Systematic Reviews Pre-admission interventions to improve outcome after elective surgery - protocol for a systematic review --Manuscript Draft-Manuscript Number: Full Title:
Pre-admission interventions to improve outcome after elective surgery - protocol for a systematic review
Article Type:
Protocol
Funding Information:
Wellcome Trust Dr Maria Pufulete (Elizabeth Blackwell Institute Research for Health Scheme 2014)
Abstract:
Abstract Background Poor physical health and fitness increases the risk of death and complications after major elective surgery. Pre-admission interventions to improve patients' health and fitness (referred to as prehabilitation) may reduce postoperative complications, decrease the length of hospital stay and facilitate the patient's recovery. We will conduct a systematic review of randomised controlled trials (RCTs) to examine the effectiveness of different types of prehabilitation interventions in improving the surgical outcomes of patients undergoing elective surgery. Methods This review will be conducted and reported according to the Cochrane and PRISMA reporting guidelines. MEDLINE, EMBASE, CENTRAL, CINAHL, PsychINFO, ISI Web of Science and clinical trial registers will be searched for any intervention administered before any elective surgery (including physical activity, nutritional, educational, psychological, clinical or multicomponent), which aims to improve postoperative outcomes. Reference lists of included studies will be searched and grey literature including conference proceedings, theses, dissertations, and preoperative assessment (POA) protocols will be examined. Study quality will be assessed using Cochrane's risk of bias tool, and meta-analyses for trials that use similar interventions and report similar outcomes will be undertaken where possible. Discussion This systematic review will determine whether different types of interventions administered before elective surgery are effective in improving postoperative outcomes. It will also determine which components or combinations of components would form the most effective prehabilitation intervention. Systematic review registration: PROSPERO 2015: CRD42015019191
Corresponding Author:
Maria Pufulete, MSc, PhD University of Bristol Bristol, UNITED KINGDOM
Corresponding Author Secondary Information: Corresponding Author's Institution:
University of Bristol
Corresponding Author's Secondary Institution: First Author:
Rachel Perry, BA, MA, MPhil
First Author Secondary Information: Order of Authors:
Rachel Perry, BA, MA, MPhil Lauren Scott, BSc, MSc Alison Richards, MA (Hons) DiplLib Anne Haase, BA, MSc, PhD Jelena Savovic, MPharm, PhD, MSc Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
Andy Ness, BMedSci, BM,BS(Nott), DA, MRCP, MFPHM, FFPHM, PhD, Charlotte Atkinson, BSc, PhD Jessica Harris, BSc, MSc, PhD Lucy Culliford, BSc, PhD Sanjoy Shah, MD Maria Pufulete, MSc, PhD Order of Authors Secondary Information: Opposed Reviewers:
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Manuscript
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Pre-admission interventions to improve outcome after elective surgery –
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protocol for a systematic review
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Perry R2, Scott LJ1, Richards A3, Haase AM4, Savovic J3, Ness AR2, Atkinson C2,
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Harris J1, Culliford L1, Shah S5,Pufulete M1
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1
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Infirmary, Queen's Building, Bristol BS2 8HW, UK.
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Maudlin Street, Bristol BS1 2LY, UK.
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Clinical Trials and Evaluation Unit, University of Bristol, Level 7, Bristol Royal
Biomedical Research Unit in Nutrition Diet and Lifestyle, University of Bristol, Lower
NIHR CLAHRC West, University Hospitals Bristol NHS Foundation Trust, 9th Floor,
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Whitefriars, Lewins Mead, Bristol BS1 2NT, UK.
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Priory Road, Bristol BS8 1TZ, UK.
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5 Preoperative
Centre for Exercise, Nutrition and Health Sciences, School for Policy Studies, 8
Assessment Clinic, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
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*Correspondence to:
[email protected]
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Abbreviations
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CI, confidence interval; ERAS, enhanced recovery after surgery; RCT, randomised
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controlled trial; RR, risk ratio.
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Keywords:
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Prehabilitation, elective surgery, systematic review, physical activity, pre-operative
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nutrition, improving fitness before surgery.
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Abstract
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Background
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Poor physical health and fitness increases the risk of death and complications after
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major elective surgery. Pre-admission interventions to improve patients’ health and
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fitness (referred to as prehabilitation) may reduce postoperative complications,
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decrease the length of hospital stay and facilitate the patient’s recovery. We will
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conduct a systematic review of randomised controlled trials (RCTs) to examine the
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effectiveness of different types of prehabilitation interventions in improving the
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surgical outcomes of patients undergoing elective surgery.
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Methods
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This review will be conducted and reported according to the Cochrane and PRISMA
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reporting guidelines. MEDLINE, EMBASE, CENTRAL, CINAHL, PsychINFO, ISI
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Web of Science and clinical trial registers will be searched for any intervention
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administered before any elective surgery (including physical activity, nutritional,
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educational, psychological, clinical or multicomponent), which aims to improve
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postoperative outcomes. Reference lists of included studies will be searched and
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grey literature including conference proceedings, theses, dissertations, and
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preoperative assessment (POA) protocols will be examined. Study quality will be
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assessed using Cochrane’s risk of bias tool, and meta-analyses for trials that use
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similar interventions and report similar outcomes will be undertaken where possible.
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Discussion
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This systematic review will determine whether different types of interventions
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administered before elective surgery are effective in improving postoperative
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outcomes. It will also determine which components or combinations of components
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would form the most effective prehabilitation intervention. 2
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Systematic review registration: PROSPERO 2015: CRD42015019191
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Background
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Each year in England there are over 4.6 million hospital admissions that lead to
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surgical care [1]. Although mortality after elective surgery is low (about 1.4% for in
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hospital mortality [2] and about 0.4% for overall mortality [3]), surgery is an important
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cause of death owing to the large number of procedures. Furthermore, up to 75% of
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patients experience morbidity [3], which negatively influences quality of life.
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Surgery, anaesthesia and other perioperative interventions cause trauma to
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tissues and physiological disturbances. Patient outcome is influenced by the type
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and extent of surgical insult, patient susceptibility to postoperative harm and the
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quality of perioperative care, although increasing age, specific co-morbidities and
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patient fitness are also important factors [4]. Being unfit increases risk of death and
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complications after major surgery [5-7].
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Enhanced recovery after surgery (ERAS) programmes, also known as ‘fast-
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track surgery’, are now part of standard care pathways to improve postoperative
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outcomes [8]. However, improving patients’ fitness prior to surgery may also lead to
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more positive outcomes and reduce complications [9]. ‘Prehabilitation’ is a broad
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term that applies to any intervention administered before surgery which aims to
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improve a patient’s health and fitness in order to reduce surgery-related morbidity,
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decrease the length of hospital stay and facilitate the patient’s return to normal.
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Incorporating such interventions within standard ERAS programmes may further
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improve outcomes for surgical patients.
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Description of the intervention
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The optimal prehabilitation intervention has not been defined, but it is likely to be
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multicomponent, including exercise, diet, psychological and clinical components.
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Most prehabilitation interventions reported in the literature have focused on exercise
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regimens (endurance and strength training exercises) and have been administered
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in different populations awaiting elective surgery (including cardiac, cancer and
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orthopaedic). The studies reporting these exercise interventions are generally small
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and have varying results. Most have focused on patients undergoing elective
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orthopaedic surgery, who have an average waiting time of 18 weeks before surgery
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[10, 11]. In contrast, few studies have focused on cancer patients, for whom the
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time window to intervene is usually less than 6 weeks. The suitability of some
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interventions may therefore depend on the amount of time available prior to surgery.
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Interventions based on exercise alone may not be sufficient to enhance
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functional capacity if factors such as nutrition, anxiety, and perioperative care are not
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taken into consideration. More recent studies have included nutritional,
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psychological, educational and monitoring components in the prehabilitation
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intervention, to create a multicomponent intervention [12]. Additional components,
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such as smoking cessation, reducing alcohol intake and blood glucose control may
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also have the potential to improve surgical outcome and could therefore be part of
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multicomponent intervention.
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It is unclear which components or combinations of components would form
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the most effective (and cost effective) prehabilitation intervention. It is also unclear
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whether prehabilitation interventions can be generic (i.e. successfully used in all
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patients undergoing elective surgery of any type), or whether they need to be tailored
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to patients undergoing specific type of surgery (e.g. surgery for cancer). Patients
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diagnosed with potentially life-limiting conditions (such as cancer) have this
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emotional burden to deal with in addition to concerns about their surgery and
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recovery, so their care may need to have a more psychological element, for
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example.
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How the intervention might work
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Physical fitness, nutritional status, lifestyle factors such as smoking and pre-existing
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comorbidities are important prognostic factors for predicting adverse outcomes and
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mortality in surgical patients. Therefore assessing baseline status and taking steps
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to improve these risk factors should improve outcomes for surgical patients. The
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mechanisms for these processes will vary depending on the type of intervention; for
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example, exercise improves lung function so that the patient can increase their
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respiratory volume to cope with increased postoperative metabolic rate, elevated
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body temperature, possible infections, etc.
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Why is it important to do this review
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There is currently no consensus as to the optimal prehabilitation intervention. The
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term ‘prehabilitation’ has largely been used to refer to physical activity interventions,
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and existing systematic reviews have focused on this aspect. Currently there are
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five published systematic reviews [13-17] that have investigated various physical
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activity regimens on clinical outcomes and health related quality of life. Two reviews
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included RCTs only (6 to 8 studies) [13, 15] and three included both RCTs and non-
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RCTs (up to 21 studies) [14, 16, 17]. Patient populations for these reviews were
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patients undergoing all adult surgery (including orthopaedic surgery) [13, 16],
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elective major abdominal surgery (colorectal, liver, pancreatic, biliary) [15], cardiac,
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respiratory, or gastrointestinal surgery [14], and surgery for cancer [17]. There is
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also a published protocol for a systematic review registered with the PROSPERO
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international prospective register of systematic reviews, also focused on physical
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activity interventions in all adult surgical populations [18].
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A recent Cochrane systematic review assessed the effectiveness of pre-
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operative nutrition support in patients undergoing gastrointestinal surgery [19],
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including RCTs assessing the effect of nutritional formulas delivered by a parenteral
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route, enteral route, or oral supplements, most administered for 10 days pre-
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operatively. Thirteen RCTs were included in the review. Seven evaluated immune
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enhancing nutritional formulas (which reduced total post-operative complications,
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risk ratio (RR) 0.67, 95% confidence interval (CI) 0.53 to 0.84) and three evaluated
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parenteral nutrition (also showing a reduction in post-operative complications (RR
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0.64 95% CI 0.46 to 0.87), mainly in malnourished individuals. The remaining RCTs
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evaluated enteral nutrition and standard oral supplements and demonstrated no
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benefit. However, most of the studies included in the meta-analyses (in particular
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the parenteral nutrition studies) are not relevant to current practice since most
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protocols for peri-operative management of surgical patients do not recommend
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these interventions any more.
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There is also a recently published Cochrane review that assessed the
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effectiveness of preoperative smoking interventions on smoking cessation at the time
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of surgery [20]. This identified seven RCTs that examined the effect of smoking
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cessation interventions (including pharmacotherapy such as nicotine replacement)
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on postoperative complications. Two of these RCTs involved intense interventions
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(face-to-face or telephone counselling) and five involved brief interventions (e.g.one
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counselling session before surgery and additional telephone support during normal
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working hours if patients needed it). There was significant heterogeneity between
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intensive and brief interventions so data were analysed for these subgroups
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separately. Results suggested a significant effect of intensive smoking cessation
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intervention (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.27 to 0.65) but not
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brief intervention (RR 0.92, 95% CI, 0.72 to 1.19) on risk of any postoperative
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complication.
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Recent studies have included other components in their prehabilitation
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programmes. In a pilot non randomised study in patients undergoing elective
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surgery for primary colorectal cancer, Li et al showed that a one month
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prehabilitation programme including nutritional counselling, protein supplementation,
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and anxiety reduction techniques in addition to a moderate exercise program
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increased postoperative walking capacity (at 4 and 8 weeks after surgery) and health
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related quality of life, and improved recovery time after surgery [12].
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We intend to carry out a systematic review to identify all RCTs assessing
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interventions that have been used to try to improve postoperative outcomes in
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patients undergoing elective surgery. This review needs to be conducted for the
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following reasons:
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1. There is evidence that interventions other than physical activity improve
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postoperative outcomes in patients undergoing surgery; some of these have not
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been systematically identified and included in previous reviews.
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2. There is a need to update existing systematic reviews with recent randomised controlled trials (RCTs). 3. There is a need to assess the methodological quality of RCTs of all interventions administered before elective surgery.
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Objectives
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The objectives of this review are to: (a) identify different types of intervention (e.g.
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physical activity, nutritional, psychosocial, clinical) that have been used prior to
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surgery in patients undergoing elective surgery; (b) to evaluate the benefits and
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harms of these interventions; and (c) to compare the effectiveness of the different
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components.
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Methods
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Criteria for considering studies for this review
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Types of studies
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All published and unpublished randomised controlled trials (RCTs) will be included.
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Observational study designs were considered for inclusion, as they have been
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included in three previous systematic reviews of physical activity interventions.
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Observational studies were not included for the following reasons: sufficient RCTs
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are known to be available for different types of intervention (e.g. physical activity,
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nutritional, smoking cessation, multicomponent), all of which include the outcomes of
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interest; and observational studies are likely to be at higher risk of bias and
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confounding by indication, because interventions may be administered to certain
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subgroups of patients based on their risk of postoperative morbidity
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Types of participants
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Studies on adult patients (18 years and older) undergoing elective surgery (curative
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or palliative), not including day case surgery will be included. We decided not to
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restrict the population to specific subgroups of surgery patients (e.g. cancer)
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because there are a limited number of RCTs available overall and we want to
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characterise all of these to determine whether they are transferrable or subgroup
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specific.
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Types of interventions
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All studies that have assessed the effectiveness of any intervention administered
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before elective surgery aimed at improving short term (up to 3 months) postoperative
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outcomes compared with no intervention (or usual care) will be included. These
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could include (but are not restricted to) the following types of interventions:
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a) Physical activity (e.g. strength training, aerobic, specific exercises relating to the area being operated on). b) Nutritional (e.g. diet plans for weight loss or optimising nutrition for malnourished
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patients, oral supplementation, including macro- and micronutrients and
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immunonutrition). We will not include studies involving the administration of
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enteral and parenteral nutrition.
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c) Educational (e.g. advice, guidance, education, self-care strategies).
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d) Psychological (e.g. anxiety reducing, any cognitive or behavioural intervention,
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or combined cognitive behavioural intervention). e) Clinical (e.g. optimising medication, diabetes/blood glucose control, treating anaemia, interventions designed to obtain a good ‘baseline’ status).
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f) Smoking, alcohol, drug cessation/reduction interventions.
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g) Multicomponent (e.g. including one or more of the above).
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This list is not exhaustive, and any other interventions administered
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preoperatively to improve postoperative outcomes identified through the literature
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searches will be included. We will not impose a time limit on the length of these
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interventions, but any intervention administered less than 24 hours before surgery, or
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after the patient has been admitted to hospital will be excluded. We will also exclude
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studies in which the interventions was continued postoperatively. Studies in which
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the intervention was part of an ERAS programme will be also be excluded.
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Justification for the inclusion of multiple interventions in the review
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It can be argued that the proposed systematic review is ambitious given the large
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number of potential interventions, each of which could constitute a separate review.
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However, an initial scoping of the literature did not identify a large number of RCTs
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for the different interventions. Physical activity, nutritional and smoking cessation
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interventions were most commonly identified and there are existing systematic
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reviews of these interventions. We will avoid unnecessary duplication of research
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effort and use the conclusions of any relevant high quality systematic review. Quality
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of each review will be assessed using the ROBIS criteria [21] and if the review meets
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quality criteria, we will contact the study authors and update the meta analysis of the
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review with any new studies identified. For systematic reviews that do not meet the
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quality criteria, we will assess risk of bias and extract data from all the RCTs
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identified.
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Text mining to identify additional relevant interventions
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A search based on the above components may miss important interventions that
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have the potential to influence surgical outcome. A standard approach was used to
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develop the search strategy, including reading of background literature and relevant
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papers, examining the search syntax of similar systematic reviews and using clinical
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knowledge of relevant terms. However, because the topic is broad and
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multidisciplinary and may be inconsistently referred to in the literature, there is a risk
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that important evidence that uses different terminology will be missed. Therefore, if
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time and resources permit, text mining will be used alongside standard search term
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development methods to identify relevant search terms. Relevant full text papers
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and reviews identified through our traditional search will be run through a term
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extraction programme such as TerMine to identify additional key terms and
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compound terms, which will be added to the existing search strategies.
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Types of outcome measures
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Primary outcomes
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Postoperative complications: infective (e.g. chest infections, pneumonia,
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wound infections); non-infective (e.g. anastomotic leak, wound dehiscence,
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organ failure or thromboembolism)
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Length of hospital stay
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All cause perioperative mortality (30d)
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Secondary outcomes
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Length of stay in intensive care unit (ICU) and/or high dependency unit (HDU)
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Perioperative morbidity (acute coronary event, stroke)
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Hospital readmission
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Postoperative pain
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Health related quality of life (HRQoL)
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Outcomes specific to intervention: physical activity (e.g. forced expiratory
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volume in 1 second (FEV1); cardiopulmonary exercise testing (CPET); muscle
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function tests such as 6 minute walk tests, muscle strength and motor
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function, inspiratory muscle function); nutritional (e.g. body weight, body 11
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composition, body mass index, biochemical markers such as serum albumin);
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psychological (e.g. anxiety, distress, depression, fatigue); clinical (e.g. mean
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blood glucose during intervention); alcohol/drug cessation (reported
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abstinence/reduction, biochemical validation)
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Any reported adverse effects
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Resource use
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Search methods for identification of studies
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The following electronic databases were used to identify relevant trials. Searches
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were not restricted by language or publication status. Searches were conducted on
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9 March 2015.
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1. MEDLINE and PreMEDLINE (OvidSP) (1950 to date)
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2. EMBASE Classic + EMBASE (OvidSP) (1974 to date)
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3. CENTRAL, DARE, HTA and NHS EED (The Cochrane Library, latest Issue)
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4. CINAHL (1981 to date)
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5. PsychINFO (1806 to date)
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6. ISI Web of Science: Science Citation Index Expanded (SCIEXPANDED)
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(1900 to date) 7. ISI Web of Science: Conference Proceedings Citation Index-Science (CPCIS) (1990 to date).
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We considered whether to search Complementary and Alternative Medicines (CAM)
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databases to identify CAM interventions (e.g. homeopathy; acupuncture, osteopathy,
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yoga, herbalism, etc.) that have been used in patients before surgery to improve
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outcomes, but decided not to do so for the following reasons: (a) the methodological
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and reporting quality of CAM trials is generally poor [22, 23] so it is unlikely that
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conclusions could be drawn from these studies and that any CAM interventions
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could be incorporated into a prehabilitation intervention; (b) there is a growing body
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of evidence that questions the effectiveness of CAM therapies and their underlying
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theories [24]; (c) there are limited resources and time available to complete this
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review.
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Searching other resources
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All the reference lists of all included studies and published systematic reviews will be
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hand searched. Databases of ongoing trials will also be searched: Current
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Controlled Trials (www.controlled-trials.com with links to other databases of ongoing
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trials) and the WHO International Clinical Trials Registry Platform
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(www.who.int/ictrp/en/). Grey literature databases (e.g. OpenGrey), the Google
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search engine and a combination of key text words to identify studies published in
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non-indexed journals, theses and dissertations, and published POA protocols will
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also be used. Experts in the field and trial authors will be contacted for further
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information or unpublished data. The search strategy for Medline is shown in
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Appendix 1. This was adapted as appropriate for searching the other databases.
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Data collection and analysis
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Selection of studies
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Two review authors will independently screen titles and abstracts to determine
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eligibility. Full text papers will be obtained for all studies deemed eligible or studies
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that do not provide sufficient information to exclude at the screening stage. All full
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text papers will be assessed for eligibility by two review authors independently;
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studies not meeting the inclusion criteria will be excluded and the reasons for
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exclusion will be recorded. Disagreements will be resolved by discussion and
325
consensus with a third review author. The study selection process will be presented
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in a PRISMA flow diagram.
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Data extraction and management
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The following information will be extracted from each study:
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1. Publication details (authors, title, date of publication, country of origin, funding source, corresponding author contact details). 2. Study characteristics (setting, study design, method of randomisation
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(sequence generation, concealment of allocation), blinding of outcome
334
assessors, number of patients randomised to each group).
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3. Participant characteristics (demographics, inclusion and exclusion criteria,
336
clinical characteristics (e.g. type and extent of disease, presence of co-
337
morbidities, proportion of malnourished patients (defined by body mass index
338
25 kg/m2 or >30kg/m2, respectively), subjective global
340
assessment or nutrition risk derived from a validated tool, functional capacity
341
parameters).
342 343
4. Surgery characteristics (e.g. type of surgery, perioperative management (e.g. ERAS or traditional).
344
5. Intervention and comparator characteristics. These will be pre-specified for
345
each type of intervention. We will also extract information from all included
346
studies on the following factors: mode of delivery (verbal, written, computer,
347
phone app); place of delivery (hospital, home, other); who delivered the
348
intervention (doctor, nurse, other health professional); training for individuals
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delivering the intervention (yes/no); duration of intervention; number of
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sessions; format (individual or group); level of commitment required from
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patient (high/medium/low); acceptability of the intervention to patient. We will
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extract information on compliance with the intervention.
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6. Outcomes (as detailed in previous section). We will record the number of
354
participants assessed for each outcome, mean values and standard
355
deviations (if available) or medians and interquartile ranges for continuous
356
data, number of events in each group for categorical data, and any reported
357
summary statistics (e.g. effect estimates, confidence intervals (CI), standard
358
errors (SE), ranges). We will contact the trial authors for information if any of
359
the above data items are missing.
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Dealing with duplicate publications
362
Where multiple papers have reported the same study but different outcomes, all will
363
be used to extract the relevant outcome data.
364 365
Assessment of risk of bias in included studies
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Risk of bias for each included study will be assessed independently by at least two of
367
the three review authors. We will use The Cochrane Collaboration’s tool [25] for
368
assessing risk of bias and rate the quality of each trial (low risk, unclear and high
369
risk) in the following areas: generation of allocation sequence (selection bias);
370
allocation concealment (selection bias); blinding of participants, personnel and
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outcome assessors (performance bias and detection bias); incomplete outcome data
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(attrition bias); selective reporting (reporting bias); other sources (e.g. presentation
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data bias, sampling bias, sponsorship bias).
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Blinding of participants and health care professionals in trials involving
375
physical activity interventions, dietary changes (unless it involves oral
376
supplementation), educational and psychological interventions, and
377
smoking/alcohol/drug cessation/reduction interventions is likely to be difficult and
378
complete blinding may not be possible. To account for outcome-specific variation in
379
performance bias, detection bias and selective outcome reporting bias, risk of bias
380
will be assessed separately for the following pre-specified outcome domains:
381
perioperative mortality; hospital readmission; postoperative complications and
382
morbidity, length of stay (ITU/HDU/hospital); patient reported outcomes
383
(postoperative pain, HRQoL, psychological outcomes); clinical measurements (e.g.
384
cardiopulmonary testing parameters, muscle function tests, BMI, biomarkers).
385
Different criteria will be used to assess risk of bias for each domain, so for example,
386
lack of blinding of outcome assessors is less likely to influence outcomes such as
387
mortality and hospital readmission, so these outcomes will be judged to be at low
388
risk of performance and detection bias; whereas lack of any attempt to blind
389
participants is likely to influence patient reported outcomes, so these outcomes will
390
be judged to be at high risk of detection bias. Similarly, clinical measurement
391
outcomes will be judged to be at low risk of detection bias if outcome assessors are
392
blinded, regardless of whether or not patients and personnel are blinded.
393 394
Assessment of adverse events in included studies
395
An assessment of the effectiveness of an intervention requires evidence of both
396
benefits and harms. Although RCTs may be poor at identifying and reporting harms
397
of an intervention [26, 27], any additional information about adverse events that may
398
be related to the intervention and assess the risk of bias as for the other outcomes
16
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
399
will be extracted. In addition, patient risk factors and length of follow-up when
400
reviewing adverse events will also be considered, as will the risk of reporting bias for
401
adverse events.
402 403
Measures of treatment of effect
404
For dichotomous outcomes (mortality, morbidity, hospital readmission, adverse
405
events and most postoperative complications) we will calculate pooled risk ratios
406
(RRs) and 95% confidence intervals (CIs). For continuous outcomes (most patient
407
reported outcomes, physiological and clinical parameters), we will calculate pooled
408
mean differences and 95% confidence intervals (CIs) when results are reported on
409
the same scale (or can be converted to the same scale), or standardised mean
410
differences and 95% CI if results are reported on different scales. Length of
411
ITU/HDU/hospital stay, although strictly speaking time-to-event data, are often
412
reported as continuous data despite the fact that such data are unlikely to be
413
normally distributed. However, if authors report medians and interquartile ranges
414
(allowing for censoring), we will calculate hazard ratios (HR) and 95% CIs. If no
415
appropriate data are available, then length of stay will be reported narratively.
416 417
Unit of analysis issues
418
We will take into account multiple observations for the same outcome and the level
419
at which randomisation occurred, although we are not aware of any cluster
420
randomised trials.
421 422
Dealing with missing data
17
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
423
If data required are not available in the publication, we will first attempt to back-
424
calculate from data presented (e.g. numerator or denominator from percentages;
425
standard deviation from standard errors or 95% CIs). If this is not possible we will
426
attempt to contact the study authors. We are aware that studies assessing lifestyle
427
interventions may have issues with compliance, therefore we will carefully report
428
reasons for missing data (e.g. drop-outs, losses to follow-up and withdrawals).
429 430
Assessment of heterogeneity
431
We will assess clinical heterogeneity across studies by examining variability in the
432
details of participants, baseline data, interventions, and outcomes to determine
433
whether studies are similar. Statistical heterogeneity will be quantified using the I2
434
statistic; we will consider the statistical heterogeneity to be high if I2 > 50% [25].
435
We will attempt to explain any observed clinical or statistical heterogeneity in the
436
results of the review.
437 438
Reporting biases
439
Funnel plots will be used to assess publication bias when 10 or more studies are
440
included in a meta-analysis.
441 442
Data synthesis
443
We will attempt to combine the results for trials that use similar interventions (e.g.
444
physical activity, nutritional, educational, psychological, clinical, etc.) and report
445
similar outcomes. However, even with similar interventions there is likely to be
446
substantial heterogeneity in the types of participants, the intervention and its
447
delivery. We will therefore be using random effects meta-analysis models for our
18
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
448
primary analysis to pool data across trials, although fixed-effects meta-analysis
449
models will also be explored. The findings from the included studies will be
450
summarised in narrative form if we do not find trials that are sufficiently similar to
451
justify a meta-analysis.
452 453
Subgroup analyses and investigation of heterogeneity
454
If data from sufficient trials are available, we will attempt to perform subgroup
455
analyses for the following subgroups:
456
1. Type of surgery (e.g. orthopaedic, cardiac, cancer).
457
2. Type of intervention (e.g. intensive or brief).
458
3. Intervention conducted in the context of an ERAS programme vs no ERAS
459 460
programme. 4. High vs low risk surgical patients.
461 462
Sensitivity analyses
463
We will conduct sensitivity analyses to include only trials classified as having good
464
allocation concealment. Sensitivity analysis excluding trials with more than 20%
465
drop out rate will be performed to assess the impact of missing data on our results
466
and conclusions. The impact of removing any study that has a large effect size from
467
the meta-analyses will also be assessed.
468 469
Authors’ contributions
470
MP: conception, design and manuscript writing. RP: conception and design. LS and
471
JH: statistical advice, critical revision of the manuscript. AR: design of search
472
strategies. ARN: methodological advice and critical revision of the manuscript. CA:
19
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
473
critical revision of the manuscript. LC: critical revision of the manuscript. AH: critical
474
revision of the manuscript. JS: methodological advice on systematic review. SS:
475
clinical advice and critical revision of clinical content. All authors have read and
476
approved the final manuscript.
477 478
Funding
479
This study is part of a project funded by the Elizabeth Blackwell Institute Research
480
for Health Challenge, University of Bristol.
481 482
Competing interests
483
The authors declare that they have no competing interests.
484 485
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22
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586
Appendix 1
587
Search strategy
588
Database: Medline In-process - Current week, Medline 1950 to present
589
Search Strategy:
590
--------------------------------------------------------------------------------
591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630
1 (pre-hab$ or prehab$).ti,ab. (119) 2 ((presurg$ or preoperativ$ or pre-surg$ or pre-operativ$) adj3 (conditioning or optimis$ or optimiz$ or rehab$ or re-hab$ or care)).ti,ab. (1790) 3 (pre adj2 (postsurg$ or postoperativ$) adj3 (conditioning or optimis$ or optimiz$ or rehab$ or re-hab$ or care)).ti,ab. (406) 4 ((before or prior to) adj3 (CABG or surgery or surgical or procedure$ or arthroplast$ or hip replacement or knee replacement or joint replacement or total hip or total knee or total joint$ or operation) adj12 (conditioning or optimis$ or optimiz$ or rehab$ or re-hab$ or care)).ti,ab. (1137) 5 Preoperative Care/mt, rh [Methods, Rehabilitation] (9939) 6 (preoperative care/ or preoperative period/) and (conditioning or optimis$ or optimiz$ or rehab$ or re-hab$).ti,ab. (1435) 7 Postoperative Complications/pc and ((presurg$ or preoperativ$ or pre-surg$ or pre-operativ$) adj3 (assess$ or intervention$)).ti,ab. (349) 8 or/1-7 (14185) 9 preoperative care/ or preoperative period/ (54529) 10 (presurg$ or preoperativ$ or pre-surg$ or pre-operativ$).ti,ab. (224877) 11 (pre adj2 (postsurg$ or postoperativ$)).ti,ab. (12194) 12 ((before or prior to) adj3 (CABG or surgery or surgical or procedure$ or hip replacement or knee replacement or joint replacement or total hip or total knee or total joint$ or arthroplast$ or operation)).ti,ab. (83657) 13 or/9-12 (316706) 14 exp Exercise/ or exp Exercise Therapy/ (146992) 15 physical therapy modalities/ (28521) 16 physical fitness/ (22302) 17 (exercis$ or aerobic$ or swim$ or hydrotherapy or preconditioning or preconditioning or physical fitness or physical activit$ or physiotherap$ or physical therap$).ti,ab. (365238) 18 ((muscle or endurance or resistance or weight or strength) adj2 training).ti,ab. (13555) 19 ((function or functional capacity) adj2 (enhanc$ or improv$ or maximis$)).ti,ab. (39597) 20 Nutrition Therapy/ or exp diet therapy/ or exp diet/ or eating/ or nutritional physiological phenomena/ or elder nutritional physiological phenomena/ or nutritional requirements/ or nutritional status/ (288993) 21 exp Dietary Supplements/ or exp Food, Fortified/ (50721) 22 exp Malnutrition/dh, pc, rh, th [Diet Therapy, Prevention & Control, Rehabilitation, Therapy] (12552) 23 (diet$ or nutrition$ or malnutrition or underweight or low BMI or undernourish$ or undernutrition or malnourish$ or immunonutrition or macronutrient$ or 23
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680
micronutrient$ or immuno-nutrition or macro-nutrient$ or micro-nutrient$).ti,ab. (568387) 24 ((oral or food or multinutrient$ or multi-nutrient$ or multivitamin$ or iron or protein or folate or vitamin$) adj3 supplement$).ti,ab. (33003) 25 ((iron or protein or folate or vitamin$) adj3 (deficient or deficiency)).ti,ab. (47403) 26 ((fortif$ or enrich$) adj3 (food$ or feed$)).ti,ab. (3276) 27 (weight adj2 (loss or lose$ or lost or losing) adj2 (program$ or plan$)).ti,ab. (1818) 28 (fortisip or complan).ti,ab. (17) 29 Adaptation, Psychological/ (76095) 30 Cognitive Therapy/ or Psychotherapy/ or exp Mind-body therapies/ or behavior therapy/ or mindfulness/ (116265) 31 ((counselling or counseling) adj2 (session$ or therap$ or intervention$)).ti,ab. (3428) 32 mindfulness.ti,ab. (2121) 33 (CBT or ((cognitive or talking or mental health or behavio?ral) adj3 (intervention$ or therap$))).ti,ab. (27170) 34 ((education$ or psychoeducational or psychotherapeutic or psychological or psychosocial or behavio?ral or cognitive) adj3 (intervention$ or program$)).ti,ab. (67734) 35 ((anxiety or stress or fear) adj2 (manag$ or strateg$ or therap$ or reduc$)).ti,ab. (24159) 36 ((selfcare or self-care or self-help or coping) adj2 (mechanism$ or strateg$ or behavio?r$)).ti,ab. (13440) 37 Smoking Cessation/ (20803) 38 ((smoking or drug$) adj2 (cessation or stop$ or quit$ or giving up or give up)).ti,ab. (24592) 39 (nicotine replacement therapy or NRT).ti,ab. (2339) 40 (alcohol adj2 reduc$).ti,ab. (4053) 41 Blood Glucose Self-Monitoring/ (4398) 42 ((blood sugar or blood glucose or diabetes) adj2 (level or levels or control$ or monitor$)).ti,ab. (32523) 43 Anemia/dt, pc, th [Drug Therapy, Prevention & Control, Therapy] (10586) 44 ((an?emia or an?emic) adj3 (iron or prevent$ or treat$ or control$)).ti,ab. (16266) 45 ((blood pressure or BP or hypertens$) adj2 (control$ or manag$ or medication$)).ti,ab. (28359) 46 ((COPD or angina) adj2 (control$ or manag$ or medication$)).ti,ab. (2158) 47 Geriatric Assessment/ (19045) 48 ((geriatric or baseline status) adj2 assessment$).ti,ab. (2248) 49 ((optimiz$ or optimis$) adj2 medication$).ti,ab. (251) 50 (pre-existing adj2 (comorbidit$ or co-morbidit$ or chronic illness$ or chronic disease$ or chronic condition$)).ti,ab. (233) 51 or/14-50 (1543244) 52 8 or (13 and 51) (32833) 53 letter/ (867912) 54 editorial/ (371347) 55 news/ (167087) 56 exp historical article/ (328799) 24
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726
57 Anecdotes as topic/ (4603) 58 comment/ (615244) 59 case report/ (1715831) 60 (letter or comment$).ti. (101137) 61 or/53-60 (3438065) 62 randomized controlled trial/ or Randomized Controlled Trials as Topic/ or random$.ti,ab. (896854) 63 61 not 62 (3406560) 64 animals/ not humans/ (3906384) 65 exp Animals, Laboratory/ (735772) 66 exp Animal Experimentation/ (6519) 67 exp Models, Animal/ (428521) 68 exp rodentia/ (2704363) 69 (rat or rats or mouse or mice or animal or animals).ti. (1219737) 70 or/63-69 (7953941) 71 52 not 70 (28469) 72 (exp child/ or exp infant/) not adult/ (1398640) 73 ((child$ or infant$ or newborn$ or neonat$) not adult$).ti. (826483) 74 72 or 73 (1610061) 75 71 not 74 (26156) 76 meta-analysis/ (53771) 77 meta-analysis as topic/ (14025) 78 (meta analy$ or metaanaly$ or metanaly$ or meta regression).ti,ab. (73844) 79 ((systematic$ or evidence$) adj2 (review$ or overview$)).ti,ab. or review.ti. (315502) 80 (reference list$ or bibliograph$ or hand search$ or manual search$ or relevant journals).ab. (27398) 81 (search strategy or search criteria or systematic search or study selection or data extraction).ab. (29241) 82 (search$ adj4 literature).ab. (31134) 83 (medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or cinahl or science citation index or bids or cancerlit).ab. (96758) 84 cochrane.jw. (11169) 85 ((multiple treatment$ or indirect or mixed) adj2 comparison).ti,ab. (1006) 86 or/76-85 (435094) 87 randomized controlled trial.pt. or randomized controlled trial/ or Randomized Controlled Trials as Topic/ (477876) 88 controlled clinical trial.pt. (88869) 89 ((doubl$ or singl$ or trebl$ or tripl$) adj blind$).ti,ab. (130373) 90 random$.ti,ab. (749676) 91 clinical trials as topic.sh. (171370) 92 trial.ti. (134197) 93 (controlled adj clinical trial).ti,ab. (9292) 94 or/87-93 (1143831) 95 75 and (86 or 94) (4843)
25
