Focused transoesophageal TOE (fTOE): A new accreditation pathway.

The concept of a focused ultrasound study to identify sources of haemodynamic instability has revolutionized patient care. Point-of-care ultrasound (POCUS) using transthoracic scanning protocols, such as FUSIC Heart, has empowered non-cardiologists to rapidly identify and treat the major causes of haemodynamic instability. There are, however, circumstances when a transoesphageal, rather than transthoracic approach, may be preferrable. Due to the close anatomical proximity between the oesophagus, stomach and heart, a transoesphageal echocardiogram (TOE) can potentially overcome many of the limitations encountered in patients with poor transthoracic ultrasound windows. These are typically patients with severe obesity, chest wall injuries, inability to lie in the left lateral decubitus position and those receiving high levels of positive airway pressure. In 2022, to provide all acute care practitioners with the opportunity to acquire competency in focused TOE, the Intensive Care Society (ICS) and Association of Anaesthetists (AA) launched a new accreditation pathway, known as Focused Transoesophageal Echo (fTOE). The aim of fTOE is to provide the practitioner with the necessary information to identify the aetiology of haemodynamic instability. Focused TOE can be taught in a shorter period of time than comprehensive and teaching programmes are achievable with support from cardiothoracic anaesthetists, intensivists and cardiologists. Registration for fTOE accreditation requires registration via the ICS website. Learning material include theoretical modules, clinical cases and multiple-choice questions. Fifty fTOE examinations are required for the logbook, and these must cover a range of pathology, including ventricular dysfunction, pericardial effusion, tamponade, pleural effusion and low preload. The final practical assessment may be undertaken when the supervisors deem the candidate's knowledge and skills consistent with that required for independent practice. After the practitioner has been accredited in fTOE, they must maintain knowledge and competence through relevant continuing medical education. Accreditation in fTOE represents a joint venture between the ICS and AA and is endorsed by Association of Cardiothoracic Anaesthesia and Critical care (ACTACC). The process is led by TOE experts, and represents a valuable expansion in the armamentarium of acute care practitioners to assess haemodynamically unstable patients.

Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: a statistical analysis plan for NOTACS, a multicentre adaptive randomised controlled trial.

BACKGROUND: The NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery. METHODS/DESIGN: NOTACS is an adaptive, international, multicentre, parallel-group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1152 patients. RESULTS: This manuscript provides detailed descriptions of the design of the NOTACS trial, and the analyses to be undertaken at the interim and final analyses. The main purpose of the interim analysis is to assess safety and to perform a sample size re-estimation. The main purpose of the final analysis is to examine the safety, efficacy and cost-effectiveness of HFNT compared to SOT on the outcomes of patients after cardiac surgery. DISCUSSION: This manuscript outlines the key features of the NOTACS statistical analysis plan and was submitted to the journal before the interim analysis in order to preserve scientific integrity under an adaptive design framework. The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials. TRIAL REGISTRATION: ISRCTN14092678 . Registered on 13 May 2020.

Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study.

BACKGROUND: One in two adults undergoing cardiac surgery are iron deficient, best practice guidelines and consensus statements recommend routine investigation and treatment of iron deficiency before elective cardiac surgery, even in the absence of anaemia; however, it is not clear if non-anaemic iron deficiency is associated with worse outcomes in this patient population. We hypothesised that iron deficiency would be associated with worse postoperative outcomes than an iron replete state in adults without anaemia undergoing elective cardiac surgery. METHODS: We performed a prospective, cohort study at two hospitals in Australia. We recruited adults (ie, people 18 years and older) undergoing elective cardiac surgery without anaemia (defined as a haemoglobin of less than 130 g/L for men and less than 120 g/L for women), concomitant haemoglobinopathy, bone marrow pathology, haemochromatosis, or end-stage renal failure requiring dialysis. Participants were stratified as iron deficient or iron replete on the basis of preoperative testing. Iron deficiency was defined as a serum ferritin of less than 100 µg/L or 100-300 µg/L if transferrin saturation was less than 20% or C-reactive protein was more than 5 mg/L. The primary endpoint was days alive and at home at postoperative day 30. The primary analysis included all patients with data available for the primary endpoint and was adjusted for risk measured using EuroSCORE-II and body surface area. The study was prospectively registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12618000185268. FINDINGS: We conducted the study between Feb 21, 2018, and May 7, 2021. We assessed 1171 patients for eligibility and 691 were ineligible; therefore, we enrolled and followed up 480 participants. 240 (50%) were iron deficient and 240 (50%) were iron replete, 95 (20%) were women, 385 (80%) were men, and 453 (94%) were White. Complete data was available for 479 individuals (240 in the iron deficient group and 239 in the iron replete group) for the primary endpoint. The iron deficient group had a median of 22·87 days (IQR 20·65 to 24·06) alive and at home at postoperative day 30, and the iron replete group had a median of 23·18 days (IQR 20·69 to 24·70). The unadjusted difference in medians between the groups was -0·18 days (95% CI -0·73 to 0·36; p=0·51) and the adjusted difference in medians between the groups was -0·11 days (95% CI -0·66 to 0·45; p=0·70). INTERPRETATION: In non-anaemic adults undergoing elective cardiac surgery, our findings suggest that patients with iron deficiency do not have a reduction in days alive and at home at postoperative day 30 compared with patients who have a normal iron status. Routine preoperative investigation for iron deficiency in patients without anaemia undergoing elective cardiac surgery using the definitions we tested might be low-value care. FUNDING: Australian and New Zealand College of Anaesthetists Foundation.

Correcting the scientific record - A broken system?

The current system for assessing and publicly notifying concerns about publication integrity is slow, inefficient, inconsistent, inadequate, and opaque. Readers are, therefore, left unaware of potential issues about publications or are given inadequate information to assess publication integrity. We propose a new process for dealing with publication integrity involving the establishment of independent panel(s) that assess publication integrity and transparently report the outcomes of those assessments, independent of the assessment of any misconduct.

Preoperative intravenous iron before cardiac surgery: a prospective multicentre feasibility study.

BACKGROUND: Preoperative anaemia affects one third of patients undergoing cardiac surgery and is associated with increased mortality and morbidity. Although it is recommended that perioperative teams should identify and treat patients with preoperative anaemia before surgery, introducing new treatment protocols can be challenging in surgical pathways. The aim of this study was to assess the feasibility and effectiveness of introducing a preoperative intravenous iron service as a national initiative in cardiac surgery. METHODS: We performed a multicentre, stepped, observational study using the UK Association of Cardiothoracic Anaesthesia and Critical Care Research Network. The primary feasibility outcome was the ability to set up an anaemia and intravenous iron clinic at each site. The primary efficacy outcome was change in haemoglobin (Hb) concentration between intervention and operation. Secondary outcomes included blood transfusion and hospital stay. Patients with anaemia were compared with non-anaemic patients and with those who received intravenous iron as part of their routine treatment protocol. RESULTS: Seven out of 11 NHS hospitals successfully set up iron clinics over 2 yr, and 228 patients were recruited into this study. Patients with anaemia who received intravenous iron were at higher surgical risk, were more likely to have a known previous history of iron deficiency or anaemia, had a higher rate of chronic kidney disease, and were slightly more anaemic than the non-treated group. Intravenous iron was administered a median (inter-quartile range, IQR [range]) of 33 (15-53 [4-303]) days before surgery. Preoperative intravenous iron increased [Hb] from baseline to pre-surgery; mean (95% confidence interval) change was +8.4 (5.0-11.8) g L-1 (P<0.001). Overall, anaemic compared with non-anaemic patients were more likely to be transfused (49% [59/136] vs 27% (22/92), P=0.001) and stayed longer in hospital (median days [IQR], 9 [7-15] vs 8 [6-11]; P=0.014). The number of days alive and at home was lower in the anaemic group (median days [IQR], 20 [14-22] vs 21 [17-23]; P=0.033). CONCLUSION: The development of an intravenous iron pathway is feasible but appears limited to selected high-risk cardiac patients in routine NHS practise. Although intravenous iron increased [Hb], there is a need for an appropriately powered clinical trial to assess the clinical effect of intravenous iron on patient-centred outcomes.

The Association Between Pulsatile Cardiopulmonary Bypass and Acute Kidney Injury After Cardiac Surgery: A Before-and-After Study.

OBJECTIVES: To investigate the association between pulsatile perfusion and cardiac surgery-associated acute kidney injury. DESIGN: An uncontrolled, retrospective before-and-after study. SETTING: Single tertiary hospital. PARTICIPANTS: A total of 2,489 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Pulsatile versus nonpulsatile perfusion. MEASUREMENTS AND MAIN RESULTS: Data for nonpulsatile perfusion was collected from April 1, 2016, to March 31, 2017 (n = 1,223). A practice change to universal pulsatile CPB occurred on April 3, 2017. Data for pulsatile perfusion was collected from May 1, 2017, to June 30, 2018 (n = 1,266). The primary outcome was the incidence of acute kidney injury (AKI) after cardiac surgery. Multivariable analysis was carried out to adjust for known confounders. Secondary outcomes included AKI stage, stroke, length of stay, and mortality. Subgroup analyses were carried out using prolonged CPB and chronic kidney disease. The primary outcome, incidence of AKI, did not differ between the nonpulsatile control group and the pulsatile group (23.9% v 25.4%, p = 0.392). The pulsatile group was not associated with AKI in the multivariable analysis (Odds ratio 1.09, p = 0.413). There were no differences in stages of AKI in the nonpulsatile group v pulsatile group (13.6% v 14.9%, 2.9% v 4.3%, and 7.4% v 6.1% for stages 1, 2, and 3, respectively, p = 0.12). There were no differences in subgroup analyses or secondary outcomes. CONCLUSIONS: There was no association found between kidney injury and pulsatile perfusion. It is likely that there is either no association between pulsatile perfusion and reduced kidney injury or that the difference is extremely small.

The Effects of Escalation of Respiratory Support and Prolonged Invasive Ventilation on Outcomes of Cardiac Surgical Patients: A Retrospective Cohort Study.

OBJECTIVES: The aim of this study was to determine the effects of escalation of respiratory support and prolonged postoperative invasive ventilation on patient-centered outcomes, and identify perioperative factors associated with these 2 respiratory complications. DESIGN: A retrospective cohort analysis of cardiac surgical patients admitted to the cardiothoracic intensive care unit (ICU) between August 2015 and January 2018. Escalation of respiratory support was defined as "unplanned continuous positive airway pressure," "non-invasive ventilation," or "reintubation" after surgery; prolonged invasive ventilation was defined as "invasive ventilation beyond the first 12 hours following surgery." The primary endpoint was the composite of escalation of respiratory support and prolonged ventilation. SETTING: Tertiary cardiothoracic ICU. PARTICIPANTS: A total of 2,098 patients were included and analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The composite of escalation of support or prolonged ventilation occurred in 509 patients (24.3%). Patients who met the composite had higher mortality (2.9% v 0.1%; p < 0.001) and longer median [interquartile range] length of ICU (2.1 [1.0-4.9] v 0.9 [0.8-1.0] days; p < 0.0001) and hospital (10.6 [8.0-16.0] v 7.2 [6.2-10.0] days; p < 0.0001) stay. Hypoxemia and anemia on admission to ICU were the only 2 factors independently associated with the need for escalation of respiratory support or prolonged invasive ventilation. CONCLUSIONS: Escalation of respiratory support or prolonged invasive ventilation is frequently seen in cardiac surgery patients and is highly associated with increased mortality and morbidity. Hypoxemia and anemia on admission to the ICU are potentially modifiable factors associated with escalation of respiratory support or prolonged invasive ventilation.

Development and feasibility of a Patient Blood Management implementation programme in vascular surgery.

Vascular surgery is the largest (non-cardiac) user of blood transfusion which is associated with increased risk to patients. Patient Blood Management (PBM) is a quality improvement programme in transfusion medicine involving educational change and recommendations through preoperative, operative, and postoperative surgery. We wished to assess the feasibility to implement a PBM programme in vascular surgery. A multidisciplinary programme was developed at a vascular unit by PBM experts. The PBM programme involved a series of educational lectures, consultations, and discussions with doctors, nurses, and theatre staff. A one-page PBM checklist of recommendations was developed for all patients undergoing vascular surgery. Prospective audits were conducted before (October 2014 to March 2015) and after (November 2015 to February 2016) PBM implementation. Outcomes were blood transfusion and haemoglobin concentration (Hb) trigger threshold. A total of 211 patients were admitted under vascular surgery: 127 for Audit 1 and 84 for Audit 2. Overall, 30% of patients were transfused, with 193 units transfused in Audit 1 and 85 in Audit 2. PBM implementation was associated with a reduction in patients receiving a blood transfusion (37% to 20%; p = 0.01). However, there was no difference in Hb trigger threshold (76 g/L vs 72 g/L, p = 0.051). A PBM programme is feasible and can be implemented in vascular surgery. PBM was associated with an improvement in transfusion use and length of patient stay that merits further investigation.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis.

BACKGROUND: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use. CONCLUSIONS: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.

Randomized evaluation of fibrinogen versus placebo in complex cardiovascular surgery: post hoc analysis and interpretation of phase III results.

OBJECTIVES: In a multicentre, randomized-controlled, phase III trial in complex cardiovascular surgery (Randomized Evaluation of Fibrinogen vs Placebo in Complex Cardiovascular Surgery: REPLACE), single-dose human fibrinogen concentrate (FCH) was associated with the transfusion of increased allogeneic blood products (ABPs) versus placebo. Post hoc analyses were performed to identify possible reasons for this result. METHODS: We stratified REPLACE results by adherence to the transfusion algorithm, pretreatment fibrinogen level (≤2 g/l vs >2 g/l) and whether patients were among the first 3 treated at their centre. RESULTS: Patients whose treatment was adherent with the transfusion algorithm [FCH, n = 47 (60.3%); placebo, n = 57 (77.0%); P = 0.036] received smaller quantities of ABPs than those with non-adherent treatment (P < 0.001). Among treatment-adherent patients with pretreatment plasma fibrinogen ≤2 g/l, greater reduction in 5-min bleeding mass was seen with FCH versus placebo (median -22.5 g vs -15.5 g; P = 0.071). Considering patients with the above conditions and not among the first 3 treated at their centre (FCH, n = 15; placebo, n = 22), FCH was associated with trends towards reduced transfusion of ABPs (median 2.0 vs 4.0 units; P = 0.573) and greater reduction in 5-min bleeding mass (median -21.0 g vs -9.5 g; P = 0.173). Differences from a preceding single-centre phase II study with positive outcomes included more patients with pretreatment fibrinogen >2 g/l and fewer patients undergoing thoracoabdominal aortic aneurysm repair. CONCLUSIONS: None of the patient stratifications provided a clear explanation for the lack of efficacy seen for FCH in the REPLACE trial versus the positive phase II outcomes. However, together, the 3 factors demonstrated trends favouring FCH. Less familiarity with the protocol and procedures and unavoidable differences in the study populations may explain the differences seen between the phase II study and REPLACE. CLINICAL TRIAL REGISTRATION: NCT01475669 https://clinicaltrials.gov/ct2/show/NCT01475669; EudraCT trial no: 2011-002685-20.

Does the "Weekend Effect" for Postoperative Mortality Stand Up to Scrutiny? Association for Cardiothoracic Anesthesia and Critical Care Cohort Study of 110,728 Cardiac Surgical Patients.

OBJECTIVE: Ongoing debate focuses on whether patients admitted to the hospital on weekends have higher mortality than those admitted on weekdays. Whether this apparent "weekend effect" reflects differing patient risk, care quality differences, or inadequate adjustment for risk during analysis remains unclear. This study aimed to examine the existence of a "weekend effect" for risk-adjusted in-hospital mortality after cardiac surgery. DESIGN: Retrospective analysis of prospectively collected cardiac registry data. SETTING: Ten UK specialist cardiac centers. PARTICIPANTS: A total of 110,728 cases, undertaken by 127 consultant surgeons and 190 consultant anesthetists between April 2002 and March 2012. INTERVENTIONS: Major risk-stratified cardiac surgical operations. MEASUREMENTS AND MAIN RESULTS: Crude in-hospital mortality rate was 3.1%. Multilevel multivariable models were employed to estimate the effect of operative day on in-hospital mortality, adjusting for center, surgeon, anesthetist, patient risk, and procedure priority. Weekend elective cases had significantly lower mortality risk compared to Monday elective cases (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.42, 0.96) following risk adjustment by the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and procedure priority; differences between weekend and Monday for urgent and emergency/salvage cases were not significant (OR 1.12, 95% CI 0.73, 1.72, and 1.07, 95% CI 0.79, 1.45 respectively). Considering only the logistic EuroSCORE but not procedure priority yielded 29% higher odds of death for weekend cases compared to Monday operations (OR 1.29, 95% CI 1.08, 1.54). CONCLUSIONS: This study suggests that undergoing cardiac surgery during the weekend does not affect negatively patient survival, and highlights the importance of comprehensive risk adjustment to avoid detecting spurious "weekend effects."

Evaluation of the Clinical Utility of Transesophageal Echocardiography and Invasive Monitoring to Assess Right Ventricular Function During and After Pulmonary Endarterectomy.

OBJECTIVE: Patients undergoing pulmonary endarterectomy (PEA) have impaired right ventricular function. The authors sought to assess the clinical utility of commonly used perioperative echocardiographic and right heart catheter measurements in patients undergoing PEA. DESIGN: A single-center prospective observational study. SETTING: The study was conducted in a quaternary care cardiac surgical center in the United Kingdom. PARTICIPANTS: Patients undergoing PEA between April 2015 and January 2016. INTERVENTIONS: Thermodilution cardiac index and echocardiography variables were measured at 3 time points: before sternotomy (T1), after pericardial incision (T2), and after sternal closure (T3). Six-month follow-up echocardiography and 6-minute walk (6-MWT) test were performed. MEASUREMENTS AND MAIN RESULTS: Fifty patients were recruited and complete data sets were available for 41 patients. Tricuspid annular plane systolic excursion declined after pericardial incision and cardiopulmonary bypass (T1: 15 ± 4 mm, T2: 13 ± 4 mm, T3: 7 ± 2 mm; p < 0.0001), returning to baseline 6 months postoperatively. Cardiac index (T1: 2.5 ± 0.7 L/min/m2, T2: 2.6 ± 0.6 L/min/m2, T3: 2.3 ± 0.5 L/min/m2; p = 0.07) and right ventricular fractional area change (T1: 36 ± 11%, T2: 40 ± 12%, T3: 40 ± 9%; p = 0.12) were preserved perioperatively. 6-MWT improved from baseline (294 ± 111 m) to follow-up (357 ± 107 m) (p < 0.001). Pulmonary vascular resistance at T3 correlated moderately with follow-up 6-MWT (R = -0.60). CONCLUSIONS: In patients undergoing PEA, invasive measurements and echocardiography assessment of right ventricular function are not interchangeable. Tricuspid annular plane systolic excursion is not a reliable measure of right ventricular function perioperatively. Pulmonary vascular resistance shows moderate correlation with postoperative functional capacity.

Enhanced recovery for thoracic surgery in the elderly.

PURPOSE OF REVIEW: Both surgical workload and the age of those patients being considered for radial pulmonary resection are increasing. Enhanced recovery programmes are now well established in most surgical disciplines and are increasingly reported in thoracic procedures. This review will discuss the relevant principles of these programmes as applied to an increasing elderly population. RECENT FINDINGS: Elderly patients undergoing less radial surgical resections without lymphadenectomy have comparable outcomes to those undergoing classical curative treatment. Patients require careful assessment and self-reported quality of life metrics or function may be a better marker of outcome than static measures such as lung function. Hypotension, low values for bispectral index and low anaesthetic gas mean alveolar concentration values are common and independent predictors of mortality in the elderly. Paravertebral blockade is preferred to epidural anaesthesia because of a more favourable side-effect profile and comparable efficacy. As yet no robust work has examined the efficacy of an integrated enhanced recovery programme in thoracic surgery. SUMMARY: Elderly patients are suitable for enhanced recovery programmes but these must be tailored to individual circumstance. Further work is required to comprehensively assess their value in a modern healthcare setting.

Effect of individual patient risk, centre, surgeon and anaesthetist on length of stay in hospital after cardiac surgery: Association of Cardiothoracic Anaesthesia and Critical Care (ACTACC) consecutive cases series study of 10 UK specialist centres.

OBJECTIVES: To determine the relative contributions of patient risk profile, local and individual clinical practice on length of hospital stay after cardiac surgery. DESIGN: Ten-year audit of prospectively collected consecutive cardiac surgical cases. Case-mix adjusted outcomes were analysed in models that included random effects for centre, surgeon and anaesthetist. SETTING: UK centres providing adult cardiac surgery. PARTICIPANTS: 10 of 36 UK specialist centres agreed to provide outcomes for all major cardiac operations over 10 years. After exclusions (duplicates, cases operated by more than one consultant, deaths and procedures for which the EuroSCORE risk score for cardiac surgery is not appropriate), there were 107 038 cardiac surgical procedures between April 2002 and March 2012, conducted by 127 consultant surgeons and 190 consultant anaesthetists. MAIN OUTCOME MEASURE: Length of stay (LOS) up to 3 months postoperatively. RESULTS: The principal component of variation in outcomes was patient risk (represented by the EuroSCORE and remaining patient heterogeneity), accounting for 95.43% of the variation for postoperative LOS. The impact of the surgeon and centre was moderate (intra-class correlation coefficients ICC=2.79% and 1.59%, respectively), whereas the impact of the anaesthetist was negligible (ICC=0.19%). Similarly, 96.05% of the variation for prolonged LOS (>11 days) was attributable to the patient, with surgeon and centre less but still influential components (ICC=2.12% and 1.66%, respectively, 0.17% only for anaesthetists). Adjustment for year of operation resulted in minor reductions in variation attributable to surgeons (ICC=2.52% for LOS and 2.23% for prolonged LOS). CONCLUSIONS: Patient risk profile is the primary determinant of variation in LOS, and as a result, current initiatives to reduce hospital stay by modifying consultant performance are unlikely to have a substantial impact. Therefore, substantially reducing hospital stay requires shifting away from a one-size-fits-all approach to cardiac surgery, and seeking alternative treatment options personalised to high-risk patients.