1. Cases of influenza in those aged 60 years or older confirmed by viral isolation or serological supporting evidence (or both), plus a list of likely respiratory symptoms

Potter 1997 reported outcomes only for unvaccinated patients. We computed a risk difference (RD) of 0.01, 95% confidence interval (CI) -0.03 to 0.05, P = 0.73). Carman 2000 reported data on influenza cases among vaccinated and unvaccinated patients combined. We computed a RD of -0.01, 95% CI -0.05 to 0.03, P = 0.54). We were able to pool the results for Carman 2000 and Potter 1997 and we computed an overall RD of -0.00, 95% CI -0.03 to 0.03, P = 0.45, I2 statistic = 0% (Analysis 1.1). The pooled RD based on adjusted study effect estimates was 0.00, 95% CI -0.03 to 0.03 (Analysis 2.1).

2. Lower respiratory tract infection

Only Potter 1997 reported data for lower respiratory tract infection. He reported results separately for vaccinated and unvaccinated patients. For vaccinated patients we computed a RD of -0.02, 95% CI -0.05 to 0.01, P = 0.21. For unvaccinated we computed a RD of -0.02, 95% CI -0.06 to 0.03, P = 0.47. For the vaccinated and unvaccinated patients combined we computed a RD of -0.02, 95% CI -0.04 to 0.01, P = 0.15, I2 statistic = 0% (Analysis 1.2).

3. Admission to hospital for respiratory illness

Only Lemaitre 2009 provided data for "admissions to hospital for respiratory illness" and we computed a RD of 0.00, 95% CI -0.02 to 0.02, P = 0.84 (Analysis 1.3). The pooled RD based on adjusted study effect estimates was RD 0.00, 95% CI -0.02 to 0.03 (Analysis 2.3).

4. Deaths caused by respiratory illness

Potter 1997 reported data for deaths from pneumonia separately for vaccinated patients and unvaccinated patients. For vaccinated patients we computed a RD of -0.03, 95% CI -0.07 to 0.01, P = 0.09 and for unvaccinated we computed a RD of -0.03, 95% CI -0.07 to 0.01, P = 0.18. Lemaitre 2009 reported results for "deaths from respiratory illness" (not further defined) for vaccinated and unvaccinated patients combined and we computed a RD of 0.00 (95% CI -0.00 to 0.01, P = 0.23) (Analysis 1.4). We computed a pooled result for Potter 1997 and Lemaitre 2009 of -0.02, 95% CI -0.06 to 0.02, P = 0.40 but the I2 statistic = 81%. Using the pooled RD based on adjusted study effect estimates was RD -0.01; 95% CI -0.05 to 0.03 (Analysis 2.4).

Discussion

We identified three cluster-RCTs which met our criteria for outcome data to answer the question of whether vaccinating healthcare workers against influenza protects those aged 60 years or older residing in LTCIs. For the three cluster-RCTs we assessed the risk of bias for sequence generation as low in two and unclear in one; concealment of allocation as unclear in all three; blinding as unclear in all three; incomplete data as low risk in one and high in two; selective reporting as low in all three and for other biases (performance bias due to incomplete influenza vaccination of the healthcare workers in the intervention arms) we assessed all three as high risk of bias. Carman 2000 did not adjust results for the effect of clustering.

Pooled data showed no effect on specific outcomes: laboratory-proven influenza (Carman 2000; Potter 1997), lower respiratory tract infections (Potter 1997), admissions to hospital for lower respiratory tract illness (Lemaitre 2009) and deaths from lower respiratory tract illness (Lemaitre 2009; Potter 1997), with the 95% CI in each case including unity.

One question is what is the maximum contribution that influenza vaccination of people aged 60 years or older could make in reducing total annual mortality? A population study by Simonsen 2006 used data from the US national multiple-cause-of-death databases from 1968 to 2001 and found that for those aged 65 years or older, the mortality attributable to pneumonia or influenza never exceeded 10% of all deaths during those winters. The study by Vila-Córcoles 2007 of 11,240 Spanish community-dwelling elderly, conducted between January 2002 and April 2005, found the attributable mortality risk in individuals not vaccinated against influenza was 24 deaths/100,000 person-weeks within influenza periods. Vaccination prevented 14% of these deaths for the population and one death was prevented for every 239 annual vaccinations (ranging from 144 in winter 2005 to 1748 in winter 2002). It should be noted that these data are not for residents of LTCIs. A mathematical model predicted that for a 30-bed unit, an increase in healthcare worker vaccination rates from 0% to 100% would decrease resident influenza infections by 60% (van den Dool 2008).

Summary of main results

We identified three cluster-RCTs that provided outcome data that met our criteria. Pooled data showed that there was no effect on laboratory-proven influenza, lower respiratory tract infections, admissions to hospital for respiratory illness or deaths from respiratory illness.

Overall completeness and applicability of evidence

Three cluster-RCTs focused directly on the question of the effect of healthcare worker vaccination on the mortality and morbidity of long-term care facility residents aged 60 years or older. The three cluster-RCTs contributed data from a total of 5896 residents in LTCIs. These three (and Hayward 2006) cluster RCTs have certain common features: they are all underpowered to detect any difference in influenza mortality which is a rare event. All participants, were they residents or carers, were unblinded to their intervention status. All trials showed no reduction in influenza or its complications (the registered indication for the vaccines), and all reached conclusions which were not based on the data presented. As influenza is not even in the top 10 causes of death in the elderly, none of the trialists seemed to reflect on the sheer implausibility of no effect on influenza but apparent effect on a syndrome (ILI) which is caused only in part by influenza viruses.

Quality of the evidence

The estimated effects for the outcomes we assessed in this review are imprecise and we considered the studies that contributed outcome data to have been at a high risk of bias. The analysis of both adjusted and unadjusted study results for the four outcomes of interest were consistent with each other. The high I2 statistic observed for the outcome of influenza-related mortality (81%) was lower after adjustment for the design effect (49%), without any substantive change in the pooled result. The absence of usable outcome data for the specific effects of healthcare worker vaccination programmes from Hayward 2006 and Oshitani 2000 restricts the applicability of our findings further.

Potential biases in the review process

We imposed no language restrictions on the search and all studies were independently assessed by two review authors. The intra-cluster correlation coefficients (ICCs) we used for one of the studies were based on the estimate provided by Hayward 2006. Although the recalculation of the effective sample size was done in accordance with recommended procedures (Higgins 2011), we have assumed that the adjustment required is the same across the outcomes extracted for each study. Rather than increase uncertainty around the pooled effect size, adjustment of the standard errors for the studies by our method reduced the statistical heterogeneity between the study effect estimates. If the ICCs we used as the basis for these calculations were too large, our adjusted analyses may underestimate the true amount of variation between the study results.

Agreements and disagreements with other studies or reviews

Other reviews addressing similar study questions do not include all the studies that we found.

Authors' conclusions

Implications for practice

All three cluster-randomised controlled trials (RCTs) contributing outcome data to our review are at high risk of bias and pooled data found no effect on the outcomes of direct interest, namely laboratory-proven influenza, lower respiratory tract infections and admissions to hospital and deaths from lower respiratory fract illness, with the 95% confidence interval (CI) in each case including unity. We conclude that there is an absence of high-quality evidence that vaccinating healthcare workers against influenza protects people aged 60 years or older in their care and thus there is little evidence to justify medical care and public health practitioners mandating influenza vaccination for healthcare workers who care for the elderly in long-term care institutions (LTCIs).

Implications for research

There are currently only three cluster-RCTS which provide outcome data that meet our criteria to evaluate the impact on residents aged 60 years or older of vaccinating their healthcare workers against influenza. All of these studies are at high risk of bias. RCTs are needed with minimal risk of bias from sequence generation, failure to conceal allocation, performance, attrition and detection and these should be adequately powered for the key outcomes of laboratory-proven influenza, hospitalisation for pneumonia and death from pneumonia. They should carefully define and measure outcomes including laboratory-proven influenza, lower respiratory tract infection, cause of hospitalisation and deaths from pneumonia. They should carefully consider the degree to which they must, to adequately assess outcomes, obtain proof of diagnosis for all participants by laboratory testing all participants with appropriate symptoms for influenza and all other likely viruses, performing blood cultures, white blood cell counts and other laboratory investigations and chest X-rays if pneumonia is suspected, and following the course of all hospitalised patients by scrutinising individual records so that they can definitively assess all outcomes and co-morbidities. A particular issue in the analysis of data from studies with a cluster design is the provision and use of an ICC. It is a major limitation with the analysis of data in our review that we have not had available a reliable estimate of this quantity for each of the outcomes of interest.

The area of interest is those aged 60 years or older in LTCIs. Therefore, if the existing LTCIs' organisational structure is to be used to implement the interventions, these will need to be given to clusters of residents aged 60 years or older and healthcare workers, which will make blinding difficult. An important ethical issue is informed consent by those aged 60 years or older and healthcare workers. It is not ethical to blind participants or healthcare workers but the researchers, data assessors and statisticians could all be blinded.

The elderly are much keener to be vaccinated than healthcare workers and there is extensive literature about the group of healthcare workers who say they do not feel vulnerable to influenza, do not believe the vaccine is effective and are afraid of side effects, and some of these do not perceive risk for their patients. Persistence of these beliefs may limit uptake by healthcare workers and make it difficult to test conclusively the effect of very high levels of healthcare worker influenza vaccination.

A large publicly funded trial is needed to test combinations of interventions to reduce influenza and mortality from influenza in those aged 60 years or older in LTCIs with thorough delivery of each intervention: vaccinating residents and healthcare workers, hand-washing, face masks, early detection of laboratory-proven influenza in individuals with influenza-like illness by using nasal swabs, quarantine of floors and entire LTCIs during outbreaks, avoiding new admissions, prompt use of antivirals and asking healthcare workers with an influenza-like illness not to present for work.

Acknowledgements

Professor David J. Stott, Academic Section of Geriatric Medicine, Glasgow Royal Infirmary, UK provided supplementary information on the Potter 1997 and Carman 2000 studies. Dr. Magali Lemaitre confirmed the ICC for Lemaitre 2009 and Dr. Andrew Hayward provided information regarding the analysis of data for Hayward 2006.

We acknowledge the contributions of Vittorio Demicheli (previously responsible for design of the review and responsible for the final draft of a previous version); Daniela Rivetti who was responsible for the previous searches; and Sarah Thorning, who conducted the searches for these review updates.

The authors wish to thank the following people for commenting on the draft of the second publication: Amy Zelmer, Laila Tata, Amir Shroufi, Rob Ware and John Holden.

Data and analyses

Download statistical data

Comparison 1. HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Influenza2752Risk Difference (M-H, Random, 95% CI)-0.00 [-0.03, 0.03]
1.1 Unvaccinated patients1225Risk Difference (M-H, Random, 95% CI)0.01 [-0.03, 0.05]
1.2 Vaccinated and unvaccinated patients1527Risk Difference (M-H, Random, 95% CI)-0.01 [-0.05, 0.03]
2 Lower respiratory tract infection11059Risk Difference (M-H, Random, 95% CI)-0.02 [-0.04, 0.01]
2.1 Vaccinated patients1538Risk Difference (M-H, Random, 95% CI)-0.02 [-0.05, 0.01]
2.2 Unvaccinated patients1521Risk Difference (M-H, Random, 95% CI)-0.02 [-0.06, 0.03]
3 Admission to hospital for respiratory illness13400Risk Difference (M-H, Random, 95% CI)0.00 [-0.02, 0.02]
3.1 Vaccinated and unvaccinated patients13400Risk Difference (M-H, Random, 95% CI)0.00 [-0.02, 0.02]
4 Deaths from influenza or its complications24459Risk Difference (M-H, Random, 95% CI)-0.02 [-0.06, 0.02]
4.1 Vaccinated patients1538Risk Difference (M-H, Random, 95% CI)-0.03 [-0.07, 0.01]
4.2 Unvaccinated patients1521Risk Difference (M-H, Random, 95% CI)-0.03 [-0.07, 0.01]
4.3 Vaccinated and unvaccinated patients13400Risk Difference (M-H, Random, 95% CI)0.00 [-0.00, 0.01]
Analysis 1.1.

Comparison 1 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 1 Influenza.

Analysis 1.2.

Comparison 1 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 2 Lower respiratory tract infection.

Analysis 1.3.

Comparison 1 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 3 Admission to hospital for respiratory illness.

Analysis 1.4.

Comparison 1 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 4 Deaths from influenza or its complications.

Comparison 2. HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Influenza2493Risk Difference (M-H, Random, 95% CI)0.00 [-0.03, 0.03]
1.1 Unvaccinated patients1160Risk Difference (M-H, Random, 95% CI)0.01 [-0.03, 0.05]
1.2 Vaccinated and unvaccinated patients1333Risk Difference (M-H, Random, 95% CI)-0.01 [-0.06, 0.04]
2 Pneumonia1351Risk Difference (M-H, Random, 95% CI)-0.02 [-0.06, 0.03]
2.1 Vaccinated patients1178Risk Difference (M-H, Random, 95% CI)-0.02 [-0.08, 0.03]
2.2 Unvaccinated patients1173Risk Difference (M-H, Random, 95% CI)-0.01 [-0.08, 0.06]
3 Admission to hospital for respiratory illness11789Risk Difference (M-H, Random, 95% CI)0.00 [-0.02, 0.03]
3.1 Vaccinated and unvaccinated patients11789Risk Difference (M-H, Random, 95% CI)0.00 [-0.02, 0.03]
4 Deaths from influenza or its complications22140Risk Difference (M-H, Random, 95% CI)-0.01 [-0.05, 0.03]
4.1 Vaccinated patients1178Risk Difference (M-H, Random, 95% CI)-0.04 [-0.11, 0.03]
4.2 Unvaccinated patients1173Risk Difference (M-H, Random, 95% CI)-0.03 [-0.11, 0.04]
4.3 Vaccinated and unvaccinated patients11789Risk Difference (M-H, Random, 95% CI)0.00 [-0.00, 0.01]
Analysis 2.1.

Comparison 2 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 1 Influenza.

Analysis 2.2.

Comparison 2 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 2 Pneumonia.

Analysis 2.3.

Comparison 2 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 3 Admission to hospital for respiratory illness.

Analysis 2.4.

Comparison 2 HCWs offered vaccination versus HCWs offered no vaccination: experimental design; data for periods of high influenza activity (Carman and Potter 152; Lemaitre 118 days), Outcome 4 Deaths from influenza or its complications.

Appendices

Appendix 1. Reasons not to use influenza-like illness in assessing the effectiveness of influenza vaccines

Influenza-like illness (ILI)

There are six reasons not to use ILI as an outcome.

1. There are multiple definitions. The Centers for Disease Control and Prevention (CDC) definition is a temperature ≥ 38°C, cough or sore throat or both and the absence of a known cause other than influenza (CDC 2006). Health Canada's Flu Watch uses fever, cough and ≥ one of sore throat, arthralgia, myalgia or prostration (www.phac-aspc.gc.ca/fluwatch).

2. The percentage of ILI cases that are laboratory-proven influenza cases is low. During the 2009 H1N1p pandemic in Marseille, GPs assessed 660 patients as ILI cases: 158 were positive for A/H1N1p. Of the 502 reverse-transcriptase polymerase chain reaction (RT-PCR) influenza-negative patients 296 were randomly selected for further testing: 82 were positive for at least one other virus (58 human rhinovirus, nine parainfluenza viruses 1-4, nine human coronavirus OC43, five enterovirus, four adenovirus and two human metapneumovirus) and 204 were negative for all 18 viruses tested (Thiberville 2012). A RCT in 46 Hutterite colonies in Canada defined ILI as fever ≥ 38°C, cough, runny nose, sore throat, headaches, sinus problems, muscle ache, fatigue, ear ache and chills but only 37 (26%) of 142 tested were PCR positive (Barbara 2012). A study in India defined ILI as sudden onset of fever > 38°C or a history of sudden onset of fever in the recent past (< three days), cough or sore throat and/or rhinorrhoea and SARI (severe acute respiratory infections) as an ILI with breathlessness or difficulty in breathing/tachypnoea or clinically suspected pneumonia (in children) with increased respiratory rates. They isolated influenza from only 617 (4.43%) of 13,928 throat or nasal swabs (Chadha 2011). A study in Taiwan of 26,601 ILI cases found influenza in only 25% by viral culture or RT-PCR (Chuang 2012). 

3. There is a remarkable similarity between the symptoms of influenza A/H1N1p and human rhinovirus. Of the 660 patients in Marseille, 85% had a fever (91% H1N1p, 79% HRV), 83% had a cough (97%, 86%), 75% had ILI symptoms (89%, 74%), 65% a sore throat (65%, 69%), 93% asthenia (96%, 88%), 80% myalgia (80%, 74%), 63% rhinorrhoea (74%, 81%), 77% headache (78%, 69%), 65% chills (74%, 52%), 40% arthralgia (41%, 31%) and 35% nausea (39%, 23%) (Thiberville 2012).

4. Some studies use ILI in circular definitions resulting in unclear outcomes. The Australian Flutracking programme defined ILI as the proportion of participants in their programme who had both fever and cough during the peak influenza period for each year 2007 to 2009. In a completely circular manner the peak influenza period was defined as the four consecutive weeks with the highest Flutracking ILI rates. No analysis was performed of whether any symptom correlated with laboratory-proven influenza (Dalton 2011). A study of “influenza activity” in Hong Kong also achieved circularity by confounding together the laboratory proven influenza rate and the ILI rate: “The product of the laboratory influenza detection rate and the GP ILI consultation rate was used as the reference standard indicator of influenza virus activity, rather than the laboratory data alone which suffer from denominator dilution during periods of non-influenza epidemics and the GP ILI data alone which suffer from numerator dilution because not all ILI episodes are associated with influenza” (Lau 2012).  

5. Some studies argue that multiple viral activity databases which may have peaks at similar times measure the same phenomenon. A study in Singapore during the 2009 pandemic defined ILI by the WHO criteria, plus new onset respiratory symptoms and temperature > 38°C and multiplied the rate of ILI cases diagnosed by 23 sentinel GPs (n of patients not stated) by the “relative proportion of ILI seen by the average GP” and thereby estimated the ILI rate at 15% (Bayesian credible intervals 10%, 25%). A separate serological study of samples from 727 adult patients four weeks before, four weeks after the epidemic peak and four weeks after the epidemic subsided estimated the influenza rate at 17% (BCI 14%, 20%) and the two rates were presented as confirming each other. There was no relationship between the two samples, which were merely used to attempt estimates of the rate of ILI and influenza activity during the epidemic and no assessment was made of the utility of the ILI definition (Lee 2011). A study of “influenza activity” during 166 weeks in the US 2003-8 compared the CDC Outpatient ILI Surveillance Network (which uses the CDC ILI definition and a network of “health care providers”), Google Flu Trends (weekly percentage of persons seeking health care with ILI) and the CDC Influenza Virologic Surveillance System. The Pearson correlation coefficient between Google Flu trends and CDC Virus surveillance was 0.72 (95% CI 0.64 to 0.79) and with CDC ILI surveillance was 0.94 (95% CI 0.92 to 0.96) and between the two CDC databases 0.85 (0.81 to 0.89). There was no attempt to identify individuals across all three databases and no assessment of the utility of symptoms (Ortiz 2011).

6. Influenza rapid diagnostic tests have low sensitivity. There is an increasing tendency to use rapid influenza diagnostic tests for ILI cases. A review of 159 studies evaluating 26 rapid influenza diagnostic tests found the pooled sensitivity was 62.3% (95% CI 57.9% to 66.6%) and specificity 98% (97.5% to 98.7%), with lower sensitivity in adults 53.9% (47.9% to 59.8%). If these are used to assess the effectiveness of influenza vaccines further inaccuracy will be introduced (Chartrand 2012).

Appendix 2. Reasons not to use all-cause mortality as an outcome measure in assessing the effectiveness of influenza vaccines

All-cause mortality

There are three reasons not use all-cause mortality to assess the effectiveness of influenza vaccine.

1. Mortality attributable to influenza is a small proportion of all deaths. For those aged ≥ 65 in the US national multiple-cause-of-death databases 1968 to 2001 mortality attributable to pneumonia or influenza never exceeded 10% of all winter deaths (Simonsen 2006). All-cause deaths could be subject to considerable bias and fluctuations as an estimate of influenza mortality.

2. The number of nursing home residents with proven respiratory infections is low. A unique inclusive prospective study in France of 44,869 nursing home residents aged ≥ 65 found < 4.5% of the nursing home residents studied had an upper or lower respiratory tract infection, with 1.31% definite (95% CI 1.09 to 1.68) (using McGeer’s consensus definition, which is a physician diagnosis (McGeer 1991)) and 3.34% probable (2.88 to 3.87). Influenza vaccine had been received by 93.4% of the patients and pneumococcal vaccine by 13% (Chami 2011).

3. Many cases of "influenza" are not laboratory-proven and deaths are not recorded on death certificates. Three statistical approaches have attempted to use existing databases to predict mortality due to influenza.

a. The first assumes all differences in mortality comparing virus and non-virus seasons are due to influenza. A study in France using data from a sentinel network of GPs estimated only 3.35% (176,053) of all 5,295,480 deaths from 1998 to 2007 were due to ILI and 2.14% (113,240) due to cold spells. Mortality in the four winter months correlated with reported ILI (r = 0.75, P = 0.02) (Pin 2012). A study in the US and Japan had similar findings (Charu 2011). Mortality due to influenza cannot be estimated from these ILI data.

b. The second distributes “influenza related deaths” among co-morbidities. A study of weekly mortality data from the US National Health Statistics database 1997 to 2007 attributed an average of 11.92 (95% CI 10.1 to 13.6) deaths/100,000 to influenza, with 9.41 (8.3 to 10.5) to A/H3N2 years and 2.51 to influenza B years. These 11.92 deaths/100,000 ascribed to influenza were then further partitioned into: all circulatory causes 4.6 (3.79 to 5.39), all respiratory 3.58 (3.04 to 4.14), cancer 0.87 (0.68 to 1.05), diabetes 0.33 (0.26 to 0.39), renal disease 0.19 (0.14 to 0.24), CNS 0.42 (0.31 to 0.53) and Alzheimer’s 0.41 (0.3 to 0.52) and the authors concluded that 69% of the “influenza associated mortality” was attributable to circulatory and respiratory causes (Goldstein 2012). A study in the US and South Africa estimated excess deaths over baseline winter deaths as 16% for South Africa and 6% for the US. Within co-morbidity diagnoses the percentage of excess deaths over baseline winter deaths for all respiratory causes was estimated as 25% and 14%, for pneumonia and influenza as 29% and 20%, for cerebrovascular events as 16% and 4%, for diabetes as 13% and 5% and for ischaemic heart disease as 9% and 6% (Cohen 2010). A study in Canada assumed that recorded influenza-certified deaths substantially underrepresented influenza activity and estimated there were 3834 (1.9%) “influenza-attributable deaths” and allocated 877 to ischaemic heart disease, 563 to pneumonia, 529 to chronic obstructive pulmonary disease (COPD), 349 to other heart disease, 295 to cancer and 249 to stroke and then assessed whether their statistical model provided good predictions of these allocated deaths (Schanzer 2007).The precise number of deaths due to influenza cannot be known from these data and statistical methods.

c. The third computes a moving mortality average for the 13-month period centred on each month, assuming that these 13 month periods would be “unaffected by preceding or following epidemics.” For each disease class and month the 13-month moving average is then subtracted from the observed mortality. For unpublished data 1959 to 1999 from the public use data files of the US National Center for Health Statistics the authors created a time series for each class with a common metric by converting data into z scores with a mean of zero and standard deviation of 1. The peak months for pneumonia and influenza coincided with those for ischaemic heart disease 34 of 40 times, with cerebrovascular disease 33 of 40 times and with diabetes 30 of 40 times. However, midwinter peaks for pneumonia and influenza, ischaemic heart disease, cerebrovascular disease and diabetes varied in size and differed widely in mean values and seasonal variation. As expected, the tallest peaks in mortality curves occurred during the A(H3N2) 1968/9 pandemic and were lower in years where influenza A(H1N1) and B predominated and categorisation by influenza type correctly sorted winter seasons as having low or high mortality, without requiring additional information (Reichert 2004). The precise number of deaths due to influenza cannot be known from these data and statistical methods.

Appendix 3. Previous search

For our original search in 2006 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 2005) and Science Citation Index-Expanded (1974 to March 2006).

MEDLINE was searched using the following search terms in combination with stages I, II and III of the highly sensitive search strategy defined by The Cochrane Collaboration and detailed in Appendix 5b of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2005).

MEDLINE (OVID)

1 exp INFLUENZA/
2 influenza.mp.
3 or/1-2
4 exp VACCINES/
5 exp VACCINATION/
6 (immuniz$ or immunis$).mp.
7 vaccin$.mp.
8 or/4-7
9 3 and 8
10 exp Influenza Vaccine/
11 (influenz$ adj (vaccin$ or immun$)).mp.
12 or/10-11
13 9 or 12
14 exp Health Personnel/
15 (health personnel or healthcare personnel or health care personnel).mp.
16 (health worker$ or healthcare worker$ or health care worker$).mp.
17 (healthcare provider$ or health care provider$).mp.
18 (health practitioner$ or healthcare practitioner$ or health care practitioner$).mp.
19 health employee$.mp.
20 medical staff.mp.
21 (doctor$ or physician$).mp.
22 (allied health adj (staff or personnel)).mp.
23 paramedic$.mp.
24 nursing staff.mp.
25 nurse$.mp.
26 nursing auxiliar$.mp.
27 hospital personnel.mp.
28 hospital staff.mp.
29 hospital worker$.mp.
30 exp HOSPITALS/
31 exp Long-Term Care/
32 exp Residential Facilities/
33 nursing home$.mp.
34 (institution$ adj3 elderly).mp.
35 or/14-34
36 13 and 35

This strategy was adapted to search the other electronic databases. See below for the EMBASE search strategy. There were no language or publication restrictions. The search of CENTRAL included trial reports identified in the systematic search by hand of the journal Vaccine. To identify additional published and unpublished studies the Science Citation Index-Expanded was used to identify articles that cite the relevant studies. The relevant studies were also keyed into PubMed and the Related Articles feature used.

EMBASE (WebSPIRS)

#1 explode 'influenza-' / all subheadings in DEM,DER,DRM,DRR
#2 (influenza in ti) or (influenza in ab)
#3 #1 or #2
#4 explode 'vaccine-' / all subheadings in DEM,DER,DRM,DRR
#5 explode 'vaccination-' / all subheadings in DEM,DER,DRM,DRR
#6 (immuniz* in ti) or (immuniz* in ab)
#7 (immunis* in ti) or (immunis* in ab)
#8 (vaccin* in ti) or (vaccin* in ab)
#9 #4 or #5 or #6 or #7 or #8
#10 #3 and #9
#11 explode 'influenza-vaccine' / all subheadings in DEM,DER,DRM,DRR
#12 explode 'influenza-vaccination' / all subheadings in DEM,DER,DRM,DRR
#13 (influenz* adj (vaccin* or immun*)) in ti
#14 (influenz* adj (vaccin* or immun*)) in ab
#15 #10 or #11 or #12 or #13 or #14
#16 explode 'health-care-personnel' / all subheadings in DEM,DER,DRM,DRR
#17 (health personnel or healthcare personnel or health care personnel) in ti
#18 (health personnel or healthcare personnel or health care personnel) in ab
#19 (health worker* or healthcare worker* or health care worker*) in ti
#20 (healthcare provider* or health care provider*) in ti
#21 (healthcare provider* or health care provider*) in ab
#22 (health practitioner* or healthcare practitioner* or health care practitioner*) in ti
#23 (health practitioner* or healthcare practitioner* or health care practitioner*) in ab
#24 (health employee* in ti) or (health employee* in ab)
#25 explode 'hospital-personnel' / all subheadings in DEM,DER,DRM,DRR
#26 explode 'hospital-physician' / all subheadings in DEM,DER,DRM,DRR
#27 explode 'medical-personnel' / all subheadings in DEM,DER,DRM,DRR
#28 (medical staff in ti) or (medical staff in ab)
#29 explode 'physician-' / all subheadings in DEM,DER,DRM,DRR
#30 (doctor* or physician*) in ti
#31 (doctor* or physician*) in ab
#32 (allied health adj (staff or personnel)) in ti
#33 explode 'paramedical-personnel' / all subheadings in DEM,DER,DRM,DRR
#34 ( paramedic* in ti) or ( paramedic* in ab)
#35 explode 'nursing-staff' / all subheadings in DEM,DER,DRM,DRR
#36 ( nursing staff in ti) or ( nursing staff in ab)
#37 ( nurse* in ti) or ( nurse* in ab)
#38 ( nursing auxiliar* in ti) or ( nursing auxiliar* in ab)
#39 (hospital staff in ti) or (hospital staff in ab)
#40 (hospital worker* in ti) or (hospital worker* in ab)
#41 explode 'hospital-' / all subheadings in DEM,DER,DRM,DRR
#42 explode 'long-term-care' / all subheadings in DEM,DER,DRM,DRR
#43 explode 'residential-care' / all subheadings in DEM,DER,DRM,DRR
#44 explode 'residential-home' / all subheadings in DEM,DER,DRM,DRR
#45 (nursing home* in ti) or (nursing home* in ab)
#46 (institution* adj elderly) in ti
#47 (institution* adj elderly) in ab
#48 #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47
#49 #15 and #48

Bibliographies of all relevant articles were obtained and any published review and proceedings from relevant conferences were assessed for additional studies. We explored Internet sources in December 2005: NHS National Research Register (http://www.update-software.com/national/); the metaRegister of Clinical Trials (http://www.controlled-trials.com/) and the digital dissertations website (http://wwwlib.umi.com/dissertations). The Vaccine Adverse Event Reporting System website was searched (http://www.vaers.org). We contacted first or corresponding authors of relevant studies to identify further published or unpublished trials.

For the update search in September 2009 we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register and the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (January 1966 to Week 3, September 2009); EMBASE (1974 to September 2009); Biological Abstracts (1969 to December 2005) and Science Citation Index-Expanded (1974 to September 2009), which included Science Citation Index-Expanded, Biosis Previews and Current Contents. There were no language restrictions.

Appendix 4. EMBASE search strategy

Embase.com

#23 #11 AND #22
#22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#21 (('long stay' OR 'long term') NEAR/2 (ward* OR facilit* OR hospital*)):ab,ti
#20 'nursing home':ab,ti OR 'nursing homes':ab,ti OR 'aged care':ab,ti OR hospice*:ab,ti OR (institution* NEAR/3 elderly):ab,ti OR 'old peoples homes':ab,ti OR 'old peoples home':ab,ti
#19 'health care facility'/de OR 'hospice'/de OR 'nursing home'/de OR 'residential home'/de OR 'geriatric hospital'/de OR 'hospital'/de OR 'public hospital'/de OR 'private hospital'/de
#18 (nursing NEAR/2 (staff OR personnel OR auxiliar* OR assistan*)):ab,ti
#17 paramedic*:ab,ti OR nurse*:ab,ti
#16 ('allied health' NEAR/2 (personnel OR staff OR employee* OR worker* OR professional*)):ab,ti
#15 doctor*:ab,ti OR physician*:ab,ti OR clinician*:ab,ti
#14 ((medical OR hospital) NEAR/2 (staff OR employee* OR personnel OR worker*)):ab,ti
#13 ((health OR 'health care' OR healthcare) NEAR/2 (personnel OR worker* OR provider* OR employee* OR staff OR professional*)):ab,ti
#12 'health care personnel'/exp
#11 #1 OR #10
#10 #5 AND #9
#9 #6 OR #7 OR #8
#8 immuniz*:ab,ti OR immunis*:ab,ti
#7 'immunization'/exp
#6 'vaccine'/exp OR 'vaccination'/de
#5 #2 OR #3 OR #4
#4 'influenza virus a'/exp OR 'influenza virus b'/de
#3 influenza*:ab,ti OR flu:ab,ti
#2 'influenza'/exp
#1 'influenza vaccine'/de

Appendix 5. Web of Science search strategy

# 6 103

#4 AND #3

Refined by: Publication Years=( 2011 OR 2010 OR 2009 OR 2012 )

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

# 5 301

#4 AND #3

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

# 4 1,300,160

Topic=(random* or placebo* or crossover* or "cross over" or allocat* or ((singl* or doubl*) NEAR/1 blind*)) OR Title=(trial)

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

# 3 981

#2 AND #1

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

# 2 88,201

Topic=(((health or "health care" or healthcare or hospital or medical) NEAR/2 (personnel or worker* or employee* or staff or professional*)) or doctor* or physician* or clinician* or nurs* or paramedic* or "allied health") AND Topic=(hospital* or hospice* or "residential facilities" or "residential facility" or "nursing homes" or "nursing home" or "aged care" or "old peoples home" or "old peoples homes" or (institution* NEAR/3 elderly) or (("long term" or "long stay") NEAR/3 (ward* or facilit* or hospital*)))

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

# 1 16,674

Topic=((influenza* or flu) NEAR/4 (vaccin* or immunis* or immuniz*))

Databases=SCI-EXPANDED, CPCI-S Timespan=All Years

Lemmatization=On  

Appendix 6. SIGN search strategy for observational studies

1 epidemiologic studies/
2 exp case-control studies/
3 exp Cohort Studies/
4 case control.tw.
5 (cohort adj (study or studies)).tw.
6 cohort analy*.tw.
7 (follow up adj (study or studies)).tw.
8 (observational adj (study or studies)).tw.
9 longitudinal.tw.
10 retrospective.tw.
11 cross sectional.tw.
12 Cross-Sectional Studies/
13 or/1-12

Appendix 7. Assessment of Oshitani 2000 using the Newcastle-Ottawa Scale for non-RCTs (Wells 2005)New Appendix

Selection

1. Representativeness of the exposed cohort:
a. truly representative of the average Long Term Care Facilities in Niigata Prefecture and City (mandatory surveys of influenza vaccination status and influenza-like illness occurrence every 2 weeks January to March 1999) in the community
b. somewhat representative of the average ___________ in the community
c. selected group of users (e.g. nurses, volunteers)
d. no description of the derivation of the cohort

2. Selection of the non-exposed cohort:
a. drawn from the same community as the exposed cohort
b. drawn from a different source
c. no description of the derivation of the non-exposed cohort

3. Ascertainment of exposure to influenza vaccine:
a. secure record (e.g. surgical records)
b. structured interview. "Mandatory survey." "Influenza vaccine had been given to 3933 residents (30.8%). No resident had received vaccine in 75 facilities (50.3%). Vaccines had also been given to 1532 of 7459 staff and10 or more staff had been vaccinated in 47 facilities (31.5%)." No description of survey or how administered or how completeness ascertained.
c. written self report
d. no description

4. Demonstration that outcome of interest was not present at start of study:
a. yes "An influenza outbreak was defined when the number of ILI per week exceeded 10% of the residents"
b. no

Comparability

1. Comparability of cohorts on the basis of the design or analysis:
a. study controls for differences in demographic characteristics and co-morbidities of residents who were vaccinated and characteristics of homes where residents received vaccination (select the most important factor) No
b. study controls for any additional factor: geriatric health services facilities compared to special nursing homes for those with more severe conditions (this criteria could be modified to indicate specific control for a second important factor) No

Outcome

1. Assessment of outcome:
a. independent blind assessment
b. record linkage
c. self report "Mandatory survey every 2 weeks January to March 1999"
d. no description

2. Was follow-up long enough for outcomes to occur (select an adequate follow-up period for outcome of interest):
a. yes - January to March 1999
b. no

3. Adequacy of follow-up of cohorts:
a. complete follow-up - all subjects accounted for
b. subjects lost to follow-up unlikely to introduce bias - small number lost (> ___ % (select an adequate %) to follow-up, or description of those lost))
c. follow-up rate < ___% (select an adequate %) and no description of those lost
d. no statement. No statement of admissions, deaths or separations from homes during study period. Total number of residents in Table 2 in homes where < 10 staff vaccinated is listed as 8699 but subcategories add to 8669 andin homes where >= 10 staff vaccinated listed as 4085 but subcategories add to 4073

Feedback

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've 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.

Reply

We thank Thomas Kristiansen for his comment. The article was in fact published in the Journal of Infectious Diseases (volume 175), issue 1 in 1997. It is available for purchase or download at: http://www.jstor.org/pss/30129986.

Contributors

Thomas Birk Kristiansen
Feedback comment added 21 June 2008

Influenza vaccination for healthcare workers who work with the elderly, 1 December 2009

Summary

In the table and list of included studies, you have reported Hayward 2006 (BMJ Des 2006) but this study is not included in the analyses or mentioned in the text. The outcomes of this study do not seem to be adequately reported in the table.

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.

Reply

We thank Signe Flottorp for his comment, which we received as we were updating the review. His comment has now been addressed.

Contributors

Signe Flottorp

What's new

DateEventDescription
31 March 2013New citation required and conclusions have changedBased on our literature review, we now determine that two outcome measures, (influenza-like illness (ILI) (Appendix 1) and all-cause mortality (Appendix 2)), reported in the first and second publications of this review, are inappropriate measures of influenza vaccine effectiveness. They are not registered indications for the vaccine. Therefore, the outcome data from Hayward 2006 (main outcome measure all-cause mortality and secondary outcome measure ILI) and Oshitani 2000 (outcome measure ILI) are no longer presented.
31 March 2013New search has been performedSearches conducted. No new trials were included in this 2013 review update.

History

Protocol first published: Issue 2, 2005
Review first published: Issue 3, 2006

DateEventDescription
10 December 2009Feedback has been incorporatedFeedback comment and reply added.
21 June 2008Feedback has been incorporatedFeedback comment added.
13 May 2008AmendedConverted to new review format.
23 May 2006New search has been performedReview first published, Issue 3, 2006.

Contributions of authors

Responsible for the design of the review: Roger Thomas (RET), Tom Jefferson (TOJ).
Responsible for data extraction: all authors.
Responsible for the assessment of study quality and outcomes: RET and TJL (Toby Lasserson).
Responsible for the first draft: RET.
Responsible for the final draft: RET, TOJ, TJL

Declarations of interest

Dr. Jefferson receives royalties from his books published by Blackwell and Il Pensiero Scientifico Editore, Rome. Dr Jefferson is co-recipient of a UK National Institute for Health Research grant to carry out a Cochrane review of neuraminidase inhibitors (http://www.hta.ac.uk/2352). In 1997-99 Dr Jefferson acted as consultant for Roche, in 2001-2 for GSK and in 2003 for Sanofi. In 2011-2012,  Dr Jefferson acted as an expert witness in a litigation case related to an antiviral (oseltamivir phosphate; Tamiflu (Roche)). Dr Jefferson is on a legal retainer for expert advice on litigation for influenza vaccines in healthcare workers. No declarations of interest for Dr. Roger Thomas or Toby Lasserson.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Institute for Health Research (NIHR), UK.

    Competitive grant awarded through The Cochrane Collaboration

  • National Health and Medical Research Council (NHMRC), Australia.

    Competitive grant to Chris Del Mar and Tom Jefferson, 2009

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Carman 2000

Methods

Purpose: to assess the effects of staff vaccination against influenza on resident mortality in long-term care hospitals

Design: cluster-randomised study (C-RCT) conducted in Scotland during the 1996 to 1997 influenza season. The study identified 10 long-term care geriatric hospitals 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 HCWs to be offered influenza vaccination or not

Anonymous questionnaires were sent to ward nurses on 31 March 1997 to ask if they had received influenza vaccination and these data were used to estimate vaccine acceptance for all HCWs in hospitals where influenza vaccine had not been offered to HCWs. 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 GPs were used to define the start of the influenza season. Combined nasal and throat swabs were taken from patients every 2 weeks from 14 December 1996 to 14 February 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 analyzed by RT-PCR analysis

Results were summarised for the 2 groups of LTCIs. Hospitals were not well-matched for patient vaccination rates and Barthel scores (Wikipedia 2009) 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)

Statistics: the power calculation was based on the previous study by Potter 1997 and the authors computed that with 1600 patients in 20 hospitals they would have ≥ 80% power to detect a decrease in mortality from 15% to 10% with alpha = 0.05 (2-tailed), allowing for the clustered design. The power calculation for virological sampling showed that 500 patients would be required to give 80% power at 5% significance (2-tailed) to detect a decrease in influenza infection from 25% to 15%

Mortality rates were compared in the 2 groups with the Mann-Whitney test. "Incomplete data for patient-level covariates meant that a full multilevel approach to the analysis was not possible without making strong, implausible and untestable assumptions about the mechanisms that led to the incomplete data. Instead, we calculated summary statistics to describe the mix of patients in each hospital and these values were included in a multiple linear-regression analysis. The response variable in these analyses was the empirical logit of each hospital's mortality rate that is, the natural logarithm of the odds on death."

Participants

Country: Scotland

Setting: 20 long-term care hospitals in Glasgow

Eligible participants: 749 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

Age: 82

Gender: 70% F

Interventions

Intervention: influenza vaccination. The type, dosage and route are not described. A good match in the study year between the prevailing strain and the vaccine strains was reported

Control: no influenza vaccination

Outcomes
  1. RT-PCR and tissue culture for influenza A or B. A random sample of 50% of patients in each hospital was selected for virological monitoring of influenza infections by nose and throat swabs every 2 weeks, which were sent for RT-PCR analysis and tissue culture. "At the times when study nurses took routine samples, they took additional opportunistic nose and throat swabs from non-randomised patients who the ward nurses thought had an influenza-like illness. The ward staff were asked to take routine nasal swabs within 12 hours of death for any patient who died."

  2. Mortality (all causes)

(N.B. clinical outcomes were not reported but were used to investigate the viral circulation in the facility)

Notes

The situation that 10 long-term care hospitals 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 HCWs within each of these clusters
Analysis was not according to intention-to-treat

Design effect: 2.6; source: intra-cluster variance of 2.3% reported in Hayward 2006a

Despite no difference in isolation of influenza viruses between clusters, the authors conclude that vaccines are protective. In addition, they fail to comment on the implausibility of the vaccines' effect on aspecific outcomes (ILI) and lack of effect on influenza

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Hospitals were randomly allocated ... by random-numbers table."
Allocation concealment (selection bias)Unclear riskNot stated
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskIn the 10 hospitals where HCWs were offered vaccination 749 patients were included and "a random sample of 375 patients was offered virological screening by nose/throat swab"; 258 accepted. In the 10 hospitals where HCWs were not offered vaccination 688 patients were included and a random sample of 344 were offered virological screening by nose/throat swab; 269 accepted. Note comments by authors in the Description section above on incomplete data. Polymerase chain reaction (PCR) samples were obtained from only 17% of deaths. Four samples from each patient surveyed were planned from protocol: 1798 samples were obtained from 719 patients (2.5 samples/patient)
Selective reporting (reporting bias)Low riskNo selective reporting
Other biasHigh risk
  1. Selection bias: the total number of long-term care hospitals in West and Central Scotland is not stated. In the long-term care hospitals in which HCWs were offered vaccination, residents had higher Barthel scores

  2. Performance bias: only 51% of HCWs in the arm received vaccine in the long-term care hospitals where vaccine was offered and 4.8% where it was not; 48% of patients received vaccine in the arm where HCWs were offered vaccination and 33% in the arm where HCWs were not

  3. Statistical bias: the analysis was not corrected for clustering, unlike the Potter 1997 pilot; in the long-term care hospitals where HCWs were offered vaccination, the patients had significantly higher Barthel scores and were more likely to receive influenza vaccine (no significance level stated) and due to missing data these differences could not be adjusted for other than by estimation. Statistical power may also have been a problem as the detection rate of 6.7% was lower than the estimated rate of 25% used in the power calculation

Hayward 2006

Methods

Purpose: to increase staff vaccination rates in care homes by adoption of a policy to encourage staff to be vaccinated against influenza and providing vaccination clinics

Design: C-RCT; 48 nursing homes were placed in matched pairs (by size of home, % of high dependency and mortality of residents) within 3 regions (northern, central and southern England), then the 25 homes which most closely matched were selected and randomised by a researcher, blinded to the home’s identity and characteristics, using a table of random numbers. Data from the Royal College of General Practitioners sentinel surveillance scheme were used to divide the study into periods of influenza activity and no influenza activity

Duration of study: 3 November 2003 to 28 March 2004 and 1 November 2004 to 27 March 2005

Interval between intervention and when outcome was measured: 3 November 2003 to 28 March 2004 and 1 November 2004 to 27 March 2005

Power computation: to detect reduction in all-cause mortality of residents from 15% to 10% (intra-cluster variance = 2.3%) with 90% power and alpha = 0.05% level required 20 pairs of homes each with an average of 20 residents (based on findings from pilot study)

Statistics: outcomes were analyzed using aggregate data for each cluster and "to take account of the matched clustered design we used a random-effects meta-analysis. This treated the results from each pair of homes as a separate study and provided a pooled estimate of effect weighted for the size of homes and the size of the effects and their standard errors." "When significant protection of residents was observed we calculated the number of staff vaccinations needed to prevent one event in residents (number needed to treat) as number of vaccinations given in all intervention homes divided by the average number of residents in all intervention homes multiplied by the weighted rate difference."

ParticipantsCountry: UK
Setting: private chain of nursing homes, whose policy was not to offer influenza vaccination to staff
Eligible participants: (health status): 1 intervention and 1 control home were unable to provide data so they and their matched home were excluded, leaving 44 homes for analysis; eligible staff were all staff in intervention homes (full-time: n = 844 in both 2003 to 2004 and in 2004 to 2005) and (part-time: n = 766 in 2003 to 2004 and n = 882 in 2004 to 2005)
Age: Avg 83
Gender: 71% F
InterventionsIntervention 1: Adoption of policy in intervention homes of vaccinating staff against influenza, including a lead nurse in each home was trained to promote vaccination of staff; distribute leaflets and posters and liaise to provide 3 vaccination clinics for staff in each home. Staff were sent a letter explaining the study and the potential benefits of influenza vaccination
Control: staff in control homes received a letter describing the study and the Department of Health recommendation that those with chronic illnesses should receive influenza vaccination
No attempt to influence vaccination of residents in any home
OutcomesPrimary outcome of the study: to assess effect of vaccinating staff on all-cause mortality of residents
Secondary outcomes: ILI (defined as fever 37.8°C measured orally, or an acute deterioration in physical or mental ability, plus either new onset or one or more respiratory symptoms or an acute worsening of a chronic condition involving respiratory symptoms), mortality with ILI, admission to hospital from any cause, admission to hospital with ILI and consultations with a GP for ILI
Other outcomes measured: % of staff vaccinated
Time points from the study that are considered in the review or measured or reported in the study: 3 November 2003 to 28 March 2004 and 1 November 2004 to 27 March 2005
% of staff vaccinated: by 28 March 2004 for first year of study and by 27 March 2005 for second year of study: full-time staff: intervention group 407/844 vaccinated; control group 51/859
Part-time staff: intervention group 163/766 vaccinated; control group 33/815
NotesFunding: UK Department of Health
Design effect: 2.3; source: calculation based on reported intra-cluster variance (2.3%) in the published paper
Vaccine content was not reported. No conclusions on matching can be drawn
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"A researcher blinded to the home’s identity and characteristics carried out randomisation within those pairs using random number tables."
Allocation concealment (selection bias)Low risk"A researcher blinded to the home’s identity and characteristics carried out randomisation."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo statement
Incomplete outcome data (attrition bias)
All outcomes
High risk"No outcome data were available for the excluded homes so an intention to treat analysis was not possible."
Selective reporting (reporting bias)Unclear riskAlthough the study does not contribute data for relevant outcomes we are unable to ascertain whether influenza specific outcome data were collected and analyzed
Other biasLow riskNo other issues were identified

Lemaitre 2009

Methods

Purpose: to assess the effect of staff and resident influenza vaccination on resident all-cause mortality

Design: C-RCT. A written invitation was sent to the 376 nursing homes with 50 to 200 elderly people (out of a total 1105 nursing homes) in the Paris area and 88 responded. Of these 40 with staff influenza coverage < 40% during the 2005 to 2006 winter season were selected. Each institution was pair-matched on size, staff vaccination coverage 2005 to 2006 and Group Iso Resources (GIR) weighted average disability score (which ranges from 1 = severe disability to 6 = total autonomy). Randomisation was centrally based using a random-number generator

Statistics: it was assumed that the influenza epidemic would last 2 months, mortality would be 8% in the control arm and resident mortality would be reduced 40% after staff vaccination to 4.8% in the intervention arm. 20 pairs of nursing homes with 2000 residents in each group were required to obtain 80% power with 2-tailed hypothesis testing. Analysis was by intention-to-treat. "Odds ratios were calculated using alternating logistic regression, with one-nested log odds ratios to model the association between the responses of the same pair and the same nursing home within the pair." "In secondary analyses, multivariate estimates were adjusted for the residents' age, vaccination status, GIR disability score and Charlson comorbidity index."

Participants

Country: France

Setting: 40 nursing homes near Paris

Eligible participants: 3483 patients in the 40 nursing homes

In the intervention arm there were 1592 residents at the beginning and 130 entered the homes during the study period (total = 1722); 989 staff were present at recruitment and 678 (68.6%) were vaccinated. In the control arm there were 1558 residents at the beginning and 120 entered the homes during the study period (total = 1678); there were 1015 staff at recruitment and 323 (31.8%) were vaccinated

1452 (84.3%) of patients in the intervention and 1385 (82.5%) in the control group were vaccinated during the 2005 to 2006 winter season

Age: 86

Gender: 77.% F

Interventions

Intervention:

  1. Promotional campaign with posters, leaflets and an information meeting with the study team to sensitise staff to the benefits of influenza vaccination for oneself and residents

  2. Face-to-face interviews with each member of staff present in nursing homes between 6 November and 15 December 2006

  3. The study team met all administrative staff, technicians and caregivers to invite them to participate and those who volunteered were vaccinated at the end of the interview. The vaccine was inactivated Influvac (Solvay Pharma Laboratories), with 15 µG of each of A/Wisconsin/67/2005-like (H3N2), A/New Caledonia/20/99 (H1NH1) and B/Malaysia/2506/2004

Control: routine information on influenza vaccination

Outcomes

Primary: all-cause mortality

Secondary:

  1. Influenza, measured when clusters of ILI occurred in residents, using the Quick View Influenza Test

  2. ILI ("defined as a fever of ≥ 37.8°C and onset of respiratory symptoms or worsening of chronic respiratory conditions"

  3. Proportion of staff who reported ≥ 1 day of sick leave

Notes

Design effect: 1.9; source: reported in published paper and confirmed by Magali Lemaitre

Choice of main outcome is inappropriate

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Randomisation was centrally based using a random-number generator"
Allocation concealment (selection bias)Unclear riskNot stated
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Low risk

During primary study period. Intervention group: 1592 residents at beginning + 130 entered and 1722 analyzed; Control group: 1558 residents at the beginning, 120 entered, 1678 analyzed (no statement of deaths or separations)

Intervention group 989 staff (678 vaccinated); Control group 1015 staff (estimated vaccination rate 31.8%)

Selective reporting (reporting bias)Low riskNo selective reporting
Other biasHigh riskPerformance bias (delivery of influenza vaccine to intervention arm)

Oshitani 2000

MethodsPurpose: to assess the effect of staff and resident influenza vaccination rates on resident influenza-like illness (ILI)
Design: prospective cohort study assessing the effectiveness of influenza vaccination levels in patients of long-term nursing care facilities (LTCIs) by vaccination coverage rates of HCWs (less than 10 or more than 10 vaccinated HCWs per facility), in Niigata, Japan. Niigata Prefecture and Niigata City conducted mandatory surveys of influenza vaccine status and occurrence of ILI every 2 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 LTCIs 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
An influenza outbreak was defined as 10% of more of the residents in a home reporting ILI symptoms during a week
Two types of LTCIs, 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
Statistics: X2 and Fisher’s exact test for univariate analysis. X2 for linear trend and Mantel-Haenszel ORs for different categories of resident vaccination rates. Logistic regression for multivariate analysis of outbreak status
ParticipantsCountry: Japan
Setting: 149 LTCIs in Niigata Prefecture and Niigata City
Eligible participants: the text reports 12,784 residents in 149 facilities were included in the study with 3933 (30.8%) vaccinated and 7459 staff with 1532 (20.5%) vaccinated However, table 2 shows 8669 residents living in homes where fewer than 10 staff were vaccinated and 4073 living in homes with 10 staff vaccinated, for a total of 12,742. The totals for residents living in homes with fewer than 10 staff vaccinated is given as 8699 but the subcategories add to 8669 and for the homes where 10 staff were vaccinated the total is given as 4085 but the subcategories add to 4073
Age: not stated
Gender: not stated
InterventionsIntervention: 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 pneumococcal vaccination is made
Control: no control group
OutcomesILI (no case definition). During the period of surveying the number of ILI cases per week exceeded 10% of the residents in 34 (22.8%) of facilities
Notes

Choice of outcome is inappropriate (ILI is an a non-specific outcome)

Assessment of the Oshitani study was undertaken with the Newcastle-Ottawa scale (see Appendix 7)

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk-
Allocation concealment (selection bias)Unclear risk-
Blinding (performance bias and detection bias)
All outcomes
Unclear risk-
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-
Selective reporting (reporting bias)Unclear risk-
Other biasUnclear risk-

Potter 1997

  1. a

    Avg: average
    C-RCT: cluster-randomised controlled trial
    F: female
    HCWs: healthcare workers
    ILI: influenza-like illness
    LRTI: lower respiratory tract infection
    LTC: long-term care
    PCR: polymerase chain reaction
    RCT: randomised controlled trial
    RT-PCR: reverse-transcriptase polymerase chain reaction
    S0P0: staff and patients not vaccinated
    S0PV: staff not vaccinated, patients vaccinated
    SVPV: staff and patients vaccinated
    SVP0: staff vaccinated and patients not vaccinated
    WBC: white blood cell

Methods

Purpose: to assess the effect of staff and patient vaccination against influenza on resident

  1. Serologically proven influenza

  2. ILI

  3. Lower respiratory tract infection

  4. Deaths (from all causes)

  5. Deaths (from pneumonia)

Design: 6 geriatric long-stay hospitals in Glasgow in 1994 had an "opt-out" policy in which patients were routinely given influenza vaccine unless they refused it or had a major contraindication and 6 had an "opt-in" policy in which patients were given vaccine only if they or their relatives requested it following advertisement on the ward that it was available

Hospitals were stratified by policy on vaccination then randomised for their HCWs to be "routinely offered either influenza vaccination or no vaccination." Study conducted in Scotland, during the 1994 to 1995 influenza season, in the community. Follow-up period was 1 October 1994 to 31 March 1995. 12 hospitals were randomly allocated to offer vaccination of HCWs 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 (S0P0)
- staff not vaccinated, patients vaccinated (S0PV)
- staff and patients vaccinated (SVPV)
- staff vaccinated and patients not vaccinated (SVP0)

Statistical analysis: "Baseline characteristics, morbidity and mortality in the 4 groups of hospitals were compared using the X2 test, unpaired Student's test and Wilcoxon rank sum test as appropriate. Odds ratios and 95% CIs were calculated for the effects of staff and patient vaccination. Survival analysis was by Kaplan-Meier product limit estimates, using the Tarone Ware test for statistical significance. Cluster analysis, examining mortality rates and other outcomes by hospital site, was also done."

Participants

Country: Scotland

Setting: 12 geriatric medical long-term care hospitals in Glasgow

Eligible participants: 1059 hospital residents. All 1078 HCWs (day and night nurses and nursing auxiliaries, ward cleaners, doctors, therapists and porters) in SVPV and SVP0 hospitals were offered vaccination but "voluntary workers, patients' friends and relatives and other casual or occasional ward visitors were not offered vaccine." Observed units were hospitals and not patients

654 (61%) of the 1078 agreed to participate; vaccination was contraindicated in 34 (3%) and 47 (4%) were on long-term sick leave and unavailable

The physical dependency level of patients was measured on the 20-point Barthel scale. The hospitals where patients were routinely offered vaccination (S0PV and SVPV) had lower Bartel scores (P = 0.003) than those not offered vaccination but there were no differences between hospitals where HCWs were vaccinated and those where they were not

Age: 77

Gender: 71% F

InterventionsVaccination of patients and HCWs began October 1994 ("4 weeks before the earliest likely start date of the annual influenza outbreak"). Parenteral influenza vaccine. Vaccine strains probably matched the circulating strain
Outcomes
  1. Serologically proven influenza (paired sera in 225 consenting patients in the "patients not vaccinated" arms)

  2. ILI (defined as a temperature of ≥ 37°C, "plus one of the following symptoms: new-onset cough, coryza, sore throat, malaise, headache, or muscle aches" - reported singly or within the ILI outcome) and was monitored from the end of October 1994 to the end of March 1995

  3. LRTI ("was identified by the presence of (1) pulmonary crackles, wheeze or tachypnoea plus temp ≥ 37 °C or WBC > 10 x 109/L or (2) a positive sputum culture" and was monitored from the end of October 1994 to the end of March 1995

  4. Deaths (from all causes)

  5. Deaths (from pneumonia)

All deaths and discharges and admissions to the wards were recorded

Ward staff notified the research nurse of any patient who developed clinical symptoms of upper respiratory tract viral illness, influenza or lower respiratory tract infection and the research nurse visited the patient within 24 hours to record symptoms, clinical signs and investigations on standardised forms. "Chest radiographs were not included as part of the routine assessment of suspected lower respiratory tract infection, as for many of the peripheral hospitals, it would have required an ambulance journey for the patient." "Patients with suspected viral illness who gave verbal consent had a nasopharyngeal aspirate (NPA) sample obtained within 48 hours of notification of symptoms. IFA for influenza A and B, respiratory syncytial virus (RSV), Chlamydia psittaci and adenovirus antigens" were obtained

Antibody levels to Mycoplasma pneumoniae (M. pneumoniae) were ascertained by complement fixation in consenting patients who had not received influenza vaccination

Notes

Staff vaccination was incomplete and variable; results were presented by hospital group and not by vaccination status of patients. The authors concluded that vaccination of HCWs was associated with lower mortality and ILI. These benefits were not evident vaccinating patients alone

Design effect: 3.0; source: intra-cluster variance of 2.3% reported in Hayward 2006

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

"Hospital sites were stratified by unit policy for vaccination, then randomised for their HCWs to be routinely offered either influenza vaccination and their patients unvaccinated (S0P0), staff vaccinated and patients unvaccinated (SVP0), staff unvaccinated and patients vaccinated (S0PV) and both staff and patients vaccinated (SVPV)"

(N.B. the phrase "either influenza vaccination and their patients unvaccinated (S0P0)" is an error and should read: "neither staff nor patients vaccinated (S0P0)")

Allocation concealment (selection bias)Unclear riskNot stated
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskOnly 654 (61%) of the 1078 HCWs agreed to participate and receive influenza vaccination and 478 (88.8%) of the 538 patients in the "routine vaccination of patients" arms. Serologically proven influenza was ascertained in paired sera in only 225 consenting patients in the "patients not vaccinated" arms. The numbers of influenza or ILI infections in HCWs were not reported
Selective reporting (reporting bias)Low riskNo selective reporting
Other biasHigh risk
  1. Selection bias: the total number of long-term care hospitals in West and Central Scotland is not stated. There were inconsistencies in outcome gradients (see Table 1). In the population under observation, Potter 1997 reported 216 cases of suspected viral illness, 64 cases of ILI, 55 cases of pneumonia, 72 deaths from pneumonia and 148 deaths from all causes; in the sub-population of both vaccinated staff and patients, Potter 1997 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 real effect of vaccination

  2. Performance bias: 67% of staff in active arm 1 and 43% in active arm 2 were vaccinated

  3. There is no description of the vaccines administered, vaccine matching or background influenza epidemiology

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    HCW: healthcare worker
    RCT: randomised controlled trial

Bellei 2007Surveillance study of influenza and rhinovirus infections among HCWs; no vaccination data; no data for elderly people
Bertin 2007Intranet assessment of HCW vaccination status; no vaccination or outcome data for elderly people
Carusone 2007Study of pneumonia and lower respiratory infections in nursing home residents as predictors of hospitalisation and mortality; based on previous RCT; influenza vaccination status of patients; no HCW vaccination data
Chicaíza-Becerra 2008Economic evaluation of influenza vaccination of HCWs; no vaccination or outcome data for elderly people
Chittaro 2009Influenza vaccination campaign for HCWs; no data on elderly people
del Villar-Belzunce 2007Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Doratotaj 2008Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Hood 2009Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Isaacs 1997Data were not presented by HCW vaccine coverage; only 21% of staff were vaccinated; amantadine was a confounder as it was given to patients and not staff; a flow sheet of admissions and discharges was not presented
Isahak 2007Programme to increase influenza vaccination among elderly people in long-term care homes; no vaccination data for HCWs
Kheok 2008Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Kimura 2007Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Landi 2006Prospective observational study of influenza vaccination in elderly people; no HCW data
Lee 2008Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Looijmans-van den AkkerSurvey of effect of national policy on influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Mangtani 2004Historical cohort study of individuals older than 64 years in the UK General Practice Research Database 1989 to 1999 in England and Wales. No intervention for HCWs
Munford 2008Campaign to increase influenza vaccination among elderly people and HCWs; no outcome data for elderly people
Sato 2005Study of antibody levels in elderly people and HCWs in response to influenza vaccination
Shugarman 2006Retrospective cross-sectional study of 344 nursing homes (310 replied) from one chain in the US, with reports of staff and resident vaccination rates and whether the home had an ILI cluster (≥ 3 residents with ILI within 72 hours)
Yang 2007Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people
Yassi 1993Data were not presented by HCW vaccine coverage. Vaccine and amantadine were used to control outbreak: amantadine acts as confounder
Zimmerman 2009Programme to increase influenza vaccination among HCWs; no vaccination or outcome data for elderly people

Ancillary