Heart and Vessels

Coronary computed tomography angiography as a tool for long-term cardiovascular risk stratification in diabetic patients Abstract Objectives of the study were to examine the long-term prognostic power of coronary computed tomography angiography (CCTA) to predict death or myocardial infarction in patients with diabetes mellitus (DM). The prognostic value of CCTA in diabetic patients has been confirmed for short- and intermediate follow-up durations. The slowly progressing nature of coronary artery disease (CAD), however, underlines the necessity to validate CCTA for longer observation periods in this high-risk population. A total of 132 patients with DM and 1781 without DM were examined by CCTA and followed for a median duration of 9.7 (IQR 6.9, 11.2) and 9.9 (IQR 6.9, 11.1) years, respectively. Cox proportional hazards analysis was used for the composite endpoint of death and myocardial infarction. Warranty period was defined as the number of years that an individual stays in a low-risk group with a cumulative probability for the endpoint below 1% and calculated for patients with/without DM and rising degrees of CAD. The study endpoint was reached in 12 (9.1%) patients with and 87 (4.9%) patients without DM (p = 0.024). Quantification of coronary stenosis by CADRADS or CAD severity (normal/non-obstructive/obstructive) was incremental for endpoint prediction with a multivariate (+Morise) χ2 of 3.90 and 3.85, respectively. The lowest annual event rate of 0.19% was noted in non-diabetic patients with no CAD, translating to a warranty period of 5.26 years. The highest annual event rate of 1.73% was found in diabetic patients with obstructive CAD, corresponding to a warranty period of 0.58 years. Compared to patients with no DM and no CAD, the risk of death or myocardial infarction in diabetic patients increased with rising levels of coronary obstruction at multivariate hazard ratios (HR) of 3.28 [95% CI 2.32, 4.64 (p < 0.001)], 3.02 [95% CI 2.19, 4.17 (p < 0.001)] and 9.40 [95% CI 4.90, 18.03 (p < 0.001)] for normal coronary arteries, non-obstructive CAD and obstructive CAD. This study validates the long-term prognostic utility of CCTA-assessed CAD for predicting death or myocardial infarction in a population of patients with DM. The rates of death or myocardial infarction rise with CAD severity in diabetic and non-diabetic patients, identifying the highest risk group of patients with DM and obstructive CAD.

Plaque modification and stabilization after paclitaxel-coated balloon treatment for de novo coronary lesions Abstract This study aimed to assess the healing response, as evidenced through temporal morphological and functional changes, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions. This retrospective, observational study, included patients with significant de novo coronary lesions who were treated with PCB and had serial angiographic, intravascular ultrasound virtual histology (IVUS-VH), fractional flow reserve (FFR) measurements, and optical coherence tomography (OCT) performed before balloon angioplasty (BA), after BA, and at 9-month follow-up. A total of 20 patients (21 lesions) were included in this study. After PCB treatment, IVUS showed significant increases in the mean vessel area (12.0 ± 2.2 mm2 to 13.8 ± 2.5 mm2, p = 0.023), and mean lumen area (5.6 ± 1.2 mm2 to 7.0 ± 1.5 mm2, p = 0.003). Coronary flow was restored after BA with an FFR value of 0.87 ± 0.04 which was sustained at 9-month follow-up with no significant decrease (0.83 ± 0.08, p = 0.329). Serial OCT analysis showed that at 9-month follow-up dissections after BA sealed in 14 lesions (67%), whilst the macrophages decreased from 10 (50%) to 7 (35%) lesions, and the cap thickness of plaque increased from 0.12 ± 0.06 mm to 0.17 ± 0.09 mm (p = 0.007). PCB treatment for de novo coronary lesions showed persistent anatomical and functional patency at mid-term follow-up. Plaque modification, vascular remodeling, and plaque stabilization were also observed during follow-up.

U-shaped association of central pulse pressure with long-term prognosis after ST-segment elevation myocardial infarction Abstract The relationship between central pulse pressure (CPP) measured at the time of primary percutaneous coronary intervention (PPCI) and long-term prognosis after ST-segment elevation myocardial infarction (STEMI) has not been investigated. CPP measurements were performed in 1348 patients with STEMI (327 women; mean age 62.5 ± 12.1 years) undergoing PPCI. Aortic systolic and diastolic blood pressure was measured before intervention. The primary outcome was 8-year all-cause mortality. The median [25–75th percentile] CPP value was 55.0 [43.0–70.0] mmHg. CPP correlated negatively with heart rate (P < 0.001), body mass index (P = 0.007), Killip class (P < 0.001) and initial area at risk (P < 0.001) and positively with age (P < 0.001), female sex (P < 0.001), diabetes (P = 0.012), arterial hypertension (P < 0.001) and glomerular filtration rate (P = 0.004). There were 181 deaths over the follow-up. In patients with CPP within the 1st, 2nd and 3rd tertiles, the Kaplan–Meier estimates of mortality were 17.3%, 10.8% and 24.2%, respectively; univariable hazard ratio [HR] =1.52, 95% confidence interval [CI] 0.99 to 2.32; P = 0.055 for tertile 1 vs. tertile 2 and HR =2.09 [1.36–3.21]; P < 0.001 for tertile 3 vs. tertile 2. For CPP values lower than 35 mmHg and higher than 71 mmHg, the association between CPP and all-cause mortality was significant (HR =1.276 [1.004–1.621] for the 35 mmHg value and HR =1.289 [1.003–1.657] for the 71 mmHg value) compared with the CPP reference value (54 mmHg). After adjustment, the association between CPP and all-cause mortality was attenuated (P = 0.304). In patients with STEMI undergoing PPCI there is a U-shaped association between CPP and mortality up to 8 years after PPCI.

Influence of chronic kidney disease on coronary plaque components in coronary artery disease patients with both diabetes mellitus and hypertension Abstract Chronic kidney disease (CKD) is well known to be associated with an increased incidence of coronary artery disease (CAD). Diabetes mellitus (DM) and hypertension (HTN), both of which are traditional risk factors for CAD, are the two most common causes of CKD. However, the influence of CKD on coronary atherosclerosis in CAD patients who have both DM and HTN remains uncertain. In these patients, we examined the relationship between CKD and coronary plaque using integrated backscatter intravascular ultrasound (IB IVUS). Two hundred two CAD patients with both DM and HTN who underwent percutaneous coronary intervention using IB IVUS were included. The patients were divided into two groups: CKD group (n = 106) and non-CKD group (n = 96). Gray-scale and IB IVUS examinations were conducted for the non-culprit segment of a coronary artery. As a result, although there was no significant difference in the percentage of plaque volume, the percentage of lipid volume was significantly higher in the CKD group than in the non-CKD group [median (IQR): 56.7% (45.4–67.0%) vs. 52.0% (38.3–60.2%), p = 0.03]. In all of the patients, estimated glomerular filtration rate levels were negatively correlated with the percentage of lipid volume (r = − 0.15, p = 0.03) and positively correlated with the percentage of fibrosis volume (r = 0.15, p = 0.04). A multivariate regression analysis showed that CKD was an independent predictor associated with the increased lipid volume (β = 0.15, p = 0.047) and decreased fibrosis volume (β = − 0.16, p = 0.03) in coronary plaques. In conclusion, among CAD patients who had both DM and HTN, CKD was associated with lipid-rich coronary plaques. CKD may contribute to the vulnerability of coronary plaque in these very high-risk patients.

Effective blood hemoglobin level to predict prognosis in heart failure with preserved left ventricular ejection fraction: results of the Japanese heart failure syndrome with preserved ejection fraction registry Abstract High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan–Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4 g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.

Relationship between electrical conduction and phasic left atrial function: P-wave signal-averaged electrocardiography and time-left atrial volume curve assessments using two-dimensional speckle-tracking echocardiography Abstract P-wave signal-averaged electrocardiography (P-SAECG) can detect imperceptible conduction abnormalities, and volume analysis using two-dimensional speckle-tracking echocardiography (2-DSTE) allows us to easily measure the phasic function of the left atrium (LA). Both conduction abnormalities and functional deformation of the LA may be linked to the clinical outcome; however, the exact relationship is unclear. The aim of this study was to investigate the relationship between the phasic function of the LA and electrical conduction using P-SAECG and 2-DSTE. The subjects were 112 male volunteers (age 46.9 ± 13.2 years) with normal cardiac function who underwent P-SAECG and 2-DSTE. The filtered p-wave duration (FPD) and the root-mean-square voltage for the last 20 ms (RMS20) on P-SAECG wave were measured in ms and μV, respectively. Total emptying function (EF) (reservoir function), passive EF (conduit function), and active EF (booster pump function) of the LA were calculated as percentages to evaluate phasic LA function using 2DSTE. The mean FPD was 134.3 ± 11.7 ms and the mean RMS20 was 4.59 ± 2.39 μV. The mean total EF was 60.5 ± 13.1%, mean passive EF was 39.4 ± 13.9%, and mean active EF was 35.1 ± 13.9%. FPD had a negative correlation with passive EF (r = − 0.20, p = 0.039). FPD showed no significant relationship with total EF (r = − 0.03, p = 0.78) or active EF (r = 0.13, p = 0.18). There was a significant association between RMS20 and passive EF (r = 0.19, p = 0.048); however, no there was no correlation between RMS20 and total EF (r = 0.12, p = 0.23), or between RMS20 and passive EF (r = − 0.02, p = 0.86). In multivariate regression analysis, passive EF was an independent factor that influenced FPD duration. This study indicated that FPD was associated with conduit function, which includes phasic LA function. Therefore, electrical conduction of the LA and left ventricular diastolic function are closely related. In the clinical setting, when conduction abnormalities are detected, lifestyle measures or interventions can be applied to reduce cardiovascular risk.

Can we rely on Danish? Real-world data on patients with nonischemic cardiomyopathy from the German Device Registry Abstract According to current guidelines prophylactic implantable cardioverter-defibrillator (ICD) therapy is recommended in patients with significantly impaired left ventricular systolic function. However, the recently published DANISH trial did not find a significantly lower long-term rate of death from any cause compared with usual clinical care in patients with non-ischemic cardiomyopathy. We investigated whether registry data from a multi-center 'real-life' registry on patients with non-ischemic cardiomyopathy are similar to this trial. The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5451 patients receiving device implantations in 50 German centers. The present analysis of DEVICE focused on patients with non-ischemic cardiomyopathy and a left ventricular ejection fraction ≤35% who received a prophylactic ICD. Out of 779 patients with symptomatic heart failure and nonischemic cardiomyopathy, 33.1% received a single chamber ICD (VVI), while 11.0% were implanted with a dual-chamber ICD (DDD), and 55.8% received a defibrillator system for cardiac resynchronization therapy. Median follow-up was 16.1 months. 90.7% were alive at follow-up, 9.3% had died during this period. Overall mortality after one year was 5.4%. Overall mortality one year after implantation was significantly increased in patients 68 years and older(7.9%) as compared to younger patients (59–68 years: 2.5%; < 59 years: 3.8%; p < 0.015). Data from the present registry support the recently published results of the DANISH trial. In particular the influence of an increased age as proven in the DANISH trial might also play a role in the present collective. This limits the potential beneficial effect of ICD therapy in particular in the elderly population.

Validation of wearable textile electrodes for ECG monitoring Abstract A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.

Prognostic value of echocardiographic parameters for right ventricular function in patients with acute non-massive pulmonary embolism Abstract A prognostic value of right ventricular (RV) systolic function assessed by echocardiography in patients with acute non-massive pulmonary embolism (PE) remains controversial. The hypothesis was RV free wall strain measured using speckle-tracking echocardiography might be a powerful prognostic factor in those patients. We aimed to evaluate the prognostic value of echocardiographic measurements of RV systolic function for clinical outcomes and to assess the correlation between the echocardiographic RV function parameters in patients with acute non-massive PE. Between November 2013 and September 2016, 144 consecutive patients diagnosed as acute non-massive pulmonary embolism were prospectively enrolled and echocardiographic evaluations were performed within 1 week of diagnosis to measure various parameters of RV systolic function. The primary endpoint was in-hospital events, the composite of in-hospital PE-related death, need of additive treatments such as thrombolysis or pulmonary artery thromboembolectomy, and need of inotropics due to unstable vital sign. Among patients (mean age 60.3 ± 14.7 years, 50% female) with acute non-massive PE, the in-hospital event rate was 11.1% (16 of 144 patients). In multivariate logistic regression analysis, after adjustment of confounding factors such as age, gender, and diabetes mellitus, RV free wall strain [odd ratio (OR) 1.12, 95% confidence interval (CI) 1.04–1.21, p = 0.002] and RV global wall strain (OR 1.20, 95% CI 1.07–1.35, p = 0.002) were independent predictors for in-hospital events. The event rates were significantly different between groups classified based on RV free wall strain with cut-off value of − 15.85% (p < 0.001). RV strain assessed with speckle-tracking echocardiography is an independent prognostic marker for in-hospital events in patients with acute non-massive PE. Our results may help identify high–intermediate risk patients who need a closer monitoring.

Direct comparison of prognostic ability of cardiac biomarkers for cardiogenic stroke and clinical outcome in patients with stroke Abstract Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Ear, Nose & Throat

Unethical Surgery Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 186-187, April-May 2019.

Intratympanic Membrane Congenital Cholesteatoma Removal Using an Endoscopic System: A Case Report Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 188-189, April-May 2019.

Endoscopic Finding of a Dentigerous Cyst Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 190-191, April-May 2019.

Laryngeal Manifestation of Intranasal Acetaminophen Abuse and Review of Literature Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 192-194, April-May 2019.

Hemorrhagic Thyroid Nodule Resulting in Expanding Neck Hematoma Following Blunt Cervical Trauma Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 195-196, April-May 2019.

Aggressive Necrotizing Fasciitis of the Head and Neck Resulting in Massive Defects Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 197-200, April-May 2019.

An Unusual Fungal Infection in the Masticator Space With Intracranial Extension in an Immunocompromised Patient Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 201-202, April-May 2019.

An Incidental Mass on CT in an Otherwise Asymptomatic Patient With Heat Stroke Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 203-204, April-May 2019.

Encapsulated Sinonasal Schwannoma Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 205-206, April-May 2019.

Long-Term Effectiveness of Balloon Catheter Sinuplasty in Pediatric Chronic Maxillary Sinusitis Ear, Nose & Throat Journal, Volume 98, Issue 4, Page 207-211, April-May 2019.  The objective of our study was to assess the long-term effectiveness of balloon catheter sinuplasty in the treatment of pediatric chronic maxillary sinusitis following failed first-line medical and surgical management with adenoidectomy. Pediatric patients younger than 12 years were reviewed for having failed previous adenoidectomy and undergone a balloon catheter sinuplasty between August 2006 and March 2011 for chronic rhinosinusitis. Demographic data and clinical characteristics were recorded in patients who met inclusion criteria. Outcomes were assessed by need for functional endoscopic sinus surgery and persistence of chronic infection within at least 5 years of follow-up. Failure was defined by any child who was rediagnosed with chronic sinus disease after balloon catheter sinuplasty or who required endoscopic sinus surgery within 5 years. Sixty-two children were reviewed, with 38 patients meeting inclusion criteria (prior adenoidectomy, a preoperative Lund-Mackay score of ≥5, and balloon catheter sinuplasty). The mean age (standard deviation) was 6.76 (2.27) years with an age range of 2 to 11 years. Eight children (21.1%, P < .01) continued to have chronic sinus complaints following balloon procedure, with 5 (13.1%) individuals requiring eventual endoscopic surgery within 5 years. Age, asthma, allergy, and gender did not have any statistically significant impact on outcome. Balloon catheter sinuplasty is an effective long-term alternative for the treatment of chronic rhinosinusitis in pediatric patients, hoping to avoid further infections and eventual endoscopic surgery. Baseline Low Prognostic Nutritional Index Predicts Poor Survival in Locally Advanced Nasopharyngeal Carcinomas Treated With Radical Concurrent Chemoradiotherapy Ear, Nose & Throat Journal, Ahead of Print.  Background:To retrospectively assess the impact of prognostic nutritional index (PNI) on survival outcomes of patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with concurrent chemoradiotherapy (CCRT).Methods:This study incorporated 154 patients with LA-NPC who received exclusive cisplatinum-based CCRT. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of pretreatment PNI cutoffs influencing survival results. The primary end point was the interaction between the overall survival (OS) and PNI values, while cancer-specific survival (CSS) locoregional progression-free survival (LR-PFS), distant metastasis–free survival (DMFS), and PFS were the secondary end points.Results:A rounded PNI cutoff value of 51 was identified in ROC curve analyses to exhibit significant link with CSS, OS, DMFS, and PFS outcomes, but not LR-PFS. Patients grouping per PNI value (≥51 [N = 95] vs <51 [N = 49]) revealed that PNI < 51 group had significantly shorter median CSS (P < .001), OS (P < .001), DMFS (P < .001), and PFS (P < .001) times than the PNI ≥ 51 group, and the multivariate results confirmed the PNI < 51 as an independent predictor of poor outcomes for each end point (P < .05 for each). The unfavorable impact of the low PNI was also continued at 10-year time point with survival rates of 77.9% versus 42.4%, 73.6% versus 33.9%, 57.9% versus 27.1%, and 52.6% versus 23.7% for CSS, OS, DMFS, and PFS, respectively. Additionally, we found that PNI < 51 was significantly associated with higher rates of weight loss >5% over past 6 months (49.2% versus 11.6%; P = .002) compared to PNI < 51 group.Conclusion:Low pre-CCRT PNI levels were independently associated with significantly reduced CSS, OS, DMFS, and PFS outcomes in patients with LA-NPC treated with definitive CCRT. Rare Earth Metal Magnets: An Unusual Airway Foreign Body Ear, Nose & Throat Journal, Ahead of Print.  Nasal Polyps and Chronic Obstructive Pulmonary Disease—An Oft Overlooked Association Ear, Nose & Throat Journal, Ahead of Print.  Accidental Intubation of the Soft Palate Ear, Nose & Throat Journal, Ahead of Print.  Head and Neck Cancer Complications in the Geriatric Population Based on Hospital Case Volume Ear, Nose & Throat Journal, Ahead of Print.  Objective:To determine whether surgical case volume is a predictive factor of surgical outcomes when managing geriatric patients with head andneck cancer.Methods:A cross-sectional study design was used. Data were obtainedfrom the Vizient Database, which included a total of 93 academicinstitutions. Men and women aged between 65 and 100 years undergoing head and neck cancer surgery during 2009 and 2012,excluding cases of thyroid cancer and skin cancer of the head and neck(n = 4544) were included in the study. Hospital case volume was definedas low (≤21 cases/year), moderate (22-49 cases/year), or high (≥50 cases/year). The frequency of comorbidities and complications wasmeasured by hospital case volume using a χ2 test. Significancewas determined with an α level of .05.Results:The largest number of head and neck cancer cases involving comorbidities (90.54%) and the highest rate of overall complications(27.50%) occurred in moderate case volume institutions compared to athe complication rate of 22.89% in low volume hospitals and 21.50% in highvolume hospitals (P < .0001). The most common comorbidities across all3 hospital case volumes included hypertension, metastatic cancer,and chronic pulmonary disease and the most common complicationsincluded hemorrhage/hematoma and postoperative pulmonarycompromise.Conclusion:With more geriatric patients requiring surgery for head andneck cancer, it would be beneficial to manage the more complex cases at high volume centers and to develop multidisciplinary teams to optimizecase management and minimize complications. Traumatic Orbital Subperiosteal Hematoma With Acute Visual Compromise: Role of the Head and Neck Surgeon Ear, Nose & Throat Journal, Ahead of Print.  The primary goal was to report our institutional experience of a rare, vision-threatening complication following craniomaxillofacial trauma. A retrospective review was performed between January 2016 and January 2018 to identify 3 patients with traumatic orbital subperiosteal hematoma (OSPH). Visual acuity, intraocular pressures (IOPs), and the need for surgical intervention were abstracted. The age range was 36 to 88 years. Indications for surgical intervention include relative afferent pupillary defect, gaze restriction, visual impairment, and elevated IOP. Preoperatively, IOP range was 15.0 to 25.0. Two patients required OSPH evacuation via a medial brow approach. Follow-up after ocular injury ranged from 25 to 41 days, with IOP range of 13.0 to 16.0. Traumatic OSPH is an uncommon clinical finding; prompt assessment with consideration of surgical intervention may mitigate deleterious long-term morbidity, chiefly sudden blindness. Further research efforts may elucidate the optimal method in the management of this complex clinical entity. The Creation of a Sustainable Otolaryngology Department in Malawi Ear, Nose & Throat Journal, Ahead of Print.  There is a significant lack of surgeons in the developing world. Malawi Africa is one of the poorest and medically underserved countries in the World, with surgical care particularly lacking. Providing surgical services has numerous barriers, such as availability of well-trained surgeons, infrastructure, continuity of care, and access to care. There is currently one otolaryngologist in Malawi who provides complete access to this subspecialty. The development of the otolaryngology department was successful through institutional, local, national, and international collaboration, with a long-term goal of sustainability. An established department can train the next generation of surgeons for the preservation and growth of the surgical workforce. Once the department approaches independence, the role of outside collaboration transforms primarily from financial to a bi-directional partnership encompassing education, training, and leadership. Extranodal NK/T-Cell Lymphoma, Nasal Type—Case Report of 2 Cases Ear, Nose & Throat Journal, Ahead of Print.  Predictive Factors for Perinatal Outcomes of Infants Diagnosed With Micrognathia Antenatally Ear, Nose & Throat Journal, Ahead of Print.  Introduction:Advances in fetal imaging have allowed us to identify abnormalities previously not appreciated. With this study, we hope to identify factors predicting a difficult airway at birth and review the perinatal outcomes of these patients.Methods:Sixteen patients with antenatally diagnosed micrognathia were reviewed from a tertiary care hospital database from 2011 to 2016. Jaw index (JI), amniotic fluid index (AFI), glossoptosis, gastric size, and oropharynx obliteration were assessed. The airway support required at birth, specialist team involvement, and outcomes were evaluated.Results:Nine (56.3%) of 16 patients had JI <5th percentile, 3 (33.3%) of 9 had difficult intubation, 2 (22.2%) of 9 needed an emergency tracheostomy, and 1 (11.1%) of 9 died. Seven patients had polyhydramnios, 2 (28.6%) of 7 had difficult intubation, 2 (28.6%) of 7 required tracheostomy, and 1 (14.3%) of 7 died. Twelve patients had either JI <5th percentile or abnormal AFI, 5 (41.7%) of 12 had difficult intubation, 2 (16.7%) of 12 required tracheostomy, and 1 (8.33%) of 12 died. For the group without otolaryngology consultation, 8 (50%) of 16, 1 (12.5%) of 8 had difficult intubation and 1 (12.5%) of 8 died because airway was not secured after 45 minutes of resuscitation.Conclusion:Jaw index <5th percentile or abnormal AFI predicts a difficult airway. A multidisciplinary approach with otolaryngology involvement for airway intervention may be required at birth. Expression Profile of Survivin and p16 in Laryngeal Squamous Cell Carcinoma: Contribution of Tunisian Patients Ear, Nose & Throat Journal, Ahead of Print.  The objective of this study was to evaluate the expression of survivin and p16 in laryngeal squamous cell carcinoma (LSCC) in order to analyze their pathogenesis and prognostic significance in Tunisian patients. A total of 70 patients with LSCC collected at the Salah Azaiez Cancer Institute of Tunis were retrospectively evaluated. Expression of survivin and p16 was examined using immunohistochemistry, and the correlations with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS) were statistically evaluated. The positive expression of survivin and p16 were found in 58.6% and 51.43% of LSCC cases, respectively. The p16 expression was not associated with either clinical parameters or patient survival, whereas there was a strong correlation of survivin expression and lymph node metastases (P = .002), alcohol consumption (P = .024), and therapeutic protocol (with or without chemotherapy; P = .001). Kaplan-Meier survival curves showed that patients with LSCC having positive survivin expression have shorter OS (P = .026) and shorter DFS (P = .01) than those with negative expression. Positive survivin expression was also correlated with high recurrence rate (P = .014). Therefore, survivin is a poor prognostic marker for LSCC but the therapeutic protocol remains, in multivariate study, the most decisive for the OS and DFS of our patients with P < .01. Our data indicated that, in Tunisian laryngeal squamous cell carcinoma, survivin expression is associated with unfavorable outcomes and represents a predictor marker of recurrence and chemoresistance. However, p16 expression has no prognosis value.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Occupational and Environmental Health

Blue–yellow dyschromatopsia in toluene-exposed workers Abstract Purpose To evaluate the effects of a chronic occupational exposure to toluene on color vision. Methods Color vision was tested in 51 workers exposed to pure toluene and in 51 matched control subjects. Current exposure was determined by biological monitoring. Blood samples were taken at the end of a Friday shift. Color vision ability was assessed using the Ishihara plates (to screen for congenital dyschromatopsia), the Farnsworth panel D-15 test, the Lanthony panel D-15 desaturated test, the Velhagen plates, and the Standard Pseudoisochromatic Plates Part 2. Results Median toluene concentration was 1.59 mg/l (quartiles 0.78 and 2.65). The whole group of workers did not perform worse than the controls. The same applies to 20 printers, who regularly assessed hues. Assessed with the most sensitive Lanthony panel D-15 desaturated test, color vision of 24 permanently exposed assistants was impaired (median color confusion index of the 1st eyes 1.08 vs. 1.02, p < 0.02; 2nd eyes 1.08 vs. 1.0, p < 0.05; sign test). The assistants made almost exclusively blue–yellow errors. The other color vision tests did not reveal any differences between the groups. Conclusion Changes in the retina are a possible explanation for the observed blue–yellow dyschromatopsia.

Emotional demands and exhaustion: cross-sectional and longitudinal associations in a cohort of Danish public sector employees Abstract Purpose To examine cross-sectional and longitudinal associations between content-related emotional demands at work and exhaustion, and to investigate if these associations were modified by other psychosocial work characteristics. Methods In 2007, 4489 Danish public service employees participated in the PRISME study by completing postal questionnaires, and 3224 participated in the follow-up in 2009. Content-related emotional demands were measured by a scale (scored 1 to 5) based on five work-content-related items, and exhaustion was measured with the general exhaustion scale from the Copenhagen Burnout Inventory (CBI) (scored 1 to 5). The cross-sectional and longitudinal associations with exhaustion were analysed in the same model and adjusted for effects of potential confounders. Effect modifications were examined separately for self-reported emotional enrichment, meaningful work, job control, social support at work and quantitative demands. Results Exhaustion increased with increasing emotional demands, both cross-sectionally and longitudinally. However, although statistically significant, the effect was small. In the longitudinal analysis, a one unit increase in emotional demands was associated with a 0.03 unit (95% CI: 0.01–0.06) increase in exhaustion. We found statistically significant effect modification for three of six potentially modifying work characteristics. The effect of emotional demands on exhaustion was lower for participants with high levels of emotional enrichment (cross-sectionally and longitudinally), high levels of meaningful work (longitudinally), and higher for high levels of quantitative demands (cross-sectionally). Conclusions Increasing content-related emotional demands were associated with increasing levels of exhaustion, cross-sectionally and longitudinally. This effect was reduced if the work was experienced as emotionally enriching and meaningful.

The influence of wind turbine visibility on the health of local residents: a systematic review Abstract Purpose The health effects of visible wind turbine features on residents were investigated. Further, it was examined, if visual annoyance has an influence on residents' health, and if wind turbine visibility impacts residents' health independently of or in combination with acoustical aspects. Methods Medical databases, Google Scholar, public health institutions, and reference lists were searched systematically (PROSPERO registry number: CRD42016041737). Two independent reviewers screened titles/abstract and full texts, extracted data, and critically appraised the methodology of included studies. Study findings were analyzed qualitatively and quantitatively. Results Seventeen studies from 19 publications of varying methodological quality were included (two cohort studies, fifteen cross-sectional studies). The pooled prevalence of high annoyance due to altered views and shadow flicker was 6% each. The results of other health effects were inconsistent, with some indications showing that direct wind turbine visibility increases sleep disturbance. Annoyance by direct visibility, shadow flicker, and blinking lights was significantly associated with an increased risk for sleep disorders. One study indicated reactions to visual wind turbine features may be influenced by acoustical exposures. Conclusions In interpreting the results, the differing methodological quality of the included studies needs to be considered. Direct and indirect wind turbine visibility may affect residents' health, and reactions may differ in combination with noise. Further, annoyance by wind turbine visibility may interact as mediator between visual exposures and the health of local residents. To confirm the results, more high-quality research is needed.

Relationships of leisure-time physical activity and work ability between different occupational physical demands in adult working men Abstract Purpose Leisure-time physical activity (LTPA) is known to be associated with positive health benefits, but the role of occupational physical demands remains inconsistent. The purpose of the current study was to assess the relationship between LTPA and work ability in different occupational physical activity (OPA) levels between young adult men. Methods We performed physical activity measurements in work and leisure time with the long version of International Physical Activity Questionnaire (IPAQ) and work ability with the Work Ability Index (WAI) in 921 Finnish employed male volunteer participants. The participants were divided into LTPA tertiles I (< 8 MET-h/week), II (8–28 MET-h/week), and III (> 28 MET-h/week) and OPA tertiles I (0 MET-h/week), II (< 64 MET-h/week), and III (≥ 64 MET-h/week). Results There was a significant relationship between LTPA and WAI in OPA tertiles (adjusted for age, alcohol consumption, working class status, BMI, and employment years). Moreover, each LTPA tertile showed significant linear associations with WAI (P < 0.001). Conclusion LTPA is positively associated with work ability among young adult men. More specifically, the relationships between LTPA and WAI were significantly greater in physically demanding jobs than in more passive jobs. Our results indicate the importance of LTPA, particularly with individuals under higher work-related physical strain.

Cumulative physical workload and mobility limitations in middle-aged men and women: a population-based study with retrospective assessment of workload Abstract Purpose To assess the association between exposure to physical workload throughout working life and risk of mobility limitations in midlife in a population-based Danish cohort. Methods The study was cross-sectional with a retrospective exposure assessment, and data were from a questionnaire used in the Copenhagen Aging and Biobank. Cumulative physical workload was estimated by combining information about the participants' employments and data from a job exposure matrix. Daily amount of lifting was standardised in ton-years (lifting 1000 kg/day/year) and grouped in 5 exposure groups (no/minor (1–2 ton-years)/low (3–10 ton-years)/moderate (11–20 ton-years)/high exposure (> 20 ton-years)). The outcome was self-reports of mobility limitations (running 100 m, walking 400 m, and climbing stairs to the 2nd floor) in midlife. The association between exposure and outcome was analysed using logistic regression models. Results We included 4996 men and 2247 women, mean age 56 years. 21% of men and 10% of women were in the highest exposure-group (> 20 ton-years). Higher cumulative exposure was associated with higher odds for mobility limitations. Exposure to more than 20 ton-years compared to no exposure increased the odds for limitations in walking, age-adjusted odds ratio (OR) 3.2 (95% CI: 2.4–4.3) for men, 2.3 (1.4–3.8) for women. Corresponding results for running: 2.5 (2.2–3.0) for men, 1.6 (1.2–2.2) for women, and for limitations in climbing stairs: 4.2 (3.3–5.2) for men, 1.7 (1.2–2.4) for women. Results were attenuated when confounders were added. Conclusions Exposure to physical workload throughout working life is associated with higher odds for mobility limitations in midlife.

Long working hours and depressive symptoms: moderating effects of gender, socioeconomic status, and job resources Abstract Purpose Systematic reviews and meta-analyses have found inconsistent associations between working hours and depressive symptoms. The purpose of this study was to investigate the possible moderators of this association, using data from a large-scale cross-sectional survey. Methods A total of 16,136 Japanese employees (men 83.5%; women 16.5%) responded to a self-administered questionnaire inquiring about overtime working hours during the previous month and depressive symptoms (Center for Epidemiologic Studies Depression scale), as well as moderating factors including gender, age, marital status, socioeconomic status, commuting time, sleeping hours per day, job control and worksite social support (Job Content Questionnaire), neuroticism (Eysenck's Personality Questionnaire Revised), and social desirability (Social Desirability Scale) (response rate, 85%). We conducted sequential regression analyses to investigate the main effects and interaction effects of all moderating variables. Results The association between overtime working hours and depressive symptoms was significantly moderated by gender (interaction effect: β = 0.03), age (β = − 0.02), manager (β = 0.03), sleeping hours (β = − 0.02), job control (β = − 0.03), and neuroticism (β = 0.02). Among workers engaged in 80 + hours of overtime, higher depressive symptoms were reported by women, younger employees, non-managers, employees with low job control, low worksite social support, and high neuroticism. A significant main effect of long overtime working hours on depressive symptoms was also observed even after controlling for all independent variables (β = 0.02). Conclusions Long overtime working hours is associated with depressive symptoms. We also found significant heterogeneity in the association according to employee characteristics, which may explain the inconsistent findings in previous literature.

Association between the return-to-work hierarchy and self-rated health, self-esteem, and self-efficacy Abstract Purpose This study aimed to examine whether change of employer and/or job upon return-to-work after work-related injuries and diseases is related to health outcomes; self-rated health, self-esteem, and self-efficacy were used as indicators. Methods Data from the Panel Study of Workers' Compensation Insurance in Korea were used. A total of 1,610 workers who had returned to work after work-related injuries and diseases were included. The workers were divided into four groups according to their return-to-work characteristics: same employer, same job (n = 660); same employer, different job (n = 57); different employer, same job (n = 318); and different employer, different job (n = 575). Self-rated health, Rosenberg Self-Esteem Scale, and Self-Efficacy Scale scores were used as outcome variables. Logistic regression analysis was used. Results Compared to workers who had returned to the same employer and same job, those who had returned to the same employer but a different job were less likely to report good self-rated health (odds ratio [OR] 0.54; confidence interval [CI] 0.30–0.97). Those returning to a different employer but the same job were less likely to report good self-rated health (0.47, 0.35–0.64) and high self-esteem (0.73, 0.55–0.96). Those returning to a different employer and different job were less likely to report good self-rated health (0.49, 0.38–0.63), high self-esteem (0.68, 0.54–0.86), and high self-efficacy (0.66, 0.52–0.83). Conclusions Change of employer and/or job related to health outcomes. Returning to the same employer and same job should be set as a goal in the vocational rehabilitation process.

Enhancing medical evaluations of sick-listed employees: an educational intervention to improve professional practice of physicians performing work ability assessments of employees on long-term sick leave Abstract Purpose Long-term sick leave (LTSL) is a complex phenomenon. Medical and non-medical factors can delay return-to-work (RTW); therefore, the assessment of work ability is complicated. A checklist for identifying factors associated with delayed RTW was developed in a prior study to facilitate the exploration of barriers and facilitators for RTW. The purpose of the present study was to determine if use of the checklist enhances professional practice of physicians performing work ability assessments of employees on long-term sick leave and whether the reporting of work ability assessments improved when using the checklist in the routinely practice-based context. Methods An educational intervention study was performed using qualitative framework analysis. Thirty-five Dutch physicians were asked to identify and report the barriers and facilitators for RTW and the consequences for the work ability and for the prognosis regarding work reintegration using the checklist. A pre-post qualitative analysis of the medical records was performed using a gradual classification of the reporting of the work ability to evaluate the change in reporting following the educational intervention. Results A total of 337 work ability assessments were performed using the checklist. The identification of factors influencing RTW and the comprehensiveness of the medical records increased when compared with the reporting before the educational intervention. The reporting of the work ability assessments improved after the educational intervention. Most physicians reported at least one of the factors of the checklist. 72% participants reported and described adequately at least one factor. 48% participants reported how the factors influenced the work ability, 20% participants reported how the factors influenced the prognosis regarding RTW and 12% participants reported which advice was provided by the physician to influence the barriers for RTW. Conclusions Use of the checklist enhances professional practice of physicians performing work ability assessments of employees on long-term sick leave and is associated with increased identification of barriers and facilitators for RTW. The use of the checklist should be considered to improve professional practice of physicians performing work ability assessments.

An educational intervention to improve knowledge about prevention against occupational asthma and allergies using targeted maximum likelihood estimation Abstract Purpose Occupational asthma and allergies are potentially preventable diseases affecting 5–15% of the working population. However, the use of preventive measures is often insufficient. The aim of this study was to estimate the average treatment effect of an educational intervention designed to improve the knowledge of preventive measures against asthma and allergies in farm apprentices from Bavaria (Southern Germany). Methods Farm apprentices at Bavarian farm schools were asked to complete a questionnaire evaluating their knowledge about preventive measures against occupational asthma and allergies (use of personal protective equipment, personal and workplace hygiene measures). Eligible apprentices were randomized by school site to either a control or an intervention group. The intervention consisted of a short educational video about use of preventive measures. Six months after the intervention, subjects were asked to complete a post-intervention questionnaire. Of the 116 apprentices (70 intervention group, 46 control group) who answered the baseline questionnaire, only 47 subjects (41%; 17 intervention group, 30 control group) also completed the follow-up questionnaire. We, therefore, estimated the causal effect of the intervention using targeted maximum likelihood estimation. Models were controlled for potential confounders. Results Based on the targeted maximum likelihood estimation, the intervention would have increased the proportion of correct answers on all six preventive measures by 18.4% (95% confidence interval 7.3–29.6%) had all participants received the intervention vs. had they all been in the control group. Conclusions These findings indicate the improvement of knowledge by the educational intervention.

Low radon exposures and lung cancer risk: joint analysis of the Czech, French, and Beaverlodge cohorts of uranium miners Abstract It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013–0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon–lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

PharmacoEconomics

Correction to: Are Quality-Adjusted Life Years a Good Proxy Measure of Individual Capabilities? Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0International License

Correction to: Different Methods for Modelling Severe Hypoglycaemic Events: Implications for Effectiveness, Costs and Health Utilities The Open Access license, which previously read

Correction to: Sensitivity Analysis for Not-at-Random Missing Data in Trial-Based Cost-Effectiveness Analysis: A Tutorial The Open Access license, which previously read.

Response to 'Comment on "Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States"'

Comment on "Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States"

Economic Evaluation of the 2016 Chinese Guideline and Alternative Risk Thresholds of Initiating Statin Therapy for the Management of Atherosclerotic Cardiovascular Disease Abstract Objective The 2016 Chinese guidelines for the management of dyslipidemia recommended mixed rules that centered around a 10% 10-year risk threshold to initiate statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). The present study aimed to evaluate the cost-effectiveness of the guideline statin-initiation strategy and alternative strategies. Methods A decision analytic model using discrete event simulation with event probabilities based on a validated ASCVD risk prediction tool for Chinese was constructed. Risk factor inputs were from the dataset of a nationally representative survey of middle-aged and elderly Chinese. Data of statin treatment effectiveness were from a published meta-analysis. Other key input data were identified from the literature or relevant databases. The strategies we evaluated were the guideline strategy, a 15% 10-year risk threshold strategy and a 20% 10-year risk threshold strategy. After excluding any extended dominance strategies, the incremental costs per quality-adjusted life year (QALY) gained of each strategy was calculated. Results The 20% 10-year risk threshold strategy was an extended dominance option. The incremental costs per QALY gained from the 15% 10-year risk threshold strategy compared with no treatment and the guideline strategy compared with the 15% 10-year risk threshold strategy were CN¥69,309 and CN¥154,944, respectively. The results were robust in most sensitivity analyses. Conclusions The guideline strategy and the 15% 10-year risk threshold strategy are optimal when using the three times and the two times the gross domestic product per capita willingness-to-pay standards, respectively.

The Curve of Optimal Sample Size (COSS): A Graphical Representation of the Optimal Sample Size from a Value of Information Analysis Abstract Value of information (VOI) analysis quantifies the opportunity cost associated with decision uncertainty, and thus informs the value of collecting further information to avoid this cost. VOI can inform study design, optimal sample size selection, and research prioritization. Recent methodological advances have reduced the computational burden of conducting VOI analysis and have made it easier to evaluate the expected value of sample information, the expected net benefit of sampling, and the optimal sample size of a study design ( \(n^{*}\) ). The volume of VOI analyses being published is increasing, and there is now a need for VOI studies to conduct sensitivity analyses on VOI-specific parameters. In this practical application, we introduce the curve of optimal sample size (COSS), which is a graphical representation of \(n^{*}\) over a range of willingness-to-pay thresholds and VOI parameters (example data and R code are provided). In a single figure, the COSS presents summary data for decision makers to determine the sample size that optimizes research funding given their operating characteristics. The COSS also presents variation in the optimal sample size given variability or uncertainty in VOI parameters. The COSS represents an efficient and additional approach for summarizing results from a VOI analysis.

Estimating Quality of Life Decrements Due to Diabetes Complications in the United States: The Health Utility Index (HUI) Diabetes Complication Equation Abstract Objective Health utility decrements associated with diabetes mellitus complications are essential for calculating quality-adjusted life-years (QALYs) in patients for use in economic evaluation of diabetes interventions. Previous studies mostly focused on assessing the impact of complications on health utility at event year based on cross-sectional data. This study aimed to separately estimate health utility decrements associated with current and previous diabetes complications. Research Design and Methods The Health Utilities Index Mark 3 (HUI-3) was used to measure heath utility in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 8713). Five macrovascular complications (myocardial infarction [MI], congestive heart failure [CHF], stroke, angina, and revascularization surgery [RS]) and three microvascular complications (nephropathy [renal failure], retinopathy [severe vision loss], and neuropathy [severe pressure sensation loss]) were included in a set of alternative modelling approaches including the ordinary least squares (OLS) model, fixed effects model, and random effects model to estimate the complication-related health utility decrements. Results All macrovascular complications were associated with decrements of HUI-3 scores: MI (event year: − 0.042, successive years: − 0.011), CHF (event year: − 0.089, successive years: − 0.041), stroke (event year: − 0.204, successive years: − 0.101), angina (event year: − 0.010, successive years: − 0.032), and revascularization (event year: − 0.038, successive years: − 0.016) (all p < 0.05). For microvascular complications, severe vision loss (− 0.057), and severe pressure sensation loss (− 0.066) were significantly associated with decrements of HUI-3 scores (both p < 0.05). Hypoglycemia (both severe and symptomatic) was found to be associated with a 0.036 decrement of health utility at event year, and a 0.033 decrement of health utility at successive years. Results from an OLS model are preferred for supporting a microsimulation model while a fixed effects model is preferred to describe direct health impacts from complications. Conclusions Macrovascular and microvascular complications caused QALY decrements in patients with type 2 diabetes. While only part of the total impaired QALY is experienced during the event year, further QALY decrements for successive years were quite substantial.

Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal Abstract Chondrosphere (Spherox) is a form of autologous chondrocyte implantation (ACI). It is licensed for repair of symptomatic articular cartilage defects of the femoral condyle and the patella of the knee with defect sizes up to 10 cm2 in adults. In a single technology appraisal (STA) [TA508] undertaken by the National Institute of Health and Care Excellence (NICE), Warwick Evidence was the Evidence Review Group (ERG) invited to independently review the evidence submitted by the manufacturer, Co.Don. The clinical effectiveness data came from their COWISI randomised controlled trial (RCT), which compared Chondrosphere with microfracture (MF). The timing of this appraisal was unfortunate given that MF was no longer the most relevant comparator because NICE had contemporaneously published guidance approving ACI in place of MF. Moreover, the COWISI RCT enrolled mostly patients with small defect sizes. Evidence of clinical effectiveness for Chondrosphere used in people with larger defect size came from another RCT, which compared three doses of Chondrosphere and that by design could not provide evidence comparing Chondrosphere to any other forms of ACI. To estimate the relative clinical performance of Chondrosphere versus other ACI, Co.Don conducted an indirect treatment comparison by network meta-analyses (NMA). The NMA was flawed in that the distribution of population characteristics that are effect modifiers greatly differed across the treatment comparisons of the network. The ERG questioned both the appropriateness of the NMA and the validity of the resulting estimates. Co.Don estimated the cost-effectiveness of Chondrosphere using a lifetime Markov model with all patients receiving the first repair during the first cycle of the model then moving into one of three health states: success, no further repair (NFR), or a second repair, if necessary. Subsequent to the first cycle, those who were a success either remained a success or moved to second repair. All those in NFR remained in NFR. The cost-effectiveness of Chondrosphere compared to other ACI forms relied on the clinical effectiveness estimates of success and failure rates obtained from the company's indirect comparisons, the validity of which the ERG questioned. The company revised cost-effectiveness estimates for Chondrosphere versus MF and for Chondrosphere versus matrix-applied characterised autologous cultured chondrocyte implant (MACI) were £4360 and around £18,000 per quality-adjusted life year gained, respectively. NICE recommended ACI using Chondrosphere for treating symptomatic articular cartilage defects of the femoral condyle and patella of the knee in adults only if certain requirements were met.

A Systematic Review of Direct Cardiovascular Event Costs: An International Perspective Abstract Introduction There is a lack of comprehensive cost information for cardiovascular events since 2013. Objective A systematic review on the contemporary cost of cardiovascular events was therefore undertaken. Methods Methods complied with those recommended by the Cochrane Collaboration and the Centre for Reviews and Dissemination. Studies were unrestricted by language, were from 2013 to 23 December 2017, and included cost-of-illness data in adults with the following cardiovascular conditions: myocardial infarction (MI), stroke, transient ischaemic attack (TIA), heart failure (HF), unstable angina (UA), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), or peripheral artery disease (PAD). Seven electronic databases were searched, namely Embase (Ovid), MEDLINE (Ovid), MEDLINE In-Process Citations and Daily Update (Ovid), NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) database, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. The included studies reported data from a variety of years (sometimes prior to 2013), so costs were inflated and converted to $US, year 2018 values, for standardization. Results After de-duplication, 29,945 titles and abstracts and then 403 full papers were screened; 82 studies (88 papers) were extracted. Year 1 average cost ranges were as follows: MI ($11,970 in Sweden to $61,864 in the USA), stroke ($10,162 in Spain to $46,162 in the USA), TIA ($6049 in Sweden to $25,306 in the USA), HF ($4456 in China to $49,427 in the USA), UA ($11,237 in Sweden to $31,860 in the USA), PCI ($17,923 in Italy to $45,533 in the USA), CABG ($17,972 in the UK to $76,279 in the USA). One Swedish study reported PAD costs in a format convertible to $US, 2018 values, with a mean annual cost of $15,565. Conclusions There was considerable unexplained variation in contemporary costs for all major cardiovascular events. One emerging theme was that average costs in the USA were considerably higher than anywhere else.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Thrombosis and Thrombolysis

Correction to: Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta-analysis The article Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta‑analysis, written by Xin Cao, Jun Zhang and Daoying Geng, was originally published electronically on the publisher's internet portal (currently SpringerLink) on April 2019 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on May 2019 to © Springer Science+Business Media, LLC, part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright

Highlights from the 2019 American College of Cardiology Scientific Sessions in New Orleans, LA

Drug-eluting stents versus bare-metal stents with a single month of dual antiplatelet therapy: a trial sequential analysis

Exosome mediated differentiation of megakaryocytes: a study on TLR mediated effects Abstract Megakaryocytes are large polyploid bone marrow cells whose function is to produce circulatory platelets. Megakaryocytes are also known to release extracellular vesicles (EVs) of varying sizes. Toll like receptors (TLRs), present on the sentinel cells are essential components of the innate immune response, these receptors are also expressed by platelets and megakaryocytes. Our data provide the evidence that TLR-2 induced MKEVs are able to recapitulate TLR-2 signalling in megakaryocytic cell line (Dami cells) and that likely induces megakaryocytic maturation by increasing the production of cytokines involved in MK maturation. TLR-2 induced MKEVs may be involved in replenishment of the immune effector platelets in circulation and its progenitor megakaryocyte in bone marrow for the physiological need of the platelets by inducing the maturation of megakaryocyte.

Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians Abstract Von Willebrand Factor (vWF) is a large glycoprotein with a broad range of physiological and pathological functions in health and disease. While vWF is critical for normal hemostasis, vascular integrity and repair, quantitative and qualitative abnormalities in the molecule can predispose to serious bleeding and thrombosis. The heritable form of von Willebrand Disease was first described nearly a century ago, but more recently, recognition of an acquired condition known as acquired von Willebrand Syndrome (AVWF) has emerged in persons with hematological, endocrine and cardiovascular diseases, disorders and conditions. An in-depth understanding of the causes, diagnostic approach and management of AVWS is important for practicing clinicians.

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis Abstract De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2–28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1–4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4–4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.

Body mass index reduction improves the baseline procoagulant imbalance of obese subjects Abstract Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e., hypercoagulability). Information on hypercoagulability associated with obesity is scanty and mainly based on global traditional coagulation tests or on the measurement of individual components of coagulation (i.e., pro- and anticoagulants). Plasma from 33 obese subjects was investigated soon before endoscopic balloon placement and after removal (6 months later) by thrombin-generation procedures that are thought to represent much better than any other in vitro test the coagulation process occurring in vivo. We found that obese subjects possess a state of hypercoagulability as demonstrated by the modification of the main parameters of thrombin-generation. In particular, the median value (min–max) of the endogenous thrombin potential (ETP) of obese subjects at baseline was higher than that of controls [1968 (1335–2533) vs. 1710 (1010–2119), p < 0.001]. Endoscopic balloon placement achieved a BMI reduction from 38.9 (31.7–62.3) to 31.6 (21.9–53.3), p < 0.001 and a parallel reduction of thrombin-generation as demonstrated by the following findings. The ETP measured soon after balloon removal was significantly smaller than that measured at baseline [1783 (1224–2642) vs. 1968 (1335–2533), p < 0.01]. The other parameters of thrombin-generation, including lag-time, peak-thrombin, time-to-reach the peak and velocity index showed a pattern consistent with the ETP, both at baseline and soon after balloon removal. Endoscopic balloon placement achieves concomitant reduction of BMI and thrombin-generation in subjects with obesity.

Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis Abstract Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30–85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21–2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.

Normal D-dimer levels in cancer patients with radiologic evidence of pulmonary embolism Abstract Accurate and expeditious diagnosis and treatment of pulmonary embolism in cancer patients improves patient outcomes. D-dimer is often used to rule out pulmonary embolism. However, this test is less accurate in cancer patients, and it is unclear whether cancer patients with normal D-dimer levels can present with pulmonary embolism. All consecutive patients who presented to The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, between May 2009 and November 2015 who underwent computed tomography pulmonary angiography and plasma D-dimer level measurement were retrospectively reviewed. Patients with suspected pulmonary embolism and normal D-dimer levels were identified. Among the 8023 cancer patients identified, 1156 (14%) had pulmonary embolism. Only 35 patients with pulmonary embolism (3%) had normal plasma D-dimer levels. Twenty-six of these patients had acute pulmonary embolism and the other nine had subacute or chronic pulmonary embolism. Thirteen of the 26 acute cases were in patients with hematological cancer. Most patients (23/35, 66%) had subsegmental or segmental pulmonary embolism. Only one patient had pulmonary embolism in the main pulmonary arteries. Although it is uncommon (3%), cancer patients with radiologic evidence of pulmonary embolism can present with normal D-dimer levels. Recognizing the possibility of this uncommon occurrence is critical in the decision process for ordering diagnostic tests for evaluation of suspected pulmonary embolism.

A direct oral anticoagulant edoxaban accelerated fibrinolysis via enhancement of plasmin generation in human plasma: dependent on thrombin-activatable fibrinolysis inhibitor Abstract A direct oral anticoagulant, edoxaban, is as effective as vitamin K antagonists for the treatment of venous thromboembolism (VTE). However, the mechanism underlying the treatment effect on VTE remains to be determined. The aims of this study were to evaluate the effect of edoxaban on tissue plasminogen activator (t-PA)-induced clot lysis in human plasma and to determine the roles of plasmin and thrombin-activatable fibrinolysis inhibitor (TAFI) in the profibrinolytic effect by edoxaban. Pooled human normal plasma or TAFI-deficient plasma (containing 180 ng/mL t-PA and 0.1 nM thrombomodulin) was mixed with edoxaban or an activated TAFI inhibitor, potato tuber carboxypeptidase inhibitor (PCI). Clot was induced by adding tissue factor and phospholipids. Clot lysis time and plasma plasmin-α2 antiplasmin complex (PAP) concentration were determined. Clot structure was imaged with a scanning electron microscope. In normal plasma, edoxaban at clinically relevant concentrations (75, 150, and 300 ng/mL) and PCI significantly shortened clot lysis time. PCI increased PAP concentration and a correlation between PAP concentration and percent of clot lysis was observed. Edoxaban also dose-dependently elevated PAP concentration. In TAFI-deficient plasma, the effects of edoxaban and PCI on clot lysis and PAP concentration were markedly diminished as compared with normal plasma. Fibrin fibers were thinner in clots formed in the presence of edoxaban. In conclusion, edoxaban at clinically relevant concentrations accelerates t-PA-induced fibrinolysis via increasing plasmin generation in human plasma. The effects of edoxaban is mainly dependent on TAFI. The profibrinolytic effect of edoxaban might contribute to the efficacy for the treatment of VTE.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com