Positive Predictive Value of Computerized Tomography Coronary Angiography versus Computerized Tomography Fractional Flow Reserve in a Real-world Population.

Background: Computed Tomography coronary angiography and fractional flow reserve (CTCA and CT-FFR) are noninvasive diagnostic tools for the detection of flow-limiting coronary artery stenoses. Although their negative predictive values are well established, there is a concern that the high sensitivity of these tests may lead to overestimation of coronary artery disease (CAD) and unnecessary invasive coronary angiography (ICA). We compared the positive predictive value (PPV) of CT-FFR with computerized tomography coronary angiography (CTCA) against the gold standard of ICA in different real-world patient groups. Methods: A retrospective analysis of 477 patients referred for CTCA or CT-FFR for investigation of possible coronary ischemia. Patients were excluded if the image quality was poor or inconclusive. Patient-based PPV was calculated to detect or rule out significant CAD, defined as more than 70% stenosis on ICA. A sub-analysis of PPV by indication for the scan was also performed. Patients who underwent invasive nonhyperemic pressure wire measurements had their instant wave-free ratio or resting full-cycle ratio compared with their CT-FFR values. Results: In a patient-based analysis, the overall PPV was 59.3% for CTCA and 76.2% for CT-FFR. This increased to 81.0% and 86.7%, respectively, for patients with stable angina symptoms. In patients with atypical angina symptoms, CT-FFR considerably outperformed CTCA with a PPV of 61.3% vs. 37.5%. There was not a linear relationship between invasive pressure wire measurement and CT-FFR value (r = 0.23, P = 0.265). Conclusion: The PPV of CTCA and CT-FFR is lower in the real world than in previously published trials, partly due to the heterogeneity of indication for the scan. However, in patients with typical angina symptoms, both are reliable diagnostic tools to determine the presence of clinically significant coronary stenoses. CT-FFR significantly outperforms CTCA in patients with more atypical symptoms and the targeted use of CT-FFR in this group may help to avoid unnecessary invasive procedures.

Assessment of the comparative agreement between chest radiographs and CT scans in intensive care units.

PURPOSE: Chest radiographs in critically ill patients can be difficult to interpret due to technical and clinical factors. We sought to determine the agreement of chest radiographs and CT scans, and the inter-observer variation of chest radiograph interpretation, in intensive care units (ICUs). METHODS: Chest radiographs and corresponding thoracic computerised tomography (CT) scans (as reference standard) were collected from 45 ICU patients. All radiographs were analysed by 20 doctors (radiology consultants, radiology trainees, ICU consultants, ICU trainees) from 4 different centres, blinded to CT results. Specificity/sensitivity were determined for pleural effusion, lobar collapse and consolidation/atelectasis. Separately, Fleiss' kappa for multiple raters was used to determine inter-observer variation for chest radiographs. RESULTS: The median sensitivity and specificity of chest radiographs for detecting abnormalities seen on CTs scans were 43.2% and 85.9% respectively. Diagnostic sensitivity for pleural effusion was significantly higher among radiology consultants but no specialty/experience distinctions were observed for specificity. Median inter-observer kappa coefficient among assessors was 0.295 ("fair"). CONCLUSIONS: Chest radiographs commonly miss important radiological features in critically ill patients. Inter-observer agreement in chest radiograph interpretation is only "fair". Consultant radiologists are least likely to miss thoracic radiological abnormalities. The consequences of misdiagnosis by chest radiographs remain to be determined.

Impact on stable chest pain pathways of CT fractional flow reserve.

OBJECTIVES: To evaluate the impact of introducing CT fractional flow reserve (FFRCT) on stable chest pain pathways, concordance with National Institute for Health and Care Excellence (NICE) chest pain guidelines, resource usage and revascularisation of patients from a tertiary UK cardiac centre rapid access chest pain clinic (RACPC). METHODS: Single-centre before and after study comparing data from electronic records and Strategic Tracing Service of all RACPC patients attending between 1 July 2017 and 31 December 2017, and 1 August 2018 and 31 January 2019. RESULTS: Two hundred and sixty-eight and 287 patients (overall mean age 62 years, range 26-89 years, 48.3% male), were eligible for first-line CT coronary angiography (CTCA) pre-FFRCT and post-FFRCT, respectively. First-line CTCA use per NICE Guideline CG95 increased (50.6% pre-FFRCT vs 75.7% post-FFRCT, p<0.001). More patients reached pathway endpoint (revascularisation or assumed medical management) after one investigation (74.9% pre-FFRCT vs 84.9% post-FFRCT, p=0.005). There were fewer stress (22.8% pre-FFRCT vs 7.7% post-FFRCT, p<0.001) and rest (10.4% pre-FFRCT vs 4.2% post-FFRCT, p=0.007) myocardial perfusion scans and diagnostic-only angiograms (25.5% vs 13.7%, p<0.001). Despite fewer invasive procedures (29.3% pre-FFRCT vs 17.6% post-FFRCT, p=0.002), revascularisation rates remained similar (10.4% pre-FFRCT vs 8.8% post-FFRCT, p=0.561). Avoiding invasive investigations reduced inpatient admissions (39.0% pre-FFRCT vs 24.3% post-FFRCT, p<0.001). Time to revascularisation was unchanged (153.5 days pre-FFRCT vs 142.0 post-FFRCT, p=0.925). Unplanned hospital attendances, emergency admissions and adverse events were similar. CONCLUSIONS: FFRCT adoption was associated with greater compliance with NICE guidelines, reduced invasive diagnostic angiography, planned admissions and needing more than one test to reach a pathway endpoint.

Local interventions for the management of alveolar osteitis (dry socket).

BACKGROUND: Alveolar osteitis (dry socket) is a complication of dental extractions more often involving mandibular molar teeth. It is associated with severe pain developing 2 to 3 days postoperatively with or without halitosis, a socket that may be partially or totally devoid of a blood clot, and increased postoperative visits. This is an update of the Cochrane Review first published in 2012.  OBJECTIVES: To assess the effects of local interventions used for the prevention and treatment of alveolar osteitis (dry socket) following tooth extraction. SEARCH METHODS: An Information Specialist searched four bibliographic databases up to 28 September 2021 and used additional search methods to identify published, unpublished, and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials of adults over 18 years of age who were having permanent teeth extracted or who had developed dry socket postextraction. We included studies with any type of local intervention used for the prevention or treatment of dry socket, compared to a different local intervention, placebo or no treatment. We excluded studies reporting on systemic use of antibiotics or the use of surgical techniques because these interventions are evaluated in separate Cochrane Reviews. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We followed Cochrane statistical guidelines and reported dichotomous outcomes as risk ratios (RR) and calculated 95% confidence intervals (CI) using random-effects models. For some of the split-mouth studies with sparse data, it was not possible to calculate RR so we calculated the exact odds ratio (OR) instead. We used GRADE to assess the certainty of the body of evidence. MAIN RESULTS: We included 49 trials with 6771 participants; 39 trials (with 6219 participants) investigated prevention of dry socket and 10 studies (with 552 participants) looked at the treatment of dry socket. 16 studies were at high risk of bias, 30 studies at unclear risk of bias, and 3 studies at low risk of bias. Chlorhexidine in the prevention of dry socket When compared to placebo, rinsing with chlorhexidine mouthrinses (0.12% and 0.2% concentrations) both before and 24 hours after extraction(s) substantially reduced the risk of developing dry socket with an OR of 0.38 (95% CI 0.25 to 0.58; P < 0.00001; 6 trials, 1547 participants; moderate-certainty evidence). The prevalence of dry socket varies from 1% to 5% in routine dental extractions to upwards of 30% in surgically extracted third molars. The number of patients needed to be treated (NNT) with chlorhexidine rinse to prevent one patient having dry socket was 162 (95% CI 155 to 240), 33 (95% CI 27 to 49), and 7 (95% CI 5 to 10) for control prevalence of dry socket 0.01, 0.05, and 0.30 respectively.  Compared to placebo, placing chlorhexidine gel intrasocket after extractions reduced the odds of developing a dry socket by 58% with an OR of 0.44 (95% CI 0.27 to 0.71; P = 0.0008; 7 trials, 753 participants; moderate-certainty evidence). The NNT with chlorhexidine gel (0.2%) to prevent one patient developing dry socket was 180 (95% CI 137 to 347), 37 (95% CI 28 to 72), and 7 (95% CI 5 to 15) for control prevalence of dry socket of 0.01, 0.05, and 0.30 respectively. Compared to chlorhexidine rinse (0.12%), placing chlorhexidine gel (0.2%) intrasocket after extractions was not superior in reducing the risk of dry socket (RR 0.74, 95% CI 0.46 to 1.20; P = 0.22; 2 trials, 383 participants; low-certainty evidence).  The present review found some evidence for the association of minor adverse reactions with use of 0.12%, 0.2% chlorhexidine mouthrinses (alteration in taste, staining of teeth, stomatitis) though most studies were not designed explicitly to detect the presence of hypersensitivity reactions to mouthwash as part of the study protocol. No adverse events were reported in relation to the use of 0.2% chlorhexidine gel placed directly into a socket. Platelet rich plasma in the prevention of dry socket  Compared to placebo, placing platelet rich plasma after extractions was not superior in reducing the risk of having a dry socket (RR 0.51, 95% CI 0.19 to 1.33; P = 0.17; 2 studies, 127 participants; very low-certainty evidence).  A further 21 intrasocket interventions to prevent dry socket were each evaluated in single studies, and there is insufficient evidence to determine their effects. Zinc oxide eugenol versus Alvogyl in the treatment of dry socket Two studies, with 80 participants, showed that Alvogyl (old formulation) is more effective than zinc oxide eugenol at reducing pain at day 7 (mean difference (MD) -1.40, 95% CI -1.75 to -1.04; P < 0.00001; 2 studies, 80 participants; very low-certainty evidence) A further nine interventions for the treatment of dry socket were evaluated in single studies, providing insufficient evidence to determine their effects. AUTHORS' CONCLUSIONS: Tooth extractions are generally undertaken by dentists for a variety of reasons, however, all but five studies included in the present review included participants undergoing extraction of third molars, most of which were undertaken by oral surgeons. There is moderate-certainty evidence that rinsing with chlorhexidine (0.12% and 0.2%) or placing chlorhexidine gel (0.2%) in the sockets of extracted teeth, probably results in a reduction in dry socket. There was insufficient evidence to determine the effects of the other 21 preventative interventions each evaluated in single studies. There was limited evidence of very low certainty that Alvogyl (old formulation) may reduce pain at day 7 in patients with dry socket when compared to zinc oxide eugenol.

Quantitative Ultrasound of the Mandible as a Novel Screening Approach for Osteoporosis.

This study used an axial transmission quantitative ultrasound (QUS) device to assess mandibular bone strength. The aim of the study was first to establish the precision and repeatability of the axial transmission QUS measurement for a range of mandibular anatomic sites, and second to investigate the ability of the modality to differentiate between osteoporotic subjects and a control group. Three groups of adult Caucasian women were recruited: (1) healthy premenopausal women (n = 26), (2) healthy postmenopausal women (n = 48), and (3) women with osteoporosis (n = 53). Subjects were excluded from groups 1 and 2 if they had any pre-existing bone conditions. Speed of sound (SOS) measurements were taken from the mandible using an OmniSense multisite QUS device. Group 3 had dual-energy X-ray absorptiometry scans of the lumbar spine and femur. The most suitable site on the mandible was determined by repeat SOS measurements in 10 healthy premenopausal subjects, at 5 different sites. The parasymphysis site had the lowest root mean squared coefficient of variation at 0.74%, and was chosen as the most suitable site for mandibular SOS measurements. Group 1 and group 2 had significantly higher mean SOS measurements than the osteoporotic subjects (group 3), with means of 3683 m/s (210), 3514 m/s (221), and 3312 m/s (264), respectively. A 1-way analysis of variance confirmed a statistically significant difference between mean SOS measurements from the 3 groups (p < 0.0001). Axial transmission QUS of the mandible can differentiate between subjects with osteoporosis and a healthy control group, and shows potential for use as a screening tool for osteoporosis.

Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study.

OBJECTIVE: To assess whether hereditary myopathy with early respiratory failure (HMERF) due to the c.951434T>C; (p.Cys31712Arg) TTN missense mutation also includes a cardiac phenotype. METHOD: Clinical cohort study of our HMERF cohort using ECG, 2D echocardiogram, and cross-sectional cardiac imaging with MRI or CT. RESULTS: We studied 22 participants with the c.951434T>C; (p.Cys31712Arg) TTN missense mutation. Three were deceased. Cardiac conduction abnormalities were identified in 7/22 (32%): sustained atrioventricular tachycardia (n = 2), atrial fibrillation (n = 2), nonsustained atrial tachycardia (n = 1), premature supraventricular complexes (n = 1), and unexplained sinus bradycardia (n = 1). In addition, 4/22 (18%) had imaging evidence of otherwise unexplained cardiomyopathy. These findings are supported by histopathologic correlation suggestive of myocardial cytoskeletal remodeling. CONCLUSIONS: Coexisting cardiac and skeletal muscle involvement is not uncommon in patients with HMERF arising due to the c.951434T>C; (p.Cys31712Arg) TTN mutation. All patients with pathogenic or putative pathogenic TTN mutations should be offered periodic cardiac surveillance.

Oral Squamous Cell Carcinoma Presenting in a Patient Receiving Adalimumab for Rheumatoid Arthritis.

The efficacy of biologic agents in the treatment of inflammatory immune-mediated conditions has been clearly shown, but there also are numerous reports of adverse effects. Most reported adverse effects have been associated with tumor necrosis factor-α (TNF-α) inhibitors and include a possible increased risk of malignancy. There have been some reported cases of oral cancer developing in patients treated with TNF-α inhibitors. This case report describes a patient who was taking adalimumab for rheumatoid arthritis and who presented with a squamous cell carcinoma (SCC) in the mandible. Diagnosis was complicated because the clinical appearance was of a nonhealing extraction socket and the patient had a history of bisphosphonate therapy. An initial diagnosis of bisphosphonate-related osteonecrosis of the jaws was made, which delayed the commencement of appropriate treatment. This case highlights the importance of ruling out SCC in patients taking biological agents with unusual symptoms.