Perioperative medicine training resources: U3M9: Complex morbidities and options for optimisation

Abstract
Background: Patients with diabetes mellitus are at increased risk of postoperative complications. Data from randomised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control, targeting near-normal blood glucose, in patients with hyperglycaemia (with and without diabetes mellitus) being submitted to surgical procedures. However, there is limited evidence concerning this question in patients with diabetes mellitus undergoing surgery.

Objectives: To assess the effects of perioperative glycaemic control for diabetic patients undergoing surgery.

Search methods: Trials were obtained from searches of The Cochrane Library, MEDLINE, EMBASE, LILACS, CINAHL and ISIS (all up to February 2012).

Selection criteria: We included randomised controlled clinical trials that prespecified different targets of perioperative glycaemic control (intensive versus conventional or standard care)

Data collection and analysis: Two authors independently extracted data and assessed risk of bias. We summarised studies using meta-analysis or descriptive methods.

Main results: Twelve trials randomised 694 diabetic participants to intensive control and 709 diabetic participants to conventional glycaemic control. The duration of the intervention ranged from just the duration of the surgical procedure up to 90 days. The number of participants ranged from 13 to 421, and the mean age was 64 years. Comparison of intensive with conventional glycaemic control demonstrated the following results for our predefined primary outcomes: analysis restricted to studies with low or unclear detection or attrition bias for infectious complications showed a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.18 to 1.18), P = 0.11, 627 participants, eight trials, moderate quality of the evidence (grading of recommendations assessment, development and evaluation - (GRADE)). Evaluation of death from any cause revealed a RR of 1.19 (95% CI 0.89 to 1.59), P = 0.24, 1365 participants, 11 trials, high quality of the evidence (GRADE).On the basis of a posthoc analysis, there is the hypothesis that intensive glycaemic control may increase the risk of hypoglycaemic episodes if longer-term outcome measures are analysed (RR 6.92, 95% CI 2.04 to 23.41), P = 0.002, 724 patients, three trials, low quality of the evidence (GRADE). Analysis of our predefined secondary outcomes revealed the following findings: cardiovascular events had a RR of 1.03 (95% CI 0.21 to 5.13), P = 0.97, 682 participants, six trials, moderate quality of the evidence (GRADE) when comparing the two treatment modalities; and renal failure also did not show significant differences between intensive and regular glucose control (RR 0.61, 95% CI 0.34 to 1.08), P = 0.09, 434 participants, two trials, moderate quality of the evidence (GRADE). We did not meta-analyse length of hospital stay and intensive care unit (ICU) stay due to substantial unexplained heterogeneity. Mean differences between intensive and regular glucose control groups ranged from -1.7 days to 2.1 days for ICU stay and between -8 days to 3.7 days for hospital stay (moderate quality of the evidence (GRADE)). One trial assessed health-related quality of life in 12/37 (32.4%) of participants in the intervention group and 13/44 (29.5%) of participants in the control group, and did not show an important difference (low quality of the evidence (GRADE)) in the measured physical health composite score of the short-form 12-item health survey (SF-12). None of the trials examined the effects of the interventions in terms of costs.

Authors' conclusions: The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus. However, posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes. Intensive glycaemic control protocols with near-normal blood glucose targets for patients with diabetes mellitus undergoing surgical procedures are currently not supported by an adequate scientific basis. We suggest that insulin treatment regimens, patient- and health-system relevant outcomes, and time points for outcome measures should be defined in a thorough and uniform way in future studies.

Abstract
Purpose of Review
The purpose of this article is to provide a brief review of the preoperative pulmonary evaluation of patients undergoing non-thoracic surgery, focusing on risk factor identification, assessment of specific high-risk populations, and strategies to minimize postoperative pulmonary complications (PPCs).

Recent Findings
Along with traditional risk factors, recent risk stratification indices have been developed and validated to help quantify risk of PPCs. Careful history and physical examination are key elements in the pulmonary evaluation of all pre-surgical patients. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk and require more intensive optimization and perioperative monitoring. Well-controlled asthma has not been associated with increased risk of PPCs but the potential for life-threatening bronchospasm and status asthmaticus cannot be ignored. In general, the literature does not support delaying surgery for preoperative diagnosis and management of obstructive sleep apnea (OSA). Exceptions to this rule are patients presenting with evidence of obesity-hypoventilation syndrome or pulmonary hypertension. Recent literature provides more evidence of benefits of regional anesthesia and analgesia to decrease the risk of pulmonary complications, particularly in COPD patients.

Summary
PPCs are major contributors to perioperative morbidity and mortality. A thorough preoperative evaluation must identify high-risk patients, optimize chronic and acute respiratory diseases, and establish a clear perioperative plan to minimize PPCs.

Abstract
Background: Patients undergoing noncardiac, nonvascular surgery (NCNVS) are at risk of perioperative cardiovascular events. However, benefits of cardiology consultation (CC) in patients with known or suspected cardiac disease undergoing intermediate-risk NCNVS is unknown.

Methods: The study group included 700 consecutive patients referred for CC before intermediate-risk NCNVS in a tertiary-care teaching hospital. The control group included 1200 age-matched and sex-matched consecutive patients proceeded to the intermediate-risk surgery without preoperative CC during the same period. Patients older than 18 years who underwent an elective, NCNVS were enrolled. Requests for consultation were made either by surgeon or an attending anaesthesiologist. All patients underwent a complete preoperative clinical evaluation.

Results: Of the 700 patients who were referred for CC in the study group, 530 patients (75.7%) had no additional recommendations, and 170 patients (24.3%) underwent additional preoperative tests or had a change in preoperative therapy. Only 20 (2.8%) patients' NCNVS were delayed based on the cardiologists' recommendation and 680 patients eventually had their surgeries. Major cardiovascular and noncardiovascular complication rates were similar in the study and in the control groups (12.9% vs 13.6%, P = 0.273 and 25.2% vs 26%, P = 0.432 respectively).

Conclusions: Preoperative CC in patients who underwent intermediate-risk NCNVS does not affect either perioperative management or outcome of surgery.

Abstract
Background: Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures.Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery.This review was first published in 2012 and was updated in 2018.

Objectives: To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption.

Search methods: We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information.

Selection criteria: We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention.We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies.

Data collection and analysis: We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach.

Main results: We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study.Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate.In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low.Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate.All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term.

Authors' conclusions: This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term.Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.

Abstract
Background: Preoperative anemia is a common comorbidity that often necessitates allogeneic blood transfusion (ABT). As there is a risk associated with blood transfusions, preoperative intravenous iron (IV) has been proposed to increase the hemoglobin to reduce perioperative transfusion; however, randomized controlled trials (RCT) investigating this efficacy for IV iron are small, limited, and inconclusive. Consequently, a meta-analysis that pools these studies may provide new and clinically useful information.

Methods/design: Databases of MEDLINE, EMBASE, EBM Reviews; Cochrane-controlled trial registry; Scopus; registries of health technology assessment and clinical trials; Web of Science; ProQuest Dissertations and Theses; Clinicaltrials.gov; and Conference Proceedings Citation Index-Science (CPCI-S) were searched. Also, we screened all the retrieved reference lists.

Selection criteria: Titles and abstracts were screened for relevance (i.e., relevant, irrelevant, or potentially relevant). Then, we screened full texts of those citations identified as potentially applicable.

Results: Our search found 3195 citations and ten RCTs (1039 participants) that met our inclusion criteria. Preoperative IV iron supplementation significantly decreases ABT by 16% (risk ratio (RR): 0.84, 95% confidence interval [CI]: 0.71, 0.99, p = 0.04). In addition, preoperatively, hemoglobin levels increased after receiving IV iron (mean difference [MD] between the study groups: 7.15 g/L, 95% CI: 2.26, 12.04 g/L, p = 0.004) and at follow-up > 4 weeks postoperatively (MD: 6.46 g/L, 95% CI: 3.10, 9.81, p = 0.0002). Iron injection was not associated with increased incidence of non-serious or serious adverse effects across groups (RR: 1.13, 95% CI: 0.78, 1.65, p = 0.52) and (RR: 0.96, 95% CI: 0.44, 2.10, p = 0.92) respectively.

Conclusions: With moderate certainty, due to the high risk of bias in some studies in one or two domains, we found intravenous iron supplementation is associated with a significant decrease in the blood transfusions rate, and modest hemoglobin concentrations rise when injected pre-surgery compared with placebo or oral iron supplementation. However, further full-scale randomized controlled trials with robust methodology are required. In particular, the safety, quality of life, and cost-effectiveness of different intravenous iron preparations require further evaluation.

Abstract
People with diabetes mellitus (DM) undergo more elective surgery than those without DM; however, up to half of the patients are undiagnosed when referred for surgery. This is an opportunity to intervene and instigate a management plan. Preoperative strategies may vary based on coexisting medical diseases such as obesity and the availability of resources with the aim of achieving glycaemic control while also treating coexisting conditions. In the context of obesity, there is substantial overlap in some of the treatment strategies. Guidelines, such as those from the UK Centre for Perioperative Medicine, suggest target glycated haemoglobin levels, preoperative fasting blood glucose levels, and when to defer an elective operation or instigate treatment to proceed if deemed safe. Preoperatively glycaemic control is often achieved pharmacologically, and newer agents, including glucagon-like peptide one receptor agonists (GLP1-RA) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, are emphasised in the preoperative management of diabetes mellitus, particularly if obesity is also present. A very low-energy diet is an underutilised but well-evidenced method of achieving both glycaemic control and weight loss with a particularly dominant effect on liver fat which is helpful for people who are due to undergo abdominal surgery. Bariatric-metabolic procedures are of growing interest as bridging interventions to surgery and are more commonly used for obesity, but they also have a well-recognized impact on the improvement and remission of DM. This review gives an overview of the necessity of preoperative identification of DM and strategies for management. Intra-operative glycaemic control is also discussed, and the role of stress hyperglycaemia perioperatively.

Full citation:
Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(24):e278-e333.

Abstract
Objective: Obesity is responsible for a huge burden of suffering and social costs, and yet many patients lack access to evidence-based therapies. The diagnostic term "obesity" and inadequate International Classification of Diseases(ICD) codes contribute to suboptimal efforts to prevent and treat obesity as a chronic disease. The goal of this review is to develop a medically actionable classification system based on the diagnostic term "adiposity-based chronic disease" (ABCD) that reflects disease pathophysiology and specific complications causing morbidity and mortality.

Methods: A coding system based on the diagnosis of ABCD with four domains is proposed: A codes reflect pathophysiology, B codes indicate BMI classification, C codes specify specific biomechanical and cardiovascular complications remediable by weight loss, and D codes indicate the degree of the severity of complications. Supplemental codes identify aggravating factors that complicate care and that are relevant to a personalized therapeutic plan.

Results: The coding system addresses pathophysiology and therapeutic goals and differential risk, presence, and severity of specific complications that are integral to ABCD as a chronic disease.

Conclusions: The scientifically correct and medically actionable approach to diagnosis and disease coding will lead to greater acknowledgement of ABCD as a disease and accessibility to evidence-based therapies on behalf of patients across the life cycle.

Abstract
Purpose of review: Patients with cancer who have high levels of psychological distress have poor treatment compliance and worse outcomes. This "review of reviews" provides a narrative synthesis of the impact of psychological prehabilitation interventions on individuals awaiting cancer surgery.

Recent findings: Twenty reviews of prehabilitation with psychological interventions were identified. There is a trend towards improved psychological outcomes following intervention, particularly when psychologist-led. However, there was considerable heterogeneity within interventions, outcome measures, and timing of assessment precluding numeric synthesis. Methodological limitations including non-blinding, absence of stratification, and underpowered studies were also pervasive.

Summary: Providing psychological support early in the cancer pathway and prior to surgery has the potential to improve psychological health and outcomes. The application of existing knowledge in psycho-oncology, including distress screening, is needed in the prehabilitation setting. Consistent outcome assessments, accurate reporting of intervention components and delivery methods, and a consideration of effective systems and economical implementation strategies would facilitate advancements in this field.

Supplementary information: The online version contains supplementary material available at 10.1007/s40140-021-00505-x.

Abstract
Background: The cardiologist is regularly consulted preoperatively by anaesthesiologists. However, insights into the efficiency and usefulness of these consultations are unclear.

Methods: This is a retrospective study of 24,174 preoperatively screened patients ≥18 years scheduled for elective non-cardiac surgery, which resulted in 273 (1%) referrals to the cardiologist for further preoperative evaluation. Medical charts were reviewed for patient characteristics, main reason for referring, requested diagnostic tests, interventions, adjustment in medical therapy, 30-day mortality and major adverse cardiac events.

Results: The most common reason for consultation was the evaluation of a cardiac murmur (95 patients, 35%). In 167 (61%) patients, no change in therapy was initiated by the cardiologist. Six consultations (2%) led to invasive interventions (electrical cardioversion, percutaneous coronary intervention or coronary artery bypass surgery). On average, consultation delayed clearance for surgery by two weeks.

Conclusion: In most patients referred to the cardiologist after being screened at an outpatient anaesthesiology clinic, echocardiography is performed for ruling out specific conditions and to be sure that no further improvement can be made in the patient's health. In the majority, no change in therapy was initiated by the cardiologist. A more careful consideration about the potential benefits of consulting must be made for every patient.

Abstract
Objectives: to investigate the prevalence and impact of frailty for general surgical patients.

Research design and methods: we conducted a systematic review and meta-analysis. Studies published between 1 January 1980 and 31 August 2017 were searched from seven databases. Incidence of clinical outcomes (mortality at Days 30 and 90; readmission at Day 30, surgical complications and length of stay) were estimated by frailty subgroup (not-frail, pre-frail and frail).

Results: 2,281 participants from nine observational studies were included, 49.3% (1013/2055) were males. Mean age ranged from 61 to 77 years old. Eight studies provided outcome data and were quality assessed and of fair or good quality, and one study only provided an estimate of prevalence and was not quality assessed. The prevalence estimate ranged between 31.3 and 45.8% for pre-frailty, and 10.4 and 37.0% for frailty. After pooling, Day 30 mortality was 8% (95% CI: 4-12%; I2 = 0%) for frail compared to 1% for non-frail patients (95% CI: 0-2%; I2 = 75%). Due to heterogeneity the Day 90 mortality was not pooled. Readmission rates were lower in the non-frail groups but were not pooled. Complications for the frail patients were 24%, (95% CI: 20-31%; I2 = 92%), pre-frail subgroup 9% (95% CI: 5-14%; I2 = 82%) and non-frail 5% (95% CI: 3-7%; I2 = 70%). The mean length of stay in frail people was 9.6 days (95% CI: 6.2-12.9) and 6.4 days (4.9-7.9) non-frail.

Conclusions: frailty is associated with adverse post-operative outcomes in general surgery.

Abstract
Substance use disorders (SUDs) represent a current major public health concern in the United States and around the world. Social and economic stressors secondary to the coronavirus disease 2019 (COVID-19) pandemic have likely led to an increase in SUDs around the world. This chronic, debilitating disease is a prevalent health problem, and yet many clinicians do not have adequate training or clinical experience diagnosing and treating SUDs. Anesthesiologists and other perioperative medical staff frequently encounter patients with co-occurring SUDs. By such, through increased awareness and education, physicians and other health care providers have a unique opportunity to positively impact the lives and improve the perioperative outcomes of patients with SUDs. Understanding commonly used terms, potentially effective perioperative screening tools, diagnostic criteria, basics of treatment, and the perioperative implications of SUDs is essential to providing adequate care to patients experiencing this illness.

Abstract
Cardiac events remain the leading cause of peri-operative morbidity and mortality, and patients undergoing major surgery are exposed to significant risks which may be preventable and modifiable. Proper assessment and management of various cardiac conditions in the peri-operative period by anaesthetists can markedly improve patient safety, especially in high-risk patient populations. This involves understanding and applying current evidence-based practice and international guidelines on the main aspects of cardiac optimisation, including management of patients with hypertension, chronic heart failure, valvular heart diseases and cardiac implantable electronic devices. Peri-operative management of antihypertensive drugs in keeping with the current best evidence is discussed. Pre-operative cardiac risk assessment and cardiac biomarkers can be used to help predict and quantify peri-operative adverse cardiac events. There is an increasing need for anaesthetist-led services, including focused transthoracic echocardiography and management of implantable cardiac electronic devices. Anaesthetists should be encouraged to play a proactive role in pre-operative risk stratification and make timely multidisciplinary referrals if necessary. A personalised approach to pre-operative cardiac optimisation enables a safer peri-operative journey for at-risk patients undergoing major surgery.

Abstract
Background: Health-care worker (HCW) hand hygiene (HH) is the cornerstone of efforts to reduce hospital infections but remains low. Real-time mitigation of failures can increase process reliability to > 95% but has been challenging to implement for HH.

Objective: To sustainably improve HCW HH to > 95%.

Methods: A hospital-wide quality improvement initiative to improve HH was initiated in February 2012. HCW HH behavior was measured by covert direct observation utilizing multiple-trained HCW volunteers. HH compliance was defined as correct HH performed before and after contact with the patient or the patient's care area. Interventions focusing on leadership support, HCW knowledge, supply availability, and culture change were implemented using quality improvement science methodology. In February 2014, the hospital began the Speaking Up for Safety Program, which trained all HCWs to identify and mitigate HH failures at the moment of occurrence and addressed known barriers to speaking up.

Results: Between January 1, 2012, and January 31, 2016, there were 30,514 HH observations, averaging 627 observations per month (9% attending physicians, 12% resident physicians, 46% nurses, 33% other HCW types). HCW HH gradually increased from 75% to > 90% by December 2014. After the Speaking Up for Safety Program, HCW HH has been > 95% for 20 months. Physician HH compliance has been above 90% for over a year.

Conclusion: Creating a specific process for staff to speak up and prevent HH failures, as part of a multimodal improvement effort, can sustainably increase HCW HH above 95%.

Abstract
Importance: Enhanced Recovery After Surgery (ERAS) is a paradigm shift in perioperative care, resulting in substantial improvements in clinical outcomes and cost savings.

Observations: Enhanced Recovery After Surgery is a multimodal, multidisciplinary approach to the care of the surgical patient. Enhanced Recovery After Surgery process implementation involves a team consisting of surgeons, anesthetists, an ERAS coordinator (often a nurse or a physician assistant), and staff from units that care for the surgical patient. The care protocol is based on published evidence. The ERAS Society, an international nonprofit professional society that promotes, develops, and implements ERAS programs, publishes updated guidelines for many operations, such as evidence-based modern care changes from overnight fasting to carbohydrate drinks 2 hours before surgery, minimally invasive approaches instead of large incisions, management of fluids to seek balance rather than large volumes of intravenous fluids, avoidance of or early removal of drains and tubes, early mobilization, and serving of drinks and food the day of the operation. Enhanced Recovery After Surgery protocols have resulted in shorter length of hospital stay by 30% to 50% and similar reductions in complications, while readmissions and costs are reduced. The elements of the protocol reduce the stress of the operation to retain anabolic homeostasis. The ERAS Society conducts structured implementation programs that are currently in use in more than 20 countries. Local ERAS teams from hospitals are trained to implement ERAS processes. Audit of process compliance and patient outcomes are important features. Enhanced Recovery After Surgery started mainly with colorectal surgery but has been shown to improve outcomes in almost all major surgical specialties.

Conclusions and relevance: Enhanced Recovery After Surgery is an evidence-based care improvement process for surgical patients. Implementation of ERAS programs results in major improvements in clinical outcomes and cost, making ERAS an important example of value-based care applied to surgery.

Abstract
Background: We developed clinical practice guidelines to provide health care providers with evidence-based recommendations for decisions related to the effective management of frailty and pre-frailty using nutrition and physical activity interventions.

Methods: We based the recommendations on two systematic reviews with meta-analyses. Nutrition, physical activity, and combined nutrition and physical activity interventions for adults ≥65y were considered if study populations were identified as frail using a frailty tool or assessment. Risk of bias and certainty of evidence were evaluated. We included physical outcomes, mobility, frailty, cognitive function, activities of daily living, falls, quality of life, diet quality, energy/fatigue levels, health services use, and caregiver outcomes.

Results: Overall, mobility improvements were moderate with nutritional strategies that optimize dietary intake, various types of physical activity interventions, and interventions that combine nutrition and physical activity. Physical outcomes, such as body mass and muscle strength, improved moderately with nutritional strategies and interventions that combined nutrition with physical activity. Frailty status improved with multi-component physical activity interventions. Strong recommendations include optimizing dietary intake, performing physical activity, and adopting interventions that combine nutrition and physical activity. We strongly recommend various types of physical activity including muscle strengthening activities, mobilization or rehabilitation exercises, and multi-component physical activity interventions.

Interpretation: Tailored nutrition and physical activity interventions based on individual goals and health status are associated with improved clinical and physical outcomes. While the recommendations facilitate shared decision-making, we identified sparse application of validated frailty assessments and lack of standardized research outcomes as critical gaps in knowledge.

Abstract
Objective: To assess the association between having a serious mental illness and surgical outcomes for adults, including in-hospital and 30-day mortality, post-operative complications, and hospital length of stay.

Study design: Systematic review and meta-analysis of publications in English to 30 July 2018 of studies that examined associations between having a serious mental illness and surgical outcomes for adults who underwent elective surgery. Primary outcomes were in-hospital and 30-day mortality, post-operative complications, and length of hospital stay. Risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. Studies were grouped by serious mental illness diagnosis and outcome measures. Odds ratios (ORs) or mean differences (MDs), with 95% confidence intervals (CIs), were calculated in random effects models to provide pooled effect estimates.

Data sources: MEDLINE, EMBASE, PsychINFO, and the Cochrane Library.

Data synthesis: Of the 3824 publications identified by our search, 26 (including 6 129 806 unique patients) were included in our analysis. The associations between having any serious mental illness diagnosis and having any post-operative complication (ten studies, 125 624 patients; pooled effect: OR, 1.44; 95% CI, 1.15-1.79) and a longer stay in hospital (ten studies, 5 385 970 patients; MD, 2.6 days; 95% CI, 0.8-4.4 days) were statistically significant, but not those for in-hospital mortality (three studies, 42 926 patients; OR, 1.21; 95% CI, 0.69-2.12) or 30-day mortality (six studies, 83 013 patients; OR, 1.85; 95% CI, 0.86-3.99).

Conclusions: Having a serious mental illness is associated with higher rates of post-operative complications and longer stays in hospital, but not with higher in-hospital or 30-day mortality. Targeted pre-operative interventions may improve surgical outcomes for these vulnerable patients.

Abstract
Purpose: Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.

Methods: In this single-center trial, we examined the effect of a "KDIGO bundle" consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.

Results: AKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5-27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.

Conclusion: An implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.

Keywords: Acute kidney injury; Biomarkers; Cardiac surgery; KDIGO guidelines; Major adverse kidney events; [TIMP-2]·[IGFBP7].

Abstract
Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

ABSTRACT
Hand hygiene (HH) is comprehensively recognized to be the single most significant measure to prevent cross-transmission of microorganisms between patients. This study aimed to measure the HH compliance rates baseline, identify the barriers for HH non-compliance and to assess the impact of multidisciplinary intervention. An interventional study conducted from March 2017 to July 2017 in two surgical paediatric intensive care units (PICU) in two tertiary care hospitals. Root Cause Analysis (RCA) was used for identification of the barriers that affect HH compliance followed by intervention included HH training and education, video presentations in the hospital internal circuit, visual cues, using a code word for gentle verbal reminding and HH champions for follow up. Direct observation of HH was done before and after the intervention applying the WHO HH observation method. HH compliance rate was calculated by dividing the number of HH actions by the total number of opportunities. Chi-square (χ2) test was used to identify statistical significance. A total of 1735 HH opportunities were observed during all phases of the study. RCA identified skin dryness, forgetfulness and work intensity as the commonest barriers for non-compliance. Significant improvement was observed among all groups in PICU A (+23%; p value <0.001); (+19% for nurses, +29 % for doctors, and +36% for others; p value <0.001). While significant improvement was reported among doctors (+28%; p value <0.001) in PICU B. Improvement in HH compliance is achievable by multidisciplinary intervention. Providing continuous intensified training and feedback is essential to maintain high level of HH compliance.

Abstract
Background: Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes.

Methods: In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10-42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants.

Findings: Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78-1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68-1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints.

Interpretation: Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10-42 days before elective major abdominal surgery.

Abstract
Background and Objectives: Patients undergoing cardiac surgery are particularly vulnerable for developing postoperative pulmonary complications (PPCs). This systematic review and meta-analysis aimed to evaluate the role of preoperative chest physiotherapy in such patients. Materials and Methods: All original articles that assessed patients undergoing elective cardiac surgery, with preoperative chest physiotherapy, and compared them to patients undergoing elective cardiac surgery, without preoperative chest physiotherapy, were included. Animal studies, studies conducted prior to the year 2000, commentaries, or general discussion papers whose authors did not present original data were excluded. Studies assessing physiotherapy regimens other than chest physiotherapy were also excluded. The search was performed using the following electronic resources: the Cochrane Central Register of Controlled Trials, the PubMed central database, and Embase. The included studies were assessed for potential bias using the Cochrane Collaboration's tool for assessing the risk of bias. Each article was read carefully, and any relevant data were extracted. The extracted data were registered, tabulated, and analyzed using Review Manager software. Results: A total of 10 articles investigating 1458 patients were included in the study. The studies were published from 2006 to 2019. The populations were patients scheduled for elective CABG/cardiac surgery, and they were classified into two groups: the interventional (I) group, involving 651 patients, and the control (C) group, involving 807 patients. The meta-analysis demonstrated no significant differences between the interventional and control groups in surgery time and ICU duration, but a significant difference was found in the time of mechanical ventilation and the length of hospital stay, favoring the interventional group. A significant difference was shown in the forced expiratory volume in 1s (FEV1% predicted), forced vital capacity (FVC% predicted), and maximum inspiratory pressure (Pi-max), favoring the interventional group. Conclusions: This study is limited by the fact that one of the included ten studies was not an RCT. Moreover, due to lack of the assessment of certain variables in some studies, the highest number of studies included in a meta-analysis was the hospital stay length (eight studies), and the other variables were analyzed in a fewer number of studies. The data obtained can be considered as initial results until more inclusive RCTs are conducted involving a larger meta-analysis. However, in the present study, the intervention was proved to be protective against the occurrence of PPCs. The current work concluded that preoperative chest physiotherapy can yield better outcomes in patients undergoing elective cardiac surgery.

Abstract
Nutritional support, including oral nutritional supplements, enteral tube feeding and parenteral nutrition, can be an important part of the management of any patient. Malnutrition is common and costly, clinically and financially, if left untreated. In patients with, or at risk of, malnutrition, the appropriate use of nutritional support can prevent complications arising, produce other clinical, functional and financial benefits, and can be life saving in some situations. This article discusses the evidence from systematic reviews and meta-analyses of the effectiveness of nutritional support.

Abstract
Background: The increasing prevalence of frailty with age is becoming a public health priority in countries with ageing populations. Pre-frailty presents a window of opportunity to prevent the development of frailty in community-dwelling older adults. This study aimed to examine the effectiveness of a complex intervention that combined a nutrition-based intervention and a physical activity intervention, along with the effectiveness of each intervention individually, to reduce physical frailty in pre-frail older adults over 2 years.

Methods: In this single-blind, 2 x 2 factorial, randomised, controlled trial, we recruited pre-frail community-dwelling older adults in Aotearoa New Zealand via mail through general medical practices. To be eligible, participants had to be pre-frail according to self-reported FRAIL scores of 1 or 2, aged 75 years or older (or 60 years or older for Māori and Pacific Peoples), not terminally ill or with advanced dementia as judged by a general practitioner, able to stand, medically safe to participate in low-intensity exercise, and able to use kitchen utensils safely. Participants were randomly allocated to receive an 8-week Senior Chef programme (SC group), a 10-week Steady As You Go programme (SAYGO group), a 10-week combined SC and SAYGO intervention (combined group), or a 10-week social programme (control group), using computer-generated block randomisation administered through an electronic data capture system by local study coordinators. Assessors were masked to group allocation for all assessments. SC is a group-based nutrition education and cooking class programme (3 h weekly), SAYGO is a group-based strength and balance exercise programme (1 h weekly), and the social control programme was a seated, group socialising activity (once a week). Masked assessors ascertained Fried frailty scores at baseline, end of intervention, and at 6, 12, and 24 months after the programme. The primary outcome was change in Fried frailty score at 2 years. Intention-to-treat analyses were completed for all randomised participants, and all participants who had a high (≥75%) adherence were analysed per protocol. This study is registered at ANZCTR, ACTRN12614000827639.

Findings: Between May 12, 2016 and April 9, 2018, we assessed 2678 older adults for eligibility, of whom 468 (17%) consented and completed baseline assessment, with a mean age of 80·3 years (SD 5·1) and a mean Fried score of 1·9 (1·2); 59% were women. We randomly allocated these participants into the four groups: 117 in the SC group, 118 in the SAYGO group, 118 in the combined group, and 115 in the control group; 318 participants attended the 24-month follow-up: 89 in the SC group, 78 in the SAYGO group, 73 in the combined group, and 78 in the control group. At the 24-month follow-up, there were no differences in mean Fried scores between the intervention groups and the control group. No adverse events were reported.

Interpretation: The study did not find that the combined SC and SAYGO programme was effective in reducing frailty in pre-frail older adults. Although some short-term benefits were observed in each individual programme, there was no clear evidence of long-term impact. Further research is needed to evaluate combinations of group-based programmes for community-dwelling older adults to optimise their physical function.

Funding: Health Research Council New Zealand and Ageing Well Challenge (Ministry of Business Innovation and Employment).

Abstract
Frailty is increasingly recognized as a better predictor of adverse postoperative events than chronological age. The objective of this review was to systematically evaluate the effect of frailty on postoperative morbidity and mortality. Studies were included if patients underwent non-cardiac surgery and if frailty was measured by a validated instrument using physical, cognitive and functional domains. A systematic search was performed using EMBASE, MEDLINE, Web of Science, CENTRAL and PubMed from 1990 - 2017. Methodological quality was assessed using an assessment tool for prognosis studies. Outcomes were 30-day mortality and complications, one-year mortality, postoperative delirium and discharge location. Meta-analyses using random effect models were performed and presented as pooled risk ratios with confidence intervals and prediction intervals. We included 56 studies involving 1.106.653 patients. Eleven frailty assessment tools were used. Frailty increases risk of 30-day mortality (31 studies, 673.387 patients, risk ratio 3.71 [95% CI 2.89-4.77] (PI 1.38-9.97; I2=95%) and 30-day complications (37 studies, 627.991 patients, RR 2.39 [95% CI 2.02-2.83). Risk of 1-year mortality was threefold higher (six studies, 341.769 patients, RR 3.40 [95% CI 2.42-4.77]). Four studies (N=438) reported on postoperative delirium. Meta-analysis showed a significant increased risk (RR 2.13 [95% CI 1.23-3.67). Finally, frail patients had a higher risk of institutionalization (10 studies, RR 2.30 [95% CI 1.81- 2.92]). Frailty is strongly associated with risk of postoperative complications, delirium, institutionalization and mortality. Preoperative assessment of frailty can be used as a tool for patients and doctors to decide who benefits from surgery and who doesn't.

Abstract
Background: Daily smokers and hazardous drinkers are high-risk patients, developing 2-4 times more complications after surgery. Preoperative smoking and alcohol cessation for four to eight weeks prior to surgery halves this complication rate. The patients' preoperative contact with the surgical departments might be too brief for the hospital to initiate these programmes. Therefore, it was relevant to evaluate a new clinical practice which combined the general practitioner's (GP) referral to surgery with a referral to a smoking and alcohol intervention in the surgical pathway.

Methods: The design was an exploratory prospective trial. The outcome measured was the number of patients referred to a preoperative smoking and alcohol cessation programme at the same time as being referred for elective surgery by their GP. The participants consisted of 72 high-risk patients who were referred for elective surgery by 47 local participating GPs. The GPs, nurses, and specialists in internal medicine, prehabilitation and surgery developed new clinical practice guidelines based on the literature and interviews with 11 local GPs about the specific barriers for implementing a smoking and alcohol cessation programme. The role of the GP was to be the gatekeeper: identifying daily smokers and hazardous drinkers when referring them to surgery; handing out information on risk reduction; and referring those patients identified to a preoperative smoking and alcohol cessation programme. The role of the hospital was to contact these patients to initiate smoking and alcohol cessation at the hospital out-patient clinic for life-style intervention.

Results: The GPs increased their referral to the smoking and alcohol cessation programme from 0% to 10% (7/72 patients) in the study period.

Conclusion: The effect of the study was limited in integrating the efforts of primary care providers and hospital surgical departments in increasing the up-take of preoperative smoking and alcohol cessation programmes aimed at smokers and harmful drinkers referred for surgery. New strategies for cooperation between GPs and surgical departments are urgently needed.

Abstract
Background and purpose - There is a large volume of heterogeneous studies across all Enhanced Recovery After Surgery (ERAS®) components within total hip and total knee replacement surgery. This multidisciplinary consensus review summarizes the literature, and proposes recommendations for the perioperative care of patients undergoing total hip replacement and total knee replacement with an ERAS program.Methods - Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials, and large prospective cohort studies that evaluated the efficacy of individual items of the perioperative treatment pathway to expedite the achievement of discharge criteria. A consensus recommendation was reached by the group after critical appraisal of the literature.Results - This consensus statement includes 17 topic areas. Best practice includes optimizing preoperative patient education, anesthetic technique, and transfusion strategy, in combination with an opioid-sparing multimodal analgesic approach and early mobilization. There is insufficient evidence to recommend that one surgical technique (type of approach, use of a minimally invasive technique, prosthesis choice, or use of computer-assisted surgery) over another will independently effect achievement of discharge criteria.Interpretation - Based on the evidence available for each element of perioperative care pathways, the ERAS® Society presents a comprehensive consensus review, for the perioperative care of patients undergoing total hip replacement and total knee replacement surgery within an ERAS® program. This unified protocol should now be further evaluated in order to refine the protocol and verify the strength of these recommendations.

Abstract
Purpose: To evaluate the role of prehabilitation interventions in adult patients before elective major surgery.

Recent findings: Exercise training before elective adult major surgery is feasible and safe. Efficacy has been determined but the clinical effectiveness remains uncertain. Early data suggest a reduction in morbidity, length of stay, and an improvement in the quality of life. Nutritional and psychological interventions are less well evaluated, and when they are, it is often in combination with exercise interventions as part of multimodal prehabilitation.

Summary: Studies evaluating multimodal prehabilitation interventions before elective major surgery in adults are producing encouraging early results, but definitive clinical effectiveness is currently very limited. Future research should focus on refining interventions, exploring mechanisms, establishing minimum dosage, interrogating interactions between therapies, and urgent implementation of large-scale clinical effectiveness studies.

Abstract
Although much is known about surgical risk, little evidence exists regarding how best to proactively address preoperative risk factors to improve surgical outcomes. Preoperative malnutrition is a widely prevalent and modifiable risk factor in patients undergoing surgery. Malnutrition prior to surgery portends significantly higher postoperative mortality, morbidity, length of stay, readmission rates, and hospital costs. Unfortunately, perioperative malnutrition is poorly screened for and remains largely unrecognized and undertreated-a true "silent epidemic" in surgical care. To better address this silent epidemic of surgical nutrition risk, here we describe the rationalization, development, and implementation of a multidisciplinary, registered dietitian-driven, preoperative nutrition optimization clinic program designed to improve perioperative outcomes and reduce cost. Implementation of this novel Perioperative Enhancement Team (POET) Nutrition Clinic required a collaboration among many disciplines, as well as an identified need for multidimensional scheduling template development, data tracking systems, dashboard development, and integration of electronic health records. A structured malnutrition risk score (Perioperative Nutrition Screen score) was developed and is being validated. A structured malnutrition pathway was developed and is under study. Finally, the POET Nutrition Clinic has established a novel role for a perioperative registered dietitian as the integral point person to deliver perioperative nutrition care. We hope this structured model of perioperative nutrition assessment and optimization will allow for wide implementation and generalizability in other centers worldwide to improve recognition and treatment of perioperative nutrition risk.

Abstract
Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

Abstract
Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.

Abstract
Introduction: Diabetes has an increasing worldwide prevalence. It is known to be a predisposing factor for postoperative complications. Preoperative glycaemic control strategies should be pursued as glycaemic control could serve as a modifiable risk factor. Glycated haemoglobin (HbA1c), a marker of 3-month average glycaemic control, has been shown in meta-analyses to predict postoperative complications in cardiothoracic, bariatric and orthopaedic surgery. However, there is no meta-analysis in the major abdominal surgery population, in whom morbidity may be higher due to the nature of the surgery. Understanding the association between HbA1c and postoperative complications could help in preoperative risk prognostication, counselling and glycaemic target selection. The aim of this systematic review and meta-analysis is to evaluate all evidence on the association between preoperative HbA1c and postoperative complications in elective major abdominal surgery, and to investigate the threshold HbA1c level before postoperative complication rates increase.

Methods and analysis: This review will be performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar and China National Knowledge Infrastructure will be searched for all original studies. Study selection, data extraction, risk of bias and quality assessment will be conducted by two independent reviewers. The primary outcome is the association between preoperative HbA1c and major postoperative complications (Clavien Dindo 3-5), and the secondary outcome is the association between HbA1c and overall postoperative complications. Data management and synthesis will be performed using Microsoft Excel and Stata to derive pool estimates.

Ethics and dissemination: No ethics approval is required as only secondary data will be used. Findings will be disseminated through peer-reviewed journals and conference presentations.