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Strategies to reduce non-ventilator-associated hospital-acquired pneumonia: A systematic review

Open AccessPublished:July 04, 2019DOI:https://doi.org/10.1016/j.idh.2019.06.002

      Highlights

      • There is considerable heterogeneity in the study design, interventions, methods and definitions used in NV-HAP studies.
      • Improving oral care, increased mobility or movement and dysphagia management appear to be key strategies in reducing NV-HAP.
      • Further research in a hospital setting, using robust designs are needed.

      Abstract

      Background

      Point prevalence studies identify that pneumonia is the most common healthcare associated infection. However, non-ventilator associated healthcare associated pneumonia (NV-HAP) is both underreported and understudied. Most research conducted to date, focuses on ventilator associated pneumonia. We conducted a systematic review, to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used.

      Methods

      We performed a systematic search to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities. The electronic database Medline was searched, for peer-reviewed articles published between 1st January 1998 and 31st August 2018. An assessment of the study quality and risk of bias of included articles was conducted using the Newcastle–Ottawa Scale.

      Results

      The literature search yielded 1551 articles, with 15 articles meeting the inclusion criteria. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9). Three studies evaluated a form of physical activity, such as passive movements, two studies used dysphagia screening and management; and another study evaluated prophylactic antibiotics. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials.

      Conclusion

      There was considerable heterogeneity in the included studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management.

      Keywords

      Introduction

      In recent years, there have been numerous initiatives to reduce certain healthcare-associated infections (HAIs), such as bloodstream infections [
      • Duerden B.
      • Fry C.
      • Johnson A.P.
      • Wilcox M.H.
      The control of methicillin-resistant Staphylococcus aureus blood stream infections in England.
      ], urinary tract infections [
      • Saint S.
      • Greene M.T.
      • Krein S.L.
      • Rogers M.A.
      • Ratz D.
      • Fowler K.E.
      • et al.
      A program to prevent catheter-associated urinary tract infection in acute care.
      ] and surgical site infections [
      National Health Safety Network
      Surgical site infection (SSI) documentation review checklist.
      ]. In some countries, there have also been government targets, incentives and penalties for specific HAIs, including central line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site infections (colon and hysterectomy), methicillin-resistant Staphylococcus aureus bacteremia and Clostridium (Clostridioides) difficile infections [
      • Centers for Medicare & Medicaid Services
      Hospital-acquired condition reduction program fiscal year 2019 fact sheet.
      ]. However, despite hospital-acquired pneumonia (HAP) reported as one of the most common HAIs [
      • Magill S.S.
      • O'Leary E.
      • Janelle S.J.
      • Thompson D.L.
      • Dumyati G.
      • Nadle J.
      • et al.
      Changes in prevalence of health care–associated infections in US hospitals.
      ,
      European Centre for Disease Prevention and Control
      Point prevalence survey of healthcare associated infections and antimicrobial use in European acute care hospitals.
      ,
      • Magill S.S.
      • Edwards J.R.
      • Bamberg W.
      • Beldavs Z.G.
      • Dumyati G.
      • Kainer M.A.
      • et al.
      Multistate point-prevalence survey of health care-associated infections.
      ], this infection has received little attention to date.
      Point prevalence studies (PPS) in Europe and the United States highlight the type and proportion of different HAIs. Data from Europe identified HAP as the most frequent HAI in prevalence studies conducted in England, Northern Ireland, Scotland, Wales [
      European Centre for Disease Prevention and Control
      Point prevalence survey of healthcare associated infections and antimicrobial use in European acute care hospitals.
      ] and Switzerland [
      • Metsini A.
      • Vazquez M.
      • Sommerstein R.
      • Marschall J.
      • Voide C.
      • Troillet N.
      • et al.
      Point prevalence of healthcare-associated infections and antibiotic use in three large Swiss acute-care hospitals.
      ]. In 2015, a multi-site PPS conducted in the United States also identified pneumonia as the most common HAI, with a prevalence of 26% [
      • Magill S.S.
      • O'Leary E.
      • Janelle S.J.
      • Thompson D.L.
      • Dumyati G.
      • Nadle J.
      • et al.
      Changes in prevalence of health care–associated infections in US hospitals.
      ]. Thirty-five percent of the pneumonia cases were classified as ventilator-associated pneumonia (VAP) and 65% as non-ventilator-associated hospital-acquired pneumonia (NV-HAP) [
      • Magill S.S.
      • O'Leary E.
      • Janelle S.J.
      • Thompson D.L.
      • Dumyati G.
      • Nadle J.
      • et al.
      Changes in prevalence of health care–associated infections in US hospitals.
      ], the two subcategories of HAP. A common definition of VAP is where a case of pneumonia where the patient is on mechanical ventilation for >2 calendar days on the date of event and the ventilator was in place on the date of event or the day before, other cases being considered NV-HAP [
      Centres of Disease Control and Prevention
      Pneumonia (ventilator -associated [VAP] and non-ventilator -associated pneumonia [PNEU]) event.
      ].
      While the impact of both VAP and NV-HAP on healthcare services and patients is significant, evidence suggests that NV-HAP occurs more frequently, is associated with higher healthcare costs and is equally as dangerous as VAP [
      • Davis J.
      • Finley E.
      The breadth of hospital-acquired pneumonia: nonventilated versus ventilated patients in Pennsylvania.
      ]. Findings from a multi-centred study from the United States suggests that 18.8% of patients with NV-HAP required transfer into the intensive care unit [
      • Baker D.
      • Quinn B.
      Hospital acquired pneumonia prevention initiative-2: incidence of nonventilator hospital-acquired pneumonia in the United States.
      ]. NV-HAP also results in a prolonged hospital stay and increased patient morbidity and mortality [
      • Micek S.T.
      • Chew B.
      • Hampton N.
      • Kollef M.H.
      A case-control study assessing the impact of nonventilated hospital-acquired pneumonia on patient outcomes.
      ,
      • Giuliano K.K.
      • Baker D.
      • Quinn B.
      The epidemiology of nonventilator hospital-acquired pneumonia in the United States.
      ]. However, NV-HAP is both underreported and understudied with most research conducted on VAP, thereby prompting recent calls for an urgent need to prioritise research on NV-HAP [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ]. This paper therefore focuses on NV-HAP, rather than VAP.
      Risk factors for the development of NV-HAP are quite varied and similar to those for HAP in general [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ]. Some identified risk factors include age (>70 years), male sex, length of hospital stay, multiple comorbidities, dysphagia and chronic obstructive pulmonary disease [
      • Micek S.T.
      • Chew B.
      • Hampton N.
      • Kollef M.H.
      A case-control study assessing the impact of nonventilated hospital-acquired pneumonia on patient outcomes.
      ,
      • Walter J.
      • Haller S.
      • Quinten C.
      • Kärki T.
      • Zacher B.
      • Eckmanns T.
      • et al.
      Healthcare-associated pneumonia in acute care hospitals in European Union/European Economic Area countries: an analysis of data from a point prevalence survey, 2011 to 2012.
      ,
      • Pássaro L.
      • Harbarth S.
      • Landelle C.
      Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a narrative review.
      ,
      • Sopena N.
      • Heras E.
      • Casas I.
      • Bechini J.
      • Guasch I.
      • Pedro-Botet M.L.
      • et al.
      Risk factors for hospital-acquired pneumonia outside the intensive care unit: a case-control study.
      ]. In some cases, patients may also present with few to no risk factors [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ]. Poor oral hygiene associated with dental plaque build up has also been identified as an important risk factor [
      • Kanzigg L.A.
      • Hunt L.
      Oral health and hospital-acquired pneumonia in elderly patients: a review of the literature.
      ], with identical genetic profiles found between respiratory pathogens isolated from dental plaque and bronchoalveolar lavage fluid [
      • Heo S.-M.
      • Haase E.M.
      • Lesse A.J.
      • Gill S.R.
      • Scannapieco F.A.
      Genetic relationships between respiratory pathogens isolated from dental plaque and bronchoalveolar lavage fluid from patients in the intensive care unit undergoing mechanical ventilation.
      ]. Various studies have demonstrated the benefits of implementing comprehensive oral care management protocols in reducing the incidence of NV-HAP [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ,
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ,
      • Munro S.
      • Baker D.
      Reducing missed oral care opportunities to prevent non-ventilator associated hospital acquired pneumonia at the department of veterans affairs.
      ,
      • Talley L.
      • Lamb J.
      • Harl J.
      • Lorenz H.
      • Green L.
      HAP prevention for nonventilated adults in acute care: can a structured oral care program reduce infection incidence?.
      ], highlighting the potential health and financial gains that could result from widespread implementation of such strategies for this problematic HAI [
      • Pássaro L.
      • Harbarth S.
      • Landelle C.
      Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a narrative review.
      ,
      • Pedersen P.U.
      • Larsen P.
      • Håkonsen S.J.
      The effectiveness of systematic perioperative oral hygiene in reduction of postoperative respiratory tract infections after elective thoracic surgery in adults: a systematic review.
      ]. Previous reviews have indicated that interventions that target potential modifiable risk factors may reduce NV-HAP, including improved oral hygiene, hand hygiene, early mobilisation, identification and appropriate management of dysphagia particularly in post-stroke patients, and prevention of viral infections [
      • Pássaro L.
      • Harbarth S.
      • Landelle C.
      Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a narrative review.
      ,
      • Pedersen P.U.
      • Larsen P.
      • Håkonsen S.J.
      The effectiveness of systematic perioperative oral hygiene in reduction of postoperative respiratory tract infections after elective thoracic surgery in adults: a systematic review.
      ]. We present a contemporary review, which seeks to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used. Based on this, we will present key gaps in the literature and methodological considerations to inform future interventional studies.

      Methods

      A systematic review to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities was undertaken. Reporting of this systematic review complied with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • The P.G.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ].

      Search strategy

      We performed a systematic search of the literature. Using the key words stated below, we searched the electronic database Medline and reviewed the reference lists of eligible articles to identify any additional relevant articles. The electronic search was limited to articles published between 1st January 1998 and 31st August 2018 in peer-reviewed journals, with no limits placed on language. A combination of Medical Subject Heading (MeSH) and free-text terms was used, based on a prior review of the literature [
      • Pássaro L.
      • Harbarth S.
      • Landelle C.
      Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a narrative review.
      ].
      The first search involved the following terms: (‘pneumonia’ OR ‘respiratory tract infection’ OR ‘respiratory infection’) AND (‘nosocomial’ OR ‘hospital-acquired’ OR ‘healthcare associated’ OR ‘healthcare-associated’) AND (‘prevention’). We performed an additional search and combined this with the results from the previous search.
      The keywords used in the second search were (‘pneumonia’ OR ‘respiratory tract infection’ OR ‘respiratory infection’) AND (‘nosocomial’ OR ‘hospital-acquired’ OR ‘healthcare associated’ OR ‘healthcare-associated’) AND.
      • ‘hand hygiene’ OR ‘hand washing’ OR
      • ‘oral care’ OR ‘oral hygiene’ OR ‘oral decontamination’ OR ‘oral health’ OR ‘mouthwashes’
      • ‘bed position’ OR ‘head position’ OR ‘body position’ OR ‘bed rest’ OR ‘bed protocol’
      • ‘mobilization’ OR ‘mobility’ OR ‘motility’ OR ‘physical activity’ OR ‘physiotherapy’
      • ‘dysphagia’ OR ‘swallowing’ OR ‘swallowing disorder’ OR ‘aspiration’ OR ‘aspirative’
      • ‘viral infection’ OR ‘viral’ OR ‘virus’ OR ‘flu’
      • ‘stress bleeding prophylaxis’ OR ‘gastric’ OR ‘gastric protection’ OR ‘acid-suppressive therapy’ OR ‘acid-suppressive’ OR ‘proton pump inhibitor’ OR ‘omeprazole’ OR ‘ranitidine’

      Selection criteria

      The inclusion criteria were all randomised controlled trials and observational studies (cohort, case control, observational, cross sectional or case/short reports) that examined measures (excluding vaccination and systematic antimicrobial therapy) to reduce HAP in hospitals and aged-care facilities. Only studies examining adult populations were included. Studies that did not analyse the effect of any prevention measure were initially included but subsequently removed for sub-analysis. Exclusion criteria were studies examining VAP, all grey literature, non-peer-reviewed literature, reviews, editorials and commentaries.

      Definitions

      For the purpose of this systematic review, we used the following definitions:
      • ‘Healthcare-associated infection’ refers to any infection as defined or accepted by the authors as being healthcare-associated, hospital-acquired or nosocomial.
      • ‘Measure’ refers to interventions, clinical practice or policy. It excludes systematic antimicrobial treatment and vaccination measures.
      • We accepted the definitions and application of defining pneumonia as stated in the paper.

      Study selection

      We examined and assessed the titles and abstracts of all the publications identified in the electronic database for relevance and appropriateness to the review question and excluded those that were irrelevant. Of the remaining articles, we reviewed the full texts to assess their further eligibility. Articles deemed to have data relevant to the systematic review were included. Trained research assistants performed the study selection process and other stages of the review. Ten percent of the original articles were cross-checked with the study eligibility criteria by two of the research assistants. In addition, an experienced research member randomly selected 10% of the original articles retrieved in the initial search and reviewed them as a cross-check against the study eligibility criteria. Two members of the research team resolved any discrepancies that were observed in the application of either the inclusion or the exclusion criteria.

      Data extraction

      For each eligible study, the following data were extracted using a data extraction form developed in Excel (Microsoft, USA): author(s); year of publication; country of study; study design; study population; sample; setting; outcome measures; results for both the control and intervention groups, and conclusions. All data extracted were cross-checked by a second member of the team. We did not attempt to contact the authors of papers that contained missing data or unclear information.

      Risk of bias

      An assessment of the study quality and risk of bias in the articles included in the review was conducted using the Newcastle–Ottawa Scale [
      • Higgins Julian P.T.
      • Green Sally
      Cochrane handbook for systematic reviews of interventions.
      ,
      • Wells G.
      • Shea B.
      • O'connell D.
      • Peterson J.
      • Welch V.
      • Losos M.
      • et al.
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis.
      ]. The Newcastle–Ottawa Scale, is a collaboration between several universities, to assess the quality of studies with its design, content and ease of use directed to the task of incorporating the quality assessments. The scales uses a ‘star system’ to judge articles in three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively [
      Ottawa Hospital Research Institute
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
      ]. A maximum of nine stars to be awarded to a study. The content validity and inter-rater reliability of this tool have been established [
      • Wells G.
      • Shea B.
      • O'connell D.
      • Peterson J.
      • Welch V.
      • Losos M.
      • et al.
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis.
      ]. One researcher undertook this assessment independently, with a random 10% of the articles reviewed by a second researcher. There were no discrepancies in the application of the risk of bias assessment found, when the random sample of articles was compared by a second reviewer.

      Data analysis

      Extracted data from the included studies were synthesised and summarised in evidence tables. Given the significant heterogeneity in the included studies, we did not attempt to conduct a meta-analysis.

      Results

      Overview

      The literature search yielded 1551 articles. Of these, 56 articles remained for a full text review following a review of the titles and abstracts and the exclusion of duplicates. After screening the 56 articles against the study's inclusion and exclusion criteria, we excluded 43 articles either because they did not report on NV-HAP, they did not evaluate the impact of an intervention, or they were reviews. With the addition of three eligible articles that were known to the research team from manual searches (one from an excluded review, two from references lists of included articles), 15 articles met the inclusion criteria and were included in the final systematic review (Fig. 1).
      Figure 1
      Figure 1Flow diagram for selection of articles.
      In this review of literature, we identified 15 studies that involved an intervention aimed at reducing NV-HAP. There was considerable heterogeneity in these studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management.

      Study characteristics

      Table 1 provides an overview of the 15 studies included in the review. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9), with four oral care approaches using dental professionals [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ,
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ]. Three studies evaluated a form of physical activity, such as passive movements [
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ,
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ,
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ]; two studies used dysphagia screening and management [
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ,
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ]; and another study evaluated prophylactic antibiotics [
      • Johansen N.J.
      • Hahn C.H.
      Prophylactic antibiotics at the time of tracheotomy lowers the incidence of pneumonia.
      ]. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials.
      Table 1Studies included in the review.
      Author, YearDesignSampleSettingBroad intervention strategySignificant change in pneumonia
      Adachi et al., 2002
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      RCT141Nursing homeOral care (professional)YES
      Bellisimo-Rodrigues et al., 2014
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      RCT254Hospital (Intensive Care Unit)Oral care (professional)YES
      Boden et al., 2018
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      RCT441HospitalPhysical activityYES
      Bouringault et al., 2010
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      RCT2513Nursing homeOral care (professional)NO
      Chen et al., 2016
      • Chen Y.
      • Mao E.‐Q.
      • Yang Y.‐J.
      • Zhao S.‐Y.
      • Zhu C.
      • Wang X.‐F.
      • et al.
      Prospective observational study to compare oral topical metronidazole versus 0.2% chlorhexidine gluconate to prevent nosocomial pneumonia.
      Cohort873Hospital (Intensive Care Unit)Oral careYES
      Cuesy et al., 2010
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      RCT223HospitalPhysical activityYES
      Johansen et al., 2016
      • Johansen N.J.
      • Hahn C.H.
      Prophylactic antibiotics at the time of tracheotomy lowers the incidence of pneumonia.
      Cohort88Hospital (Ear, Nose and Throat Department)Prophylactic antibioticsYES
      McNally et al., 2018
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      Quasi-experimental2891Hospital (non-ICU)Oral careNO
      Quinn et al., 2014
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      Quasi-experimentalHospitalOral careDecrease+
      Robertson et al., 2013
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      Quasi-experimental85Hospital (acute neurosurgical unit)Oral careYES
      Schrock et al., 2018
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      Cohort2372HospitalDysphagia screenYES
      Stolbrink et al., 2014
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      Quasi-experimental156Hospital (respiratory and elderly wards)Physical activityYES
      Titsworth et al., 2013
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      Cohort2334HospitalDysphagia screenYES
      Wagner et al., 2016
      • Wagner C.
      • Marchina S.
      • Deveau J.A.
      • Frayne C.
      • Sulmonte K.
      • Kumar S.
      Risk of stroke-associated pneumonia and oral hygiene.
      Cohort1656HospitalOral careYES
      Yoneyama et al., 2012
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      RCT366Nursing HomeOral care (professional)NO
      Note: + significance values not provided.

      Risk of bias assessment

      We undertook a risk of bias assessment on the 15 studies included in the review. The maximum star rating using the Newcastle–Ottawa Scale is nine stars. Four studies received a star rating of eight [
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ,
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ,
      • Johansen N.J.
      • Hahn C.H.
      Prophylactic antibiotics at the time of tracheotomy lowers the incidence of pneumonia.
      ,
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ], six studies received a rating of seven [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ,
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ,
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ,
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ,
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ,
      • Wagner C.
      • Marchina S.
      • Deveau J.A.
      • Frayne C.
      • Sulmonte K.
      • Kumar S.
      Risk of stroke-associated pneumonia and oral hygiene.
      ] and five studies received a rating of five or less [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ,
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ,
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ,
      • Chen Y.
      • Mao E.‐Q.
      • Yang Y.‐J.
      • Zhao S.‐Y.
      • Zhu C.
      • Wang X.‐F.
      • et al.
      Prospective observational study to compare oral topical metronidazole versus 0.2% chlorhexidine gluconate to prevent nosocomial pneumonia.
      ]. Table 2 provides an overview of the risk of bias assessment for each study.
      Table 2Risk of bias assessment.
      First AuthorYearElements of Newcastle–Ottawa Scale
      Selection (0–4)Comparability (0–2)Exposure (0–3)Total stars
      Adachi20024004
      Bellisimo-Rodrigues20142237
      Boden20182237
      Bourigaulta20104105
      Chen20163025
      Cuesy20103137
      Johansen20163238
      McNally20183238
      Quinn20142035
      Robertson20134037
      Schrock20183025
      Stolbrink20143227
      Titsworth20134228
      Wagner20163227
      Yoneyama20024138

      Oral care and NV-HAP prevention

      Nine studies in this review involved an oral care intervention to reduce the incidence of NV-HAP. Four of the nine studies involved professional oral care, such as oral care provided by a dentist or hygienist. All of these studies were randomised controlled studies [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ,
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ], and three of them were performed in nursing homes [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ,
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ]. The remainder of the studies (n = 5), did not use professional dental care as part of the oral care intervention [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ,
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ,
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ,
      • Wagner C.
      • Marchina S.
      • Deveau J.A.
      • Frayne C.
      • Sulmonte K.
      • Kumar S.
      Risk of stroke-associated pneumonia and oral hygiene.
      ,
      • Chen Y.
      • Mao E.‐Q.
      • Yang Y.‐J.
      • Zhao S.‐Y.
      • Zhu C.
      • Wang X.‐F.
      • et al.
      Prospective observational study to compare oral topical metronidazole versus 0.2% chlorhexidine gluconate to prevent nosocomial pneumonia.
      ]. None of these five studies used a randomised controlled design.

      Non-professional oral care

      There was considerable heterogeneity among interventions in the studies that involved routine oral care (i.e. non-professional dental care). No two studies had the same intervention, and where an antiseptic was used as part of oral care, the type of antiseptic differed between studies. The interventions included: oral care kits that contained an antiseptic (cetylpyridinium chloride and 1.5% hydrogen peroxide) [
      • Wagner C.
      • Marchina S.
      • Deveau J.A.
      • Frayne C.
      • Sulmonte K.
      • Kumar S.
      Risk of stroke-associated pneumonia and oral hygiene.
      ]; oral care by swabbing with an antiseptic (chlorhexidine gluconate vs. metronidazole) [
      • Chen Y.
      • Mao E.‐Q.
      • Yang Y.‐J.
      • Zhao S.‐Y.
      • Zhu C.
      • Wang X.‐F.
      • et al.
      Prospective observational study to compare oral topical metronidazole versus 0.2% chlorhexidine gluconate to prevent nosocomial pneumonia.
      ]; increased volume of oral care and the use of an antiseptic (0.05% cetylpyridinium chloride) [
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ]; oral care kits and the use of a toothbrush containing sodium bicarbonate and an antiseptic (antiseptic unspecified) [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ]; and moisturiser, toothbrushes and oral swabs impregnated with sodium bicarbonate and an antiseptic rinse (1.5% hydrogen peroxide) [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ]. The outcomes from the oral care interventions were largely associated with a reduction in NV-HAP (Table 3).
      Table 3Summary of findings involving oral care and healthcare associated pneumonia.
      Study (first author)OutcomeIntervention (n)Control (n)Comments
      EventTotalEventTotal
      Professional dental care
      AdachiFatal aspiration pneumonia240848Significant reduction (p < 0.05). Original sample = 141, participants lost to follow-up. Observed over 24 month period.
      Bellisimo-RodriguesPneumonia in non-ventilated patients01271127No cases during intervention. 294 sample, 40 excluded as died or discharged from ICU within 48 h. Pneumonia in non-ventilated patients was secondary outcome.
      YoneyamaPneumonia2118434182Significant reduction (p < 0.05). 51 participants excluded from analysis because they died from causes other than pneumonia during follow-up.
      Fatal pneumonia1418430182Significant reduction (p < 0.05)
      BourigaultPatients with pneumonia938682031645No difference
      Fatal pneumonia15868261645No difference
      Non-professional dental care
      ChenHospital acquired pneumonia8466144212Significant reduction (p < 0.05)
      McNallyHospital acquired pneumonia251403261487No difference
      QuinnHospital acquired pneumoniaUnclearUnclearUnclearUnclearIncidence decreased from 0.49 to 0.3 per 1000 patient days (38.8%).
      RobertsonHospital acquired pneumonia2321351Significant reduction (p < 0.05)
      WagnerHospital acquired pneumonia (post-stroke)9894999707Significant reduction (p < 0.05)
      Note: The raw numerator and denominator data from this study in the pre and post intervention phases are not able to be extracted from this study. No confident intervals are provided around the incidence rates.

      Professional oral care

      Four studies involved the use of a dentist or dental hygienist in the delivery of oral care [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ,
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ]. The interventions in the studies included.
      • Dental hygienists performed professional oral health care weekly [
        • Adachi M.
        • Ishihara K.
        • Abe S.
        • Okuda K.
        • Ishikawa T.
        Effect of professional oral health care on the elderly living in nursing homes.
        ]
      • dental care provided by a dental surgeon, 4–5 times a week [
        • Bellissimo-Rodrigues W.T.
        • Menegueti M.G.
        • Gaspar G.G.
        • Nicolini E.A.
        • Auxiliadora-Martins M.
        • Basile-Filho A.
        • et al.
        Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
        ] Patients receiving dental care were compared to those receiving routine oral care.
      • annual visit to the dentist, tooth, tongue and mucosa brushing three times a day and after each meal [
        • Bourigault C.
        • Lietard C.
        • Golmard J.L.
        • Maman L.
        • Nabet C.
        • Carrat F.
        • et al.
        Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
        ] In addition, those receiving the intervention received used an chlorhexidine mouth wash.
      • annual visit to the dentist, tooth, tongue and mucosa brushing three times a day and after each meal [
        • Yoneyama T.
        • Yoshida M.
        • Ohrui T.
        • Mukaiyama H.
        • Okamoto H.
        • Hoshiba K.
        • et al.
        Oral care reduces pneumonia in older patients in nursing homes.
        ]
      Two of the four studies identified a reduction in NV-HAP associated with the intervention (Table 3) [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ]. One study recorded no cases of NV-HAP during the intervention phase [
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ], while the fourth and largest study did not identify a reduction in NV-HAP [
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ].

      Dysphagia and NV-HAP prevention

      Two non-randomised studies used dysphagia screening as the primary method for NV-HAP prevention [
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ,
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ]. Schrock and colleagues used a pre-post quasi-experimental study to evaluate rates of NV-HAP in patients with ischemic and haemorrhagic stroke both before and after the use of a dysphagia screen [
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ]. In the post study phase, a dysphagia screening test was applied to all acute stroke patients in the emergency department. For patients In the haemorrhagic group, the incidence of NV-HAP decreased from 19% to 15% (P < 0.001), while in the ischemic stroke groups, NV-HAP rates decreased from 13.8% to 8% (P = 0.007) [
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ]. Titsworth et al. also examined an intervention in patients with ischemic or haemorrhagic stroke [
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ]. The intervention was a nurse-led bedside dysphagia screen and a rapid clinical swallow undertaken by a speech pathologist. The authors suggest that this quality improvement initiative coincided with a reduction in NV-HAP from 6.5% to 2.8% among the stroke patients (P < 0.001) [
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ].

      Mobility and NV-HAP prevention

      We identified three studies that involved a form of physical activity as a way of reducing the incidence of NV-HAP [
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ,
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ,
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ]. Cuesy et al. conducted a randomised controlled trial examining the effect of turning and passive mobilisation on patients with acute ischemic stroke [
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ]. The turn-mob program, instigated during the intervention phase, included modifying the patient from supine position to right and left lateral recumbent position every 2 h, in addition to passive mobilizations of the 4 limbs through each segment's entire range of motion, every 6 h. Family members were also involved in this process. The intervention was associated with a decrease in NV-HAP (relative risk of 0.39; 95% CI 0.19–0.79; P = 0.008) [
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ]. A randomised controlled trial undertaken by Boden et al. also reported a reduction in NV-HAP [
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ]. The intervention included pre-operative patient education, early ambulation and self-directed breathing exercises, and additional pre-operative physiotherapy. Although the primary outcome was post-operative pulmonary complications, a reduction in NV-HAP was also identified (HR 0.45; 95% CI 0.26–0.78, P = 0.005) [
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ]. Stolbrink et al. also undertook a physiotherapy-based intervention that involved early mobilisation in patients following a hip fracture [
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ]. In this quasi-experimental study, the intervention was associated with a lower incidence of NV-HAP (HR 0.39; 95% CI 0.22–0.68; P = 0.001) [
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ].

      Differences in NV-HAP definitions used in included articles

      The articles included in this review used different definitions for determining cases of NV-HAP. These included chest radiography with clinical symptoms of pneumonia [
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ,
      • Boden I.
      • Skinner E.H.
      • Browning L.
      • Reeve J.
      • Anderson L.
      • Hill C.
      • et al.
      Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.
      ,
      • Cuesy P.G.
      • Sotomayor P.L.
      • Piña J.O.T.
      Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program.
      ,
      • Stolbrink M.
      • McGowan L.
      • Saman H.
      • Nguyen T.
      • Knightly R.
      • Sharpe J.
      • et al.
      The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.
      ,
      • Schrock J.W.
      • Lou L.
      • Ball B.A.W.
      • Van Etten J.
      The use of an emergency department dysphagia screen is associated with decreased pneumonia in acute strokes.
      ], Administrative coding data [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ,
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ,
      • Wagner C.
      • Marchina S.
      • Deveau J.A.
      • Frayne C.
      • Sulmonte K.
      • Kumar S.
      Risk of stroke-associated pneumonia and oral hygiene.
      ], Clinical Pulmonary Infection Score [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ], Centers for Disease Control and Prevention (CDC) definition [
      • Bellissimo-Rodrigues W.T.
      • Menegueti M.G.
      • Gaspar G.G.
      • Nicolini E.A.
      • Auxiliadora-Martins M.
      • Basile-Filho A.
      • et al.
      Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.
      ,
      • Titsworth W.L.
      • Abram J.
      • Fullerton A.
      • Hester J.
      • Guin P.
      • Waters M.F.
      • et al.
      Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke.
      ], and national professional guidelines [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ]. Some articles were less clear or did not specify the diagnostic approach [
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ,
      • Bourigault C.
      • Lietard C.
      • Golmard J.L.
      • Maman L.
      • Nabet C.
      • Carrat F.
      • et al.
      Impact of bucco-dental healthcare on the prevention of pneumonia in geriatrics: a cluster-randomised trial.
      ].

      Discussion

      In this review, interventions from studies aimed at reducing NV-HAP, appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management. The most common preventive strategy used to reduce NV-HAP was oral care. The studies included in our review focussed on improving oral care through education, increasing frequency and or consistency of oral care provided and use of an antiseptic. Further, the highest quality studies evaluating the impact of improved oral care all utilised professionals in the field of dentistry, such as dentists and/or dental hygienists. However, while most of these studies were randomised controlled trials, they were largely conducted in residential aged care facilities, with only one randomised controlled study conducted in a hospital setting. The feasibility of implementing an intervention requiring dentistry input in a hospital setting is limited at best. There are challenges in improving the provision of oral care in the hospital setting. A recent study illustrated this with an average of 1.6 tooth brushings per day, when the goal of the intervention was three per day by the nursing staff [
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ]. A recent review also identified variation in the reported frequency of oral care provided by nurses (range 2–3.5 times a day) and the documented frequency of oral care in nursing notes (range 1.2–3.5 times a day) for non-ventilated patients [
      • Emery K.P.
      • Guido-Sanz F.
      Oral care practices in non-mechanically ventilated intensive care unit patients: an integrative review.
      ]. Further, the lack of nurse-led randomised studies for NV-HAP prevention identified in this review highlights a critical issue for patient care. As nurses are primarily responsible for the daily care needs of patients, they have a vital role to play in the prevention of HAIs, including NV-HAP [
      • Collins A.S.
      Preventing health care–associated infections.
      ]. Three studies, Quinn et al. [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ], McNally et al. [
      • McNally E.
      • Krisciunas G.P.
      • Langmore S.E.
      • Crimlisk J.T.
      • Pisegna J.M.
      • Massaro J.
      Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research.
      ] and Robertson et al. [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ], all emphasised the importance of nurse-led initiatives along with interdisciplinary collaboration as being vital to successful oral care interventions. Improvements in oral care are considered a modifiable risk factor for NV-HAP [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ,
      • Tablan O.C.
      • Anderson L.J.
      • Besser R.
      • Bridges C.
      • Hajjeh R.
      Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the healthcare infection control practices advisory committee.
      ].
      The differing antiseptic agents used as part of oral care interventions in the studies included in this review also warrant discussion, as uncertainty remains regarding the most appropriate antiseptic for oral care in the prevention of NV-HAP. Antiseptic agents such as chlorhexidine gluconate, sodium bicarbonate, hydrogen peroxide and cetylpyridinium chloride are examples of antiseptics that were used in the included studies. Povidone-iodine is also an antiseptic agent known to be used for oral care in the prevention of HAP in general [
      • Labeau S.O.
      • Van de Vyver K.
      • Brusselaers N.
      • Vogelaers D.
      • Blot S.I.
      Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis.
      ]. Findings from our review do not add to the existing evidence base regarding the use of chlorhexidine gluconate in oral care for the prevention of pneumonia in the literature [
      • Tablan O.C.
      • Anderson L.J.
      • Besser R.
      • Bridges C.
      • Hajjeh R.
      Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the healthcare infection control practices advisory committee.
      ,
      • Vogelaers D.
      • Deschepper M.
      • Blot S.
      Oral care with chlorhexidine gluconate: time to focus on outcomes that matter.
      ,
      • Torres A.
      • Niederman M.S.
      • Chastre J.
      • Ewig S.
      • Fernandez‐Vandellos P.
      • Hanberger H.
      • et al.
      International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).
      ,
      • Kalil A.C.
      • Metersky M.L.
      • Klompas M.
      • Muscedere J.
      • Sweeney D.A.
      • Palmer L.B.
      • et al.
      Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.
      ]. Further research on the effectiveness of chlorhexidine and other antiseptics for oral care in HAP prevention has been called for, including cost effectiveness analyses [
      • Tablan O.C.
      • Anderson L.J.
      • Besser R.
      • Bridges C.
      • Hajjeh R.
      Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the healthcare infection control practices advisory committee.
      ,
      • Torres A.
      • Niederman M.S.
      • Chastre J.
      • Ewig S.
      • Fernandez‐Vandellos P.
      • Hanberger H.
      • et al.
      International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).
      ].
      Our review also identified dysphagia screening and physical activity or movement, as effective strategies for preventing NV-HAP. This supports findings from a narrative review of the literature by Pássaro et al. [
      • Pássaro L.
      • Harbarth S.
      • Landelle C.
      Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a narrative review.
      ], which also showed a reduction in NV-HAP following the use of early mobilization interventions as well as prompt diagnosis and treatment of dysphagia. However, given the lack of studies assessing these strategies in patients with NV-HAP (two studies for dysphagia and three for physical activity) and the lack of randomised control designs, their effectiveness is uncertain, thus suggesting the need for further evaluation of these strategies.
      The diversity of interventions used for NV-HAP prevention and settings makes comparisons, generalisability and translation into practice difficult. In addition, the small sample size of published studies [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ,
      • Adachi M.
      • Ishihara K.
      • Abe S.
      • Okuda K.
      • Ishikawa T.
      Effect of professional oral health care on the elderly living in nursing homes.
      ] poses a limitation to the generalisability of the findings. Hence, the challenges in designing future NV-HAP intervention studies include diagnoses, adequate sample sizes and ethical considerations around accessing a high-risk population. As noted in our review, the methods used to diagnose NV-HAP varied and included definitions from the CDC guidelines [
      • Quinn B.
      • Baker D.L.
      • Cohen S.
      • Stewart J.L.
      • Lima C.A.
      • Parise C.
      Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
      ], Association of Medical Microbiology and Infectious Diseases Canada guidelines [
      • Robertson T.
      • Carter D.
      Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients.
      ], clinical symptoms and signs, and radiological features [
      • Yoneyama T.
      • Yoshida M.
      • Ohrui T.
      • Mukaiyama H.
      • Okamoto H.
      • Hoshiba K.
      • et al.
      Oral care reduces pneumonia in older patients in nursing homes.
      ]. While it is recognised that there is no gold standard for the diagnosis of NV-HAP or VAP [
      • Kalil A.C.
      • Metersky M.L.
      • Klompas M.
      • Muscedere J.
      • Sweeney D.A.
      • Palmer L.B.
      • et al.
      Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.
      ], we suggest that future studies should use NV-HAP definitions from point prevalence studies, such as the European Centre for Disease Prevention and Control [
      European Centre for Disease Prevention and Control
      Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals – protocol version 5.3.
      ]. The use of standard definitions allows infection control and prevention professionals and hospital epidemiologists to make sensible comparisons among data from hospitals or against national data [
      • Collins A.S.
      Preventing health care–associated infections.
      ]. The use of definitions that are already familiar from current use may also improve the reliability of their application in studies.
      While HAP is one of the most prevalent HAIs among hospitalised patients, the incidence of NV-HAP in hospitalised patients is relatively low [
      • Baker D.
      • Quinn B.
      Hospital acquired pneumonia prevention initiative-2: incidence of nonventilator hospital-acquired pneumonia in the United States.
      ]. Hence, a large sample size providing sufficient statistical power will be required for any study seeking to determine the effects of NV-HAP interventions. This large sample size, coupled with both the need to undertake prospective diagnoses and difficulties in implementing oral care interventions, presents a major challenge. The incidence of NV-HAP is higher in high-risk groups, such as the elderly or those with multiple co-morbidities; therefore, studying this type of group may aid a reduction in sample size. However, the challenge with studying this type of group pertains to informed consent and the associated selection bias. Therefore, a stepped wedge design may be a useful study design for future NV-HAP studies [
      • Prost A.
      • Binik A.
      • Abubakar I.
      • Roy A.
      • De Allegri M.
      • Mouchoux C.
      • et al.
      Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies.
      ].
      Our review has several limitations. The variability in the definitions of NV-HAP and the substantial clinical and methodological heterogeneity between the included studies made it impossible to undertake a meta-analysis. The quality and risk of bias of one-third of the studies included in the review had ratings of five or less, and therefore were considered to have a high risk of bias and the potential to impact the study findings. In view of the findings from this paper, it appears that improving the quality and frequency of oral care, in addition to mobilisation may be useful interventions in reducing the incidence of NV-HAP. Nurse led randomised studies, to assess the effectiveness of an intervention or interventions to reduce the incidence of NV-HAP are required. Such studies need to be rigorously conducted and sufficiently powered.

      Authorship statement

      BM, PR, AC and AS conceived this study. HR, SC, SR contributed to data collection. All authors reviewed the manuscript and provided critical input. All authors approved the final version of this paper. BM was the lead for this project.

      Conflict of interest

      Three of the authors have an editorial affiliation with the journal. They played no role whatsoever in the peer review process or decisions relating to this manuscript.

      Funding

      This study did not receive a grant or external funding to support its conduct.

      Provenance and peer review

      Not commissioned; externally peer reviewed.

      Ethics

      Not required, this is a systematic review of the literature.

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