CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Effect of Body Mass Index on Effectiveness of CT versus Invasive Coronary Angiography in Stable Chest Pain: The DISCHARGE Trial.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Is American Joint Replacement Registry Data Consistent With International Survivorship in Hip and Knee Arthroplasty? A Comparative Analysis.

BACKGROUND: In collaboration with the Orthopedic Data Evaluation Panel (ODEP), the American Joint Replacement Registry (AJRR) investigated the consistency of hip and knee arthroplasty survivorship results compared to the UK National Joint Registry (NJR). METHODS: A total of three primary knee devices and three primary hip devices were selected by AJRR and ODEP with known variation in performance. Implant manufacturers independently produced Kaplan Meier survivorship based on NJR data and submitted to ODEP for comparison. The AJRR mirrored the methodology, and results from both sources were stratified into three cohorts (all-age, < 65, and ≥ 65 years). RESULTS: There were 42,671 AJRR and 60,439 NJR primary knee cases and 70,169 AJRR and 422,657 NJR primary total hip arthroplasty cases. For TKA, performance between the AJRR and NJR were consistent, showing similar trends for comparatively high and low performing devices. Both PS and CR devices showed statistical agreement in survivorship for all 3 cohorts. Unicompartmental comparison also showed statistical agreement for the Medicare cohort. The all-age and < 65-year-old cohorts showed similar trends and reached statistical agreement through 7 and 6 years. For total hip arthroplasty, performance between the AJRR and NJR were consistent, showing similar trends for comparatively high and low performing devices; 0.18% average difference in survivorship at final follow-up (8 years). One femoral device did not reach statistical agreement but showed only 0.61% difference in survivorship. The remaining acetabular and femoral devices reached statistical agreement in all-ages and through 7 and 8 years in the ≥ 65-year-old cohort. CONCLUSIONS: AJRR and NJR performance trends and survivorship were similar across hip and knee arthroplasty with greatest consistency in the all-age and ≥ 65 cohorts. This focused comparison of survivorship showed encouraging results for reliability of patient outcomes in AJRR compared to the world's largest joint arthroplasty registry which has strong implications for global improvement in patient safety.

Antibiotic Laden Bone Cement Does Not Reduce Acute Periprosthetic Joint Infection Risk in Primary Total Knee Arthroplasty.

BACKGROUND: Periprosthetic joint infection (PJI) can be a serious complication of total knee arthroplasty (TKA). A method believed to decrease the incidence of PJI is antibiotic-laden bone cement (ALBC). Current clinical practice guidelines do not recommend ALBC in primary TKA. The purpose of this study was to compare ALBC to plain cement (PC) in preventing PJI in primary TKA. METHODS: This retrospective analysis included 109,242 Medicare patients in the American Joint Replacement Registry who underwent a cemented primary TKA from January 2017 to March 2021, and had at least 1 year of follow-up. Patients who received ALBC were compared to patients who received PC. Demographic and case-specific variables such as age, sex, race, body mass index, Charlson Comorbidity Index, anesthesia type, and operative time were used to create propensity scores. A logistic regression was run to predict the probability of receiving ALBC. Also, a multivariate model was run on the full unstratified population, using the same covariates as were used to create the propensity model. The primary outcome was differences in PJI rates. RESULTS: Logistic regression analysis showed that a higher preoperative diagnosis of osteoarthritis, higher Charlson Comorbidity Index, higher body mass index, women, race, and anesthesia requirements increased a patient's probability of receiving ALBC. In the full unstratified multivariate model, ALBC did not show a statistically significant difference in risk of revision for infection compared to PC. CONCLUSIONS: The use of ALBC in primary TKA has not been shown to be more efficacious in preventing PJI within the population of Medicare patients in the United States. However, this study is limited given it is a retrospective database study that may inherently have biases and the large dataset has a potential for overpowering the findings.

Impact of smoking in patients with suspected coronary artery disease in the randomised DISCHARGE trial.

OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.

Outcomes and Survivorships of Total Knee Arthroplasty Comparing Resurfaced and Unresurfaced Patellae.

BACKGROUND: The decision to resurface the patella in total knee arthroplasty (TKA) is controversial. While there is some consensus that leaving the patella unresurfaced increases risk of reoperation, there is conflicting evidence about patient reported outcomes or indications for resurfacing. This study sought to determine recent rates of patellar resurfacing, examine factors affecting rates of resurfacing, and analyze the associations between patellar resurfacing and both revision rates and patient-reported outcome measures (PROMs). METHODS: The American Joint Replacement Registry was used to identify primary TKAs performed for osteoarthritis between 2012 and 2021. Cases were classified as resurfaced patella and unresurfaced patella (URP). Outcomes analyzed included trends in patellar resurfacing, factors influencing rate of resurfacing, revision rates, operative time, and 2 PROMs. RESULTS: Rates of patellar resurfacing decreased and rates of URP increased significantly faster in ambulatory surgery centers and among high volume surgeons. Operative time was significantly lower in URP versus resurfaced patella (88.15 versus 89.90 minutes). The URP were significantly more likely to require revision surgery (odds ratio = 1.206 (1.078, 1.35), P = .0011). There was no significant difference in the likelihood of achieving the minimal clinically important difference in PROMs between resurfaced and nonresurfaced TKAs at 1 year (odds ratio = 1.060 (0.710, 1.581), P = .7755). CONCLUSION: There was no difference in minimal clinically important difference between resurfaced and URPs and no clinically relevant difference in operative time. However, URPs were more likely to require revision surgery. Therefore, the decision not to resurface should be made carefully considering the known risk of revision and the uncertain benefit.

Racial Disparities in Rates of Revision and use of Modern Features in Total Knee Arthroplasty, a National Registry Study.

BACKGROUND: The purpose of our study was to investigate the association of race and ethnicity with rates of modern implant use and postoperative outcomes in total knee arthroplasty (TKA) using the American Academy of Orthopaedic Surgeons American Joint Replacement Registry. METHODS: Adult TKAs from 2012 to 2020 were queried from the American Joint Replacement Registry. A total of 1,121,457 patients were available for analysis for surgical features and 1,068,210 patients for analysis of outcomes. Mixed-effects multivariable logistic regression models were used to examine the association of race with each individual surgical feature (unicompartmental knee arthroplasty (UKA) and robotic-assisted TKA (RA-TKA)) and 30- and 90-day readmission. A proportional subdistribution hazard model was used to model the risk of revision TKA. RESULTS: On multivariate analyses, compared to White patients, Black (odds ratio (OR): 0.52 P < .0001), Hispanic (OR 0.75 P < .001), and Native American (OR: 0.69 P = .0011) patients had lower rates of UKA, while only Black patients had lower rates of RA-TKA (OR = 0.76 P < .001). White (hazard ratio (HR) = 0.8, P < .001), Asian (HR = 0.51, P < .001), and Hispanic-White (HR = 0.73, P = .001) patients had a lower risk of revision TKA than Black patients. Asian patients had a lower revision risk than White (HR = 0.64, P < .001) and Hispanic-White (HR = 0.69, P = .011) patients. No significant differences existed between groups for 30- or 90-day readmissions. CONCLUSION: Black, Hispanic, and Native American patients had lower rates of UKA compared to White patients, while Black patients had lower rates of RA-TKA compared to White, Asian, and Hispanic patients. Black patients also had higher rates of revision TKA than other races.

Timing and Factors Associated With Revision for Infection After Primary Total Knee Arthroplasty Based on American Joint Replacement Registry Data.

BACKGROUND: Infection following total knee arthroplasty (TKA) remains a challenging clinical problem. Using American Joint Replacement Registry data, this study examined factors related to the incidence and timing of infection. METHODS: Primary TKAs performed from January 2012 through December 2018 among patients ≥65 years of age at surgery were queried from the American Joint Replacement Registry and merged with Medicare data to enhance capture of revisions for infection. Multivariate Cox regressions incorporating patient, surgical, and institutional factors were used to produce hazard ratios (HRs) associated with revision for infection and mortality after revision for infection. RESULTS: Among 525,887 TKAs, 2,821 (0.54%) were revised for infection. Men had an increased risk of revision for infection at all-time intervals (≤90 days, HR = 2.06, 95% CI: 1.75-2.43, P < .0001; >90 days to 1 year, HR = 1.90, 95% CI: 1.58-2.28, P < .0001; >1 year, HR = 1.57, 95% CI: 1.37-1.79, P < .0001). TKAs performed for osteoarthritis had an increased risk of revision for infection at ≤90 days (HR = 2.01, 95% CI: 1.45-2.78, P < .0001) but not at later times. Mortality was more likely among patients who had a Charlson Comorbidity Index (CCI) ≥ 5 compared to those who had a CCI ≤ 2 (HR = 3.21, 95% CI: 1.35-7.63, P = .008). Mortality was also more likely among older patients (HR = 1.61 for each decade, 95% CI: 1.04-2.49, P = .03). CONCLUSION: Based on primary TKAs performed in the United States, men were found to have a persistently higher risk of revision for infection, while a diagnosis of osteoarthritis was associated with a significantly higher risk only during the first 90 days after surgery.

Animal products in neurosurgery - navigating informed consent.

Informed consent is an ethical and legal requirement integral to modern surgical practice. Clinicians have a duty to consider, disclose and discuss risks and concerns relevant to an individual patient. With medical advances there are now a significant number of animal-derived products and adjuncts available for use in modern neurosurgical practice, which may be relevant when consenting patients for specific procedures if such products are used. This paper highlights commonly used products in neurosurgery that contain animal-derived constituents with the aim of facilitating an informed discussion between the neurosurgeon and patient. We have reviewed the commonly used products in the centres of the authors and their commercial equivalents. The product information is taken from the manufacturer's instructions or the Federal Drug Administration documents regarding the product. Animal products commonly available to neurosurgeons can be broadly categorised into haemostatic agents, dural substitutes, dural sealants and bone cements. Many products contain a variety of animal (or human) derived products. In order to ensure informed consent and shared decision making, it is important to establish any relevant patient beliefs or views regarding the use of animal-derived products. Given the wide availability and use of neurosurgical adjuncts containing human or animal derived products, coupled with the heterogeneity within ethnic, religious, and social groups, each patient must be approached individually to ensure patient-specific concerns are identified and alternatives offered when appropriate.

Exploring the prevalence, impact and experience of cardiac cachexia in patients with advanced heart failure and their caregivers: A sequential phased study.

BACKGROUND: Cardiac Cachexia is a wasting syndrome that has a significant impact on patient mortality and quality of life world-wide, although it is poorly understood in clinical practice. AIM: Identify the prevalence of cardiac cachexia in patients with advanced New York Heart Association (NYHA) functional class and explore its impact on patients and caregivers. DESIGN: An exploratory cross-sectional study. The sequential approach had two phases, with phase 1 including 200 patients with NYHA III-IV heart failure assessed for characteristics of cardiac cachexia. Phase 2 focussed on semi-structured interviews with eight cachectic patients and five caregivers to ascertain the impact of the syndrome. SETTING/PARTICIPANTS: Two healthcare trusts within the United Kingdom. RESULTS: Cardiac Cachexia was identified in 30 out of 200 participants, giving a prevalence rate of 15%. People with cachexia had a significantly reduced average weight and anthropometric measures (p < 0.05). Furthermore, individuals with cachexia experienced significantly more fatigue, had greater issues with diet and appetite, reduced physical wellbeing and overall reduced quality of life. C-reactive protein was significantly increased, whilst albumin and red blood cell count were significantly decreased in the cachectic group (p < 0.05). From qualitative data, four key themes were identified: (1) 'Changed relationship with food and eating', (2) 'Not me in the mirror', (3) 'Lack of understanding regarding cachexia' and (4) 'Uncertainty regarding the future'. CONCLUSIONS: Cardiac cachexia has a debilitating effect on patients and caregivers. Future work should focus on establishing a specific definition and clinical pathway to enhance patient and caregiver support.

Lower Rates of Ceramic Femoral Head Use in Non-White Patients in the United States, a National Registry Study.

BACKGROUND: The purpose of our study was to investigate the association of race and ethnicity with the use of the newest technology and postoperative outcomes in total hip arthroplasty (THA) using the American Academy of Orthopaedic Surgeons (AAOS) American Joint Replacement Registry (AJRR). METHODS: Adult THA procedures were queried from the AJRR from 2012 to 2020. A mixed-effects multivariate regression model was used to evaluate the association of race and ethnicity with the use of the newest technology (ceramic femoral head, dual-mobility implant, and robotic assist) at 30-day, and 90-day readmission. A proportional subdistribution hazard model was used to model a risk of revision THA. RESULTS: There were 85,188 THAs with complete data for an analysis of outcomes and 103,218 for an analysis of ceramic head usage. The median length of follow-up was 37.9 months (interquartile range [IQR] 21.6 to 56.3 months). In multivariate models, compared to White non-Hispanic patients, Black (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.69-0.92, P < .001), Hispanic (OR 0.76, CI 0.59-0.99, P = .037), Asian (OR 0.74, CI 0.55-1.00, P = .045), and Native American (OR 0.52, CI 0.30-0.87, P = .004) patients all had significantly lower rates of ceramic head use in THA. Compared to White non-Hispanic patients, Asian (hazard ratio [HR] 0.39, CI 0.18-0.86, P = .008) and Hispanic (HR 0.43, CI 0.19-0.98, P = .043) patients had significantly lower rates of revision. No differences in 30-day or 90-day readmission rates were seen. CONCLUSION: Black, Hispanic, Native American, and Asian patients had lower rates of ceramic head use in THA when compared to White patients. These differences did not translate into worse clinical outcomes on a short-term follow-up. In fact, Asian patients had lower revision rates compared to non-Hispanic White patients. Additional study is necessary to evaluate the long-term consequence of lower ceramic head use in non-White patients in the United States.

Clinical pre-test probability for obstructive coronary artery disease: insights from the European DISCHARGE pilot study.

OBJECTIVES: To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting. METHODS: Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA. RESULTS: In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001). CONCLUSIONS: Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed. TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.

Correction to: Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.

Pilot study of the multicentre DISCHARGE Trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

OBJECTIVE: To implement detailed EU cardiac computed tomography angiography (CCTA) quality criteria in the multicentre DISCHARGE trial (FP72007-2013, EC-GA 603266), we reviewed image quality and adherence to CCTA protocol and to the recommendations of invasive coronary angiography (ICA) in a pilot study. MATERIALS AND METHODS: From every clinical centre, imaging datasets of three patients per arm were assessed for adherence to the inclusion/exclusion criteria of the pilot study, predefined standards for the CCTA protocol and ICA recommendations, image quality and non-diagnostic (NDX) rate. These parameters were compared via multinomial regression and ANOVA. If a site did not reach the minimum quality level, additional datasets had to be sent before entering into the final accepted database (FADB). RESULTS: We analysed 226 cases (150 CCTA/76 ICA). The inclusion/exclusion criteria were not met by 6 of the 226 (2.7%) datasets. The predefined standard was not met by 13 of 76 ICA datasets (17.1%). This percentage decreased between the initial CCTA database and the FADB (multinomial regression, 53 of 70 vs 17 of 75 [76%] vs [23%]). The signal-to-noise ratio and contrast-to-noise ratio of the FADB did not improve significantly (ANOVA, p = 0.20; p = 0.09). The CTA NDX rate was reduced, but not significantly (initial CCTA database 15 of 70 [21.4%]) and FADB 9 of 75 [12%]; p = 0.13). CONCLUSION: We were able to increase conformity to the inclusion/exclusion criteria and CCTA protocol, improve image quality and decrease the CCTA NDX rate by implementing EU CCTA quality criteria and ICA recommendations. KEY POINTS: • Failure to meet protocol adherence in cardiac CTA was high in the pilot study (77.6%). • Image quality varies between sites and can be improved by feedback given by the core lab. • Conformance with new EU cardiac CT quality criteria might render cardiac CTA findings more consistent and comparable.

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

BACKGROUND: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. METHODS: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. RESULTS: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. CONCLUSIONS: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02400229.

Correction to: Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

An amendment to this paper has been published and can be accessed via the original article.

Clinician Perception of a Machine Learning-Based Early Warning System Designed to Predict Severe Sepsis and Septic Shock.

OBJECTIVE: To assess clinician perceptions of a machine learning-based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). DESIGN: Prospective observational study. SETTING: Tertiary teaching hospital in Philadelphia, PA. PATIENTS: Non-ICU admissions November-December 2016. INTERVENTIONS: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert's helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. MEASUREMENTS AND MAIN RESULTS: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient's risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. CONCLUSIONS: In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning-based sepsis alerts.

A Machine Learning Algorithm to Predict Severe Sepsis and Septic Shock: Development, Implementation, and Impact on Clinical Practice.

OBJECTIVES: Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes. DESIGN: Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. SETTING: Tertiary teaching hospital system in Philadelphia, PA. PATIENTS: All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184). INTERVENTIONS: A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. MEASUREMENT AND MAIN RESULT: Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic blood pressure less than 90 mm Hg. The algorithm demonstrated a sensitivity of 26% and specificity of 98%, with a positive predictive value of 29% and positive likelihood ratio of 13. The alert resulted in a small statistically significant increase in lactate testing and IV fluid administration. There was no significant difference in mortality, discharge disposition, or transfer to ICU, although there was a reduction in time-to-ICU transfer. CONCLUSIONS: Our machine learning algorithm can predict, with low sensitivity but high specificity, the impending occurrence of severe sepsis and septic shock. Algorithm-generated predictive alerts modestly impacted clinical measures. Next steps include describing clinical perception of this tool and optimizing algorithm design and delivery.

An exploration of the prevalence and experience of cardiac cachexia: protocol for a mixed methods cross-sectional study.

BACKGROUND: Cachexia is a complex and multifactorial syndrome defined as severe weight loss and muscle wasting which frequently goes unrecognised in clinical practice [1]. It is a debilitating syndrome, resulting in patients experiencing decreased quality of life and an increased risk of premature death; with cancer cachexia alone resulting in 2 million deaths per annum [2]. Most work in this field has focused on cancer cachexia, with cardiac cachexia being relatively understudied - despite its potential prevalence and impact in patients who have advanced heart failure. We report here the protocol for an exploratory study which will: 1. focus on determining the prevalence and clinical implications of cardiac cachexia within advanced heart failure patients; and 2. explore the experience of cachexia from patients' and caregivers' perspectives. METHODS: A mixed methods cross-sectional study. Phase 1: A purposive sample of 362 patients with moderate to severe heart failure from two Trusts within the United Kingdom will be assessed for known characteristics of cachexia (loss of weight, loss of muscle, muscle mass/strength, anorexia, fatigue and selected biomarkers), through basic measurements (i.e. mid-upper arm circumference) and use of three validated questionnaires; focusing on fatigue, quality of life and appetite. Phase 2: Qualitative semi-structured interviews with patients (n = 12) that meet criteria for cachexia, and their caregivers (n = 12), will explore their experience of this syndrome and its impact on daily life. Interviews will be digitally recorded and transcribed verbatim, prior to qualitative thematic and content analysis. Phase 3: Workshops with key stakeholders (patients, caregivers, healthcare professionals and policy makers) will be used to discuss study findings and identify practice implications to be tested in further research. DISCUSSION: Data collected as part of this study will allow the prevalence of cardiac cachexia in a group of patients with moderate to severe heart failure to be determined. It will also provide a unique insight into the implications and personal experience of cardiac cachexia for both patients and carers. It is hoped that robust quantitative data and rich qualitative perspectives will promote crucial clinical discussions on implications for practice, including targeted interventions to improve patients' quality of life where appropriate.