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Worldviews on Evidence-based Nursing Oct 2021Postoperative delirium is the most common complication of surgery particularly in older patients. (Review)
Review
BACKGROUND
Postoperative delirium is the most common complication of surgery particularly in older patients.
AIMS
The current study aimed to summarize the commonly used delirium assessment tools in assessing postoperative delirium (POD) and to estimate the incidence rates of POD.
METHODS
A systematic review that included empirical cohort studies reporting the use of delirium assessment tools in assessing POD between 2000 and 2019. Five core databases were searched for eligible studies. The methodological quality assessment of the included studies was undertaken using the Joanna Briggs Institute (JBI) critical appraisal checklist to examine the risk of bias. Pooled incidence estimates were calculated using a random effects model.
RESULTS
Nineteen studies with a total of 3,533 postsurgery older patients were included in this review. The confusion assessment method (CAM) and CAM-ICU were the most commonly used tools to assess POD among older postoperative patients. The pooled incidence rate of POD was 24% (95% CI [0.20, 0.29]). The pooled incidence estimates for mixed (noncardiac) surgery, orthopedic surgery, and tumor surgery were 23% (95% CI [0.15, 0.31]), 27% (95% CI [0.20, 0.33]), and 19% (95% CI [0.15, 0.22]), respectively. More than 50% of included studies used CAM to assess POD in different types of postoperative patients. Using CAM to assess delirium is less time-consuming and it was suggested as the most efficient tool for POD detection.
LINKING EVIDENCE TO ACTION
We identified that CAM could be implemented in different settings for assessing POD. The incidence and risk factors for POD introduced can be used for future research to target these potential indicators. The incidence rate, risk factors, and predictors of POD explored can provide robust evidence for clinical practitioners in their daily practice.
Topics: Aged; Checklist; Cohort Studies; Delirium; Humans; Incidence; Risk Factors
PubMed: 34482593
DOI: 10.1111/wvn.12536 -
Journal of Psychiatric Research Jan 2021Melatonin, a pineal gland hormone is reported to have a protective effect against delirium. This systematic review and meta-analysis explores the effect of melatonin and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Melatonin, a pineal gland hormone is reported to have a protective effect against delirium. This systematic review and meta-analysis explores the effect of melatonin and melatonin receptor agonist, ramelteon on delirium prevention in adult hospitalized patients.
METHODS
Randomized Controlled trials of melatonin/ramelteon published up to May 7, 2020 were identified from MEDLINE, PREMEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled trials, PubMed, and Google Scholar. The primary outcome was delirium incidence. The secondary outcomes were sleep quality, sedation score, sedatives requirement, delirium duration, length of hospital stay, length of Intensive Care Unit (ICU) stay, mortality and adverse events. A meta-analysis with a random-effects models was performed. Estimates were presented as Risk Ratio (RR) or Mean Differences (MD) with 95% Confidence Interval (CI).
FINDINGS
Fourteen studies with 1712 participants were included. Melatonin/ramelteon significantly reduced delirium incidence (RR 0·61, 95% CI 0·42-0·89, p 0·009) with risk reduction of 49% in surgical patients and 34% in ICU patients. Non-significant reduction was found in medical patients. Melatonin/ramelteon were associated with improvement in sleep quality, increased sedation score and lower sedatives consumption. However, they did not reduce delirium duration, length of hospital stay, length of ICU stay and mortality. Hallucinations, nightmares and gastrointestinal disorders were prevalent in melatonin group.
INTERPRETATION
Melatonin/ramelteon are associated with reduction in delirium incidence in hospitalized patients. However, this effect seems confined to surgical and ICU patients. The optimum dosage and formulation of melatonin, and treatment duration remain uncleared and open to further studies with larger sample sizes.
Topics: Adult; Delirium; Humans; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Melatonin
PubMed: 33348252
DOI: 10.1016/j.jpsychires.2020.12.020 -
British Journal of Anaesthesia Feb 2023Postoperative delirium (POD) is the most common serious postoperative complication in older adults. It has uncertain aetiology, limited preventative strategies, and poor... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative delirium (POD) is the most common serious postoperative complication in older adults. It has uncertain aetiology, limited preventative strategies, and poor long-term outcomes. This updated systematic review and meta-analysis aimed to estimate the effect of processed electroencephalography (pEEG)-guided general anaesthesia during surgery on POD incidence.
METHODS
We performed a systematic review and meta-analysis by searching OVID MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. Studies of adult patients having general anaesthesia for any surgery where pEEG was used and POD was an outcome measure were included. Full-text reports of RCTs published from database inception until August 28, 2021, were included. Trials were excluded if sedation rather than general anaesthesia was administered, or the setting was intensive care. The primary outcome was POD assessed by validated tools. The study was prospectively registered with PROSPERO.
RESULTS
Nine studies, which included 4648 eligible subjects, were identified. The incidence of POD in the pEEG-guided general anaesthesia or lighter pEEG target group was 19.0% (440/2310) compared with 23.3% (545/2338) in the usual care or deeper pEEG target group (pooled odds ratio=0.78; 95% confidence interval, 0.60-1.00; P=0.054). Significant heterogeneity was detected (I=53%).
CONCLUSIONS
Our primary analysis demonstrated a highly sensitive result with a pooled analysis of trials in which the intervention group adhered to manufacturer's recommended guidelines, showing reduced incidence of POD with pEEG guidance. High clinical heterogeneity limits inferences from this and any future meta-analyses.
CLINICAL TRIAL REGISTRATION
CRD42020199404 (PROSPERO).
Topics: Humans; Aged; Emergence Delirium; Anesthesia, General; Postoperative Complications; Electroencephalography
PubMed: 35183345
DOI: 10.1016/j.bja.2022.01.006 -
Intensive & Critical Care Nursing Feb 2023Does early mobilisation as standalone or part of a bundle intervention, compared to usual care, prevent and/or shorten delirium in adult patients in Intensive Care Units? (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Does early mobilisation as standalone or part of a bundle intervention, compared to usual care, prevent and/or shorten delirium in adult patients in Intensive Care Units?
BACKGROUND
Early mobilisation is recommended for the prevention and treatment of delirium in critically ill patients, but the evidence remains inconclusive.
METHOD
Systematic literature search in Pubmed, CINAHL, PEDRo, Cochrane from inception to March 2022, and hand search in previous meta-analysis. Included were randomized trials or quality-improvement projects. meta-analysis was performed for Odds Ratios or mean differences including 95% Confidence Intervals for presence/duration of delirium. Risk of bias was assessed by using Joanna Briggs Quality criteria. meta-regression was performed to analyse heterogeneity.
RESULTS
The search led to 13 studies of low-moderate risk of bias including 2,164 patients. Early mobilisation reduced the risk of delirium by 47 % (13 studies, 2,164 patients, low to moderate risk of bias: Odds Ratio 0.53 (95 % Confidence Interval 0.34 till 0.83, p = 0.01), with significant heterogeneity (I = 78 %, p < 0.001). Early mobilisation also reduced the duration of delirium by 1.8 days (3 studies, 296 patients, low-moderate risk of bias: Mean difference -1.78 days (95 % Confidence Interval -2.73 till -0.83 days, p < 0.001), heterogeneity 0 % (p = 0.41). Other analyses such as low risk of bias studies, randomised trials, studies published ≥ 2017, high intensity, and mobilisation as stand-alone intervention showed no significant results, with conflicting certainty of evidence and high heterogeneity. meta-regression could not explain heterogeneity.
CONCLUSION
There is an uncertain effect of mobilisation on delirium. Provision of early mobilisation to critical ill patients might prevent delirium. There is a possible effect of early mobilisation to shorten the duration of delirium. Due to the heterogeneity in the findings, further research to define the best method and dosage of early rehabilitation is required.
Topics: Adult; Humans; Critical Illness; Delirium; Early Ambulation; Physical Therapy Modalities
PubMed: 37440187
DOI: 10.1016/j.iccn.2022.103334 -
Journal of Psychiatric Research Jun 2020We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of... (Meta-Analysis)
Meta-Analysis Review
We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Network Meta-Analysis; Risperidone
PubMed: 32302794
DOI: 10.1016/j.jpsychires.2020.03.012 -
The Cochrane Database of Systematic... Jul 2021Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious adverse outcomes. Treatment options for established delirium are limited and so prevention of delirium is desirable. Non-pharmacological interventions are thought to be important in delirium prevention. OBJECTIVES: To assess the effectiveness of non-pharmacological interventions designed to prevent delirium in hospitalised patients outside intensive care units (ICU).
SEARCH METHODS
We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP to 16 September 2020. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of single and multicomponent non-pharmacological interventions for preventing delirium in hospitalised adults cared for outside intensive care or high dependency settings. We only included non-pharmacological interventions which were designed and implemented to prevent delirium. DATA COLLECTION AND ANALYSIS: Two review authors independently examined titles and abstracts identified by the search for eligibility and extracted data from full-text articles. Any disagreements on eligibility and inclusion were resolved by consensus. We used standard Cochrane methodological procedures. The primary outcomes were: incidence of delirium; inpatient and later mortality; and new diagnosis of dementia. We included secondary and adverse outcomes as pre-specified in the review protocol. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes and between-group mean differences for continuous outcomes. The certainty of the evidence was assessed using GRADE. A complementary exploratory analysis was undertaker using a Bayesian component network meta-analysis fixed-effect model to evaluate the comparative effectiveness of the individual components of multicomponent interventions and describe which components were most strongly associated with reducing the incidence of delirium.
MAIN RESULTS
We included 22 RCTs that recruited a total of 5718 adult participants. Fourteen trials compared a multicomponent delirium prevention intervention with usual care. Two trials compared liberal and restrictive blood transfusion thresholds. The remaining six trials each investigated a different non-pharmacological intervention. Incidence of delirium was reported in all studies. Using the Cochrane risk of bias tool, we identified risks of bias in all included trials. All were at high risk of performance bias as participants and personnel were not blinded to the interventions. Nine trials were at high risk of detection bias due to lack of blinding of outcome assessors and three more were at unclear risk in this domain. Pooled data showed that multi-component non-pharmacological interventions probably reduce the incidence of delirium compared to usual care (10.5% incidence in the intervention group, compared to 18.4% in the control group, risk ratio (RR) 0.57, 95% confidence interval (CI) 0.46 to 0.71, I = 39%; 14 studies; 3693 participants; moderate-certainty evidence, downgraded due to risk of bias). There may be little or no effect of multicomponent interventions on inpatient mortality compared to usual care (5.2% in the intervention group, compared to 4.5% in the control group, RR 1.17, 95% CI 0.79 to 1.74, I = 15%; 10 studies; 2640 participants; low-certainty evidence downgraded due to inconsistency and imprecision). No studies of multicomponent interventions reported data on new diagnoses of dementia. Multicomponent interventions may result in a small reduction of around a day in the duration of a delirium episode (mean difference (MD) -0.93, 95% CI -2.01 to 0.14 days, I = 65%; 351 participants; low-certainty evidence downgraded due to risk of bias and imprecision). The evidence is very uncertain about the effect of multicomponent interventions on delirium severity (standardised mean difference (SMD) -0.49, 95% CI -1.13 to 0.14, I=64%; 147 participants; very low-certainty evidence downgraded due to risk of bias and serious imprecision). Multicomponent interventions may result in a reduction in hospital length of stay compared to usual care (MD -1.30 days, 95% CI -2.56 to -0.04 days, I=91%; 3351 participants; low-certainty evidence downgraded due to risk of bias and inconsistency), but little to no difference in new care home admission at the time of hospital discharge (RR 0.77, 95% CI 0.55 to 1.07; 536 participants; low-certainty evidence downgraded due to risk of bias and imprecision). Reporting of other adverse outcomes was limited. Our exploratory component network meta-analysis found that re-orientation (including use of familiar objects), cognitive stimulation and sleep hygiene were associated with reduced risk of incident delirium. Attention to nutrition and hydration, oxygenation, medication review, assessment of mood and bowel and bladder care were probably associated with a reduction in incident delirium but estimates included the possibility of no benefit or harm. Reducing sensory deprivation, identification of infection, mobilisation and pain control all had summary estimates that suggested potential increases in delirium incidence, but the uncertainty in the estimates was substantial. Evidence from two trials suggests that use of a liberal transfusion threshold over a restrictive transfusion threshold probably results in little to no difference in incident delirium (RR 0.92, 95% CI 0.62 to 1.36; I = 9%; 294 participants; moderate-certainty evidence downgraded due to risk of bias). Six other interventions were examined, but evidence for each was limited to single studies and we identified no evidence of delirium prevention. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence regarding the benefit of multicomponent non-pharmacological interventions for the prevention of delirium in hospitalised adults, estimated to reduce incidence by 43% compared to usual care. We found no evidence of an effect on mortality. There is emerging evidence that these interventions may reduce hospital length of stay, with a trend towards reduced delirium duration, although the effect on delirium severity remains uncertain. Further research should focus on implementation and detailed analysis of the components of the interventions to support more effective, tailored practice recommendations.
Topics: Aged; Aged, 80 and over; Bias; Blood Transfusion; Combined Modality Therapy; Delirium; Hospital Mortality; Humans; Incidence; Inpatients; Length of Stay; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 34280303
DOI: 10.1002/14651858.CD013307.pub2 -
Anesthesia and Analgesia Aug 2021Both frailty and postoperative delirium (POD) are common in elective surgical patients 65 years of age and older. However, the association between preoperative frailty... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both frailty and postoperative delirium (POD) are common in elective surgical patients 65 years of age and older. However, the association between preoperative frailty and POD remains difficult to characterize owing to the large number of frailty and POD assessment tools used in the literature, only a few of which are validated. Furthermore, some validated frailty tools fail to provide clear score cutoffs for distinguishing frail and nonfrail patients. We performed a meta-analysis to estimate the relationship between preoperative frailty and POD.
METHODS
We searched several major databases for articles that investigated the relationship between preoperative frailty and POD in patients with mean age ≥65 years who were undergoing elective, nonemergent inpatient surgery. Inclusion criteria included articles published in English no earlier than 1999. Both preoperative frailty and POD must have been measured with validated tools using clear cutoff scores for frailty and delirium. Articles were selected and data extracted independently by 2 researchers. Risk of bias (ROBINS-I) and presence of confounders were summarized. Odds ratios (ORs) for POD associated with frailty relative to nonfrailty were computed with adjusted ORs when available. Original estimates were pooled by random effects analysis. Statistical significance was set at 2-sided P < .05.
RESULTS
Nine studies qualified for meta-analysis. The Fried score or a modified version of it was used in 5 studies. Frailty prevalence ranged from 18.6% to 56%. Delirium was assessed with the Confusion Assessment Method (CAM) or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in 7 studies, Delirium Observation Scale in 1 study, and Intensive Care Delirium Screening Checklist in 1 study. The incidence of POD ranged from 7% to 56%. ROBINS-I risk of bias was low in 1 study, moderate in 4 studies, serious in 3 studies, and critical in 1 study. Random effects analysis (n = 794) of the OR for POD in frail versus nonfrail patients based on adjusted OR estimates was significant with an OR of 2.14 and a 95% confidence interval of 1.43-3.19. The I2 value was in the low range at 5.5, suggesting small variability from random effects. Funnel-plot analysis did not definitively support either the presence or absence of publication bias.
CONCLUSIONS
This meta-analysis provides evidence for a significant association between preoperative frailty and POD in elective surgical patients age 65 years or older.
Topics: Age Factors; Aged; Delirium; Elective Surgical Procedures; Female; Frail Elderly; Frailty; Humans; Incidence; Male; Postoperative Cognitive Complications; Prevalence; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 34257192
DOI: 10.1213/ANE.0000000000005609 -
Journal of Clinical Nursing May 2023To identify the most accurate postoperative delirium screening tools for detecting postoperative delirium among patients who underwent general anaesthesia surgery in... (Meta-Analysis)
Meta-Analysis Review
AIMS AND OBJECTIVES
To identify the most accurate postoperative delirium screening tools for detecting postoperative delirium among patients who underwent general anaesthesia surgery in general wards.
BACKGROUND
The lack of detection of postoperative delirium can negatively affect the patient's condition, along with their postoperative treatment and rehabilitation, and it can prolong their hospitalisation, persists cognitive dysfunction and increases mortality. Screening for postoperative delirium in hospitalised patients as nursing assessment is routine clinical practice for early detection.
DESIGN
A systematic review and meta-analysis.
METHODS
MEDLINE, Embase, CINAHL, KoreaMed and Cochrane electronic databases were searched using the key words delirium, postoperative, assessment or screening, and adult for articles published up to April 2020, with no limit on the year of publishing. Only prospective cohort studies reporting sensitivity and specificity values were included. We followed the recommendations of the Cochrane Handbook of Diagnostic Test Accuracy Reviews and the PRISMA checklist. The Quality Assessment of the Diagnostic Accuracy Studies-2 tool was used for data extraction and quality assessment, while a bivariate random-effects meta-analysis model was used for pooling and comparing diagnostic accuracy and providing a summary of evidence.
RESULTS
Six delirium assessment tools were evaluated from nine papers including 3088 patients. Due to the limited number of papers, the meta-analysis included the Confusion Assessment Method (CAM) and its variants, Delirium Detection Score (DDS) and Nurses' Delirium Screening Checklist (NuDESC). Overall, NuDESC demonstrated higher sensitivity than CAM or DDS, while all showed high specificity (0.90 or greater).
CONCLUSION
This review suggested that NuDESC can be employed as an accurate screening tool with high specificity for assessing postoperative delirium during routine checkups. However, it is necessary to consider suitable cut-off values, which is the reference point, in accordance with the clinical setting and the patients' condition.
RELEVANCE TO CLINICAL PRACTICE
NuDESC reported the best evidence of diagnostic accuracy, and we recommend clinical nurses to employ this easy-to-use and validated tool for daily screening of postoperative delirium in general wards to facilitate its early detection and the accurate estimation of its prevalence.
Topics: Humans; Adult; Emergence Delirium; Delirium; Prospective Studies; Anesthetics; Anesthesia, General
PubMed: 34881476
DOI: 10.1111/jocn.16157 -
Medicina Intensiva Apr 2020Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new...
Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.
Topics: Analgesia; Anesthesia; Benzodiazepines; Conscious Sedation; Critical Care; Critical Illness; Delirium; Evidence-Based Medicine; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Pain Management
PubMed: 31492476
DOI: 10.1016/j.medin.2019.07.013 -
British Journal of Anaesthesia Feb 2023Systematic reviews to date have neglected to exclusively include studies using a validated diagnostic scale for postoperative delirium and monitoring patients for more... (Meta-Analysis)
Meta-Analysis Review
Perioperative risk factors associated with increased incidence of postoperative delirium: systematic review, meta-analysis, and Grading of Recommendations Assessment, Development, and Evaluation system report of clinical literature.
BACKGROUND
Systematic reviews to date have neglected to exclusively include studies using a validated diagnostic scale for postoperative delirium and monitoring patients for more than 24 h. Evidence on current risk factors is evolving with significantly heterogeneous study designs, inconsistent reporting of results, and a lack of adjustment for bias.
METHODS
This systematic review and meta-analysis aimed to identify risk factors for postoperative delirium in an adult patient population. Study designs suitable for this review included full-text articles, RCTs, observational studies, cohort studies, and case-control studies. Extracted variables from the 169 (7.4%) selected studies were included in qualitative synthesis, quantitative synthesis, and a postoperative delirium checklist. The 16 variables included in the checklist were selected based on consistency, direction of effect, number of studies, and clinical utility as a reference for future studies.
RESULTS
A total of 576 variables were extracted, but only six were eligible for meta-analysis. Age (mean difference [MD]=4.94; 95% confidence interval [CI], 2.93-6.94; P<0.001), American Society of Anesthesiologists physical status >2 (odds ratio [OR]=2.27; 95% CI, 1.47-3.52; P<0.001), Charlson Comorbidity Index ≥2 (OR=1.9; 95% CI, 1.11-3.25; P=0.0202), and Mini-Mental State Examination (MD=-1.94; 95% CI, -3.6 to -0.27; P=0.0224) were statistically significant.
CONCLUSIONS
Risk factors can assist in clinical decision-making and identification of high-risk patients. Literature analysis identified inconsistent methodology, leading to challenges in interpretation. A standardised format and evidence-based approach should guide future studies.
Topics: Adult; Humans; Emergence Delirium; Incidence; Risk Factors; Bias; Case-Control Studies; Observational Studies as Topic
PubMed: 35810005
DOI: 10.1016/j.bja.2022.05.032