Feasibility study of computational occupational dosimetry: evaluating a proof-of-concept in an endovascular and interventional cardiology setting.

Individual monitoring of radiation workers is essential to ensure compliance with legal dose limits and to ensure that doses are As Low As Reasonably Achievable. However, large uncertainties still exist in personal dosimetry and there are issues with compliance and incorrect wearing of dosimeters. The objective of the PODIUM (Personal Online Dosimetry Using Computational Methods) project was to improve personal dosimetry by an innovative approach: the development of an online dosimetry application based on computer simulations without the use of physical dosimeters. Occupational doses were calculated based on the use of camera tracking devices, flexible individualised phantoms and data from the radiation source. When combined with fast Monte Carlo simulation codes, the aim was to perform personal dosimetry in real-time. A key component of the PODIUM project was to assess and validate the methodology in interventional radiology workplaces where improvements in dosimetry are needed. This paper describes the feasibility of implementing the PODIUM approach in a clinical setting. Validation was carried out using dosimeters worn by Vascular Surgeons and Interventional Cardiologists during patient procedures at a hospital in Ireland. Our preliminary results from this feasibility study show acceptable differences of the order of 40% between calculated and measured staff doses, in terms of the personal dose equivalent quantity Hp(10), however there is a greater deviation for more complex cases and improvements are needed. The challenges of using the system in busy interventional rooms have informed the future needs and applicability of PODIUM. The availability of an online personal dosimetry application has the potential to overcome problems that arise from the use of current dosimeters. In addition, it should increase awareness of radiation protection among staff. Some limitations remain and a second phase of development would be required to bring the PODIUM method into operation in a hospital setting. However, an early prototype system has been tested in a clinical setting and the results from this two-year proof-of-concept PODIUM project are very promising for future development.

Early and mid-term outcomes after transcatheter aortic valve implantation (TAVI) in Ireland.

BACKGROUND: TAVI is a percutaneous approach to aortic valve replacement in high surgical risk patients deemed inoperable. AIM: To evaluate the early and mid-term outcomes for an Irish TAVI cohort over a six-year period at St James's Hospital and Blackrock Clinic, Dublin, Ireland. RESULTS: In total 147 patients, 56% male with an average age of 82 underwent TAVI between December 2008 and December 2014. Thirty day, one year and two year survival was 90.5%, 83% and 71% respectively. Major vascular complications and renal failure were the biggest predictors of mortality at 30 days (p = 0.02). We observed a pacing rate of 13.5%, the majority in patients who had Medtronic Corevalve implants (p < 0.05). With increasing procedural experience there was a reduction in length of stay from 10 days to 7.5 days. CONCLUSION: This review, the first of its kind in Ireland showed favorable rates of 30 day and one year and two year survival post TAVI with procedural success and complication rates similar to international registry data.

Safety of therapeutic hypothermia in post VF/VT cardiac arrest patients.

Therapeutic hypothermia (TH) is a process of cooling a patient post ventricular tachycardia/ventricular fibrillation (VT/VF) cardiac arrest to 32-34 degrees C for 24 hours. This improves neurological outcome and is part of current guidelines. Hypothermia prolongs QT interval, which can precipitate torsades de pointes (TdP). We performed a retrospective review of all patients who received TH in our hospital over a period of 2 years to assess the effect of TH on the corrected OT interval (QTc) and any possible pro-arrhythmia. A total of 13 patients received TH. QTc prolonged in all patients with an average of 80.3 + 57.2 ms., and up to 109.8 + 80.4 ms in patients who received Amiodarone concurrently. No TdP was seen in any patient. We conclude that TH is safe, though careful monitoring of the OTc interval is advisable especially with concurrent use of QT prolonging drugs.

High sensitivity cytokine detection in acute coronary syndrome reveals up-regulation of interferon gamma and interleukin-10 post myocardial infarction.

Inflammation is an important element in the development and destabilization of atherosclerotic plaque. Using a high sensitivity multiplex assay, previously untested in the context of atherosclerotic disease, we determined serum concentrations of GM-CSF, IFNgamma, IL-1beta, IL-2, IL-10, IL-12p70, TNF alpha, IL-6, and IL-8 in 48 Myocardial Infarction (MI) patients, 14 Unstable Angina (UA) patients and 12 healthy controls. IFNgamma levels were significantly higher in MI compared to UA (p=0.0091) and Control groups (p=0.0014). IL-10 also showed higher expression levels between MI, UA groups and Controls (p=0.0299).This up-regulation may reflect the extent of plaque instability and/or rupture in MI patients.Our observations provide evidence that IFNgamma and IL-10 merit further investigation in atherosclerotic disease states as potential markers of disease and therapeutic targets.

Alterations in myocardial stiffness in elite athletes assessed by a new Doppler index.

BACKGROUND: In elite athletes left ventricular (LV) morphological changes are predicted to alter passive pressure/volume characteristics by reducing myocardial stiffness and increasing compliance. OBJECTIVE: To investigate the utility of a new Doppler tissue index based on the pressure volume relation ((E/Ea)/LVEDD), which provides a measure of myocardial stiffness, and to assess its usefulness in detecting cardiac adaptation in elite rowers. METHODS: Thirty-six international rowers who had trained intensively and a control group of 30 sedentary subjects, matched for age and sex, were enrolled in the study. LV septal and posterior wall thickness, mass, chamber size, transmitral Doppler peak early (E) and late (A) diastolic filling velocities and isovolumic relaxation times were measured. Early diastolic myocardial velocities (Ea) were averaged from four sites at the mitral annulus; diastolic stiffness was assessed with the use of three indices E, Ea and the LV end-diastolic diameter in diastole (LVEDD). The ratio, (E/Ea)/LVEDD, provides a new index of diastolic stiffness. Rowers were further divided into two groups based on the presence or absence of left ventricular hypertrophy (LVH) 12 mm. RESULTS: No significant difference in Ea was found between the two groups, but there was a difference in the stiffness index, which remained after adjustment for body surface area and heart rate (controls 1.48 (0.3) vs athletes 1.17 (0.34), p = 0.016). No difference in stiffness index was found between the groups with LVH 12 mm (1.11 (0.32) vs 1.17 (0.34), respectively, p = 0.68) CONCLUSIONS: Intense training reduces myocardial stiffness despite the development of LVH.

Prevalence and clinical significance of systolic impairment in hypertrophic cardiomyopathy.

OBJECTIVES: To determine the frequency of systolic impairment (SI) and its impact on the natural history of hypertrophic cardiomyopathy (HCM). METHODS: 1080 patients (mean (SD) age 43 (15) years, 660 men) with HCM were evaluated. Initial assessment included history, examination, 48 hour Holter monitoring, cardiopulmonary exercise testing, and echocardiography; SI was defined as a fractional shortening (FS) < or = 25%. Survival data were collected at clinic visits or by direct communication with patients and their general practitioners. The results of serial echocardiography in 462 patients with normal FS at presentation are also reported. RESULTS: 26 (2.4%) patients (49 (14) years, 18 men) had SI at the initial visit. During follow up (58 (49) months), nine (34.6%) died or underwent cardiac transplantation compared with 108 (10.2%) patients with normal FS (p = 0.01). Five year survival from death (any cause) or transplantation was 90.1% (95% confidence interval (CI) 87.8 to 92.4) in patients with normal systolic function versus 52.4% (95% CI 25.2 to 79.6, p < 0.0001) in patients with SI. In patients who underwent serial echocardiography, 22 (4.8%, aged 41 (15) years) developed SI over 66 (40) months; the annual incidence of SI was 0.87% (95% CI 0.54 to 1.31). On initial evaluation patients who developed SI had a higher frequency of syncope (67 (15.2%) v 10 (45.5%) of those who did not develop SI, p = 0.001), non-sustained ventricular tachycardia (91 (20.6%) v 11 (50%), p = 0.002), and an abnormal blood pressure response on exercise (131 (29.7%) v 15 (68.2%), p = 0.001). Patients with SI had greater wall thinning (p = 0.001), left ventricular cavity enlargement (p < 0.0005), and deterioration in New York Heart Association functional class (p = 0.001) during follow up. Thirteen (59.1%) patients who progressed to SI died or underwent transplantation compared with 38 (8.6%) patients who maintained normal systolic function. CONCLUSIONS: SI is an infrequent complication of HCM but, when present, is associated with a poor prognosis.

Audit of acute myocardial infarctions at Saint James's Hospital, Dublin, from 1996 to 1999.

Saint James' Hospital is a 650-bed tertiary referral hospital. An audit was performed of acute transmural myocardial infarctions for the years 1996 to 1999 inclusive. On average there were 2043 cardiology admissions annually, 9.8% of all hospital admissions. Acute transmural myocardial infarction was diagnosed in 178 patients annually, and was less common during the summer. The figure of 72% receiving revascularisation therapy (thrombolysis 67%, primary angioplasty 5%) compares favourably with 35% in 1992. The main reason for not receiving thrombolysis was late presentation (15%) with contraindications present in only 5%. The case fatality rate was 16% confirming the higher mortality in clinical practice than that of thrombolytic trials. The prescription of aspirin or warfarin (99%) and betablockers (67%) was in line with international trials. The use of angiotensin converting enzyme inhibitors (34%) and statins (28%) is similar to other studies but less than would be expected according to trial evidence.

Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules.

OBJECTIVE: To assess prospectively the prognostic value of soluble cellular adhesion molecules (CAMs) in patients with unstable angina and non-Q wave myocardial infarction and to compare their prognostic accuracy with that of C reactive protein (CRP). DESIGN AND SETTING: Prospective observational study of patients presenting acutely with unstable angina and non-Q wave myocardial infarction to a single south Dublin hospital. METHODS: Patients with Braunwald IIIA unstable angina and non-Q wave myocardial infarction had serum samples taken at presentation before initiation of antithrombotic treatment and were followed for six months. The primary end point was the occurrence of major adverse cardiovascular events (recurrent unstable angina, non-fatal myocardial infarction, and cardiovascular death) at six months. Concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble endothelial selectin, and soluble platelet selectin were measured using an enzyme linked immunosorbent assay technique. CRP was measured with an immunophelometric assay. RESULTS: 91 patients (73 men and 18 women, mean (SD) age 61 (11) years) were studied; 27 patients (30%) had major adverse cardiac events during the six months of follow up. Concentration of CRP were significantly raised in patients who had an ischaemic event (mean (SEM) 11.5 (6.4) mg/l v 5.4 (2.5) mg/l, p < 0.001). Concentrations of sVCAM-1 were also significantly raised in the ischaemic event group (979 (30) ng/ml v 729 (22) ng/ml, p < 0.001). Both sVCAM-1 and CRP concentrations correlated strongly with the occurrence of an adverse event. The sensitivity of CRP > 3 mg/l and sVCAM-1 > 780 ng/ml for predicting future events was > 90%. There was no difference in concentrations of sICAM-1, soluble endothelin selectin, or soluble platelet selectin between event and non-event groups. CONCLUSION: Raised concentrations of sVCAM-1 and CRP are predictive of an increased risk of major adverse cardiovascular events six months after presentation with unstable angina and non-Q wave myocardial infarction. These findings suggest that the intensity of the vascular inflammatory process at the time of presentation is a determinant of clinical outcome in unstable coronary artery disease.

Occupancy of the internal and external pools of glycoprotein IIb/IIIa following abciximab bolus and infusion.

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.

Impact of preexisting statin use on adhesion molecule expression in patients presenting with acute coronary syndromes.

Of 147 patients admitted with acute coronary syndromes, 17 were taking statins at the time of presentation. These were matched with 17 subjects not taking statins. We found that statin therapy was associated with lower levels of sP-selectin, a marker of platelet and vascular endothelial activation. This provides further insight into the extralipid effect of statins in clinical practice and may help explain the greater-than-expected benefits of statin therapy in ischemic heart disease.

Enhanced endothelial activation in diabetic patients with unstable angina and non-Q-wave myocardial infarction.

AIMS: Diabetes mellitus (DM) is associated with chronic endothelial dysfunction. Diabetic patients presenting with acute coronary syndromes have a worse prognosis than non-diabetics. An acute inflammatory reaction at the site of coronary plaque rupture and increased expression of surface and soluble cellular adhesion molecules (CAMs) are pathological features of acute coronary syndromes. We set out to characterize the expression of soluble CAMs in patients with and without diabetes presenting with unstable angina (UA) and non Q-wave myocardial infarction (NQMI). METHODS: Patients presenting with UA and NQMI had serum samples taken on presentation, after 72 h and then 3, 6 and 12 months after discharge. Levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin were measured using an ELISA technique. RESULTS: We studied 15 diabetic patients and 15 age- and sex-matched non-diabetic patients presenting with either UA or NQMI. Levels of soluble E-selectin were elevated in the diabetic patients in comparison with the non-diabetic patients at all measured time points: 74 +/- 10 ng/ml vs. 47 +/- 3 ng/ml, P < 0.03 at t = 0 h, 55 +/- 5 ng/ml vs. 38 +/- 2 ng/ml, P < 0.02 at t = 72 h. However, levels of soluble P-selectin were lower in the diabetic cohort during follow-up: 134 +/- 15 ng/ml vs. 225 +/- 32 ng/ml, P < 0.02 at t = 3/12 and 112 +/- 8 ng/ml vs. 197 +/- 23 ng/ml, P < 0.02 at t = 6/12. There was no significant difference in levels of soluble ICAM-1 and VCAM-1 between diabetic and non-diabetic patients. CONCLUSIONS: Levels of soluble E-selectin are significantly elevated in diabetic patients presenting with UA and NQMI in comparison with non-diabetics. This finding may reflect enhanced endothelial activation which may contribute to the adverse prognosis of diabetic patients with acute coronary syndromes.

Six- and ten-item indexes of psychological distress based on the Symptom Checklist-90.

Clinicians, provider organizations, and researchers need simple and valid measures to monitor mental health treatment outcomes. This article describes development of 6- and 10-item indexes of psychological distress based on the Symptom Checklist-90 (SCL-90). A review of eight factor-analytic studies identified SCL-90 items most indicative of overall distress. Convergent validity of two new indexes and the previously developed SCL-10 were compared in an archival sample of posttraumatic stress disorder patients (n = 323). One index, the SCL-6, was further validated with archival data on substance abuse patients (n = 3,014 and n = 316) and hospital staff (n = 542). The three brief indexes had similar convergent validity, correlating .87 to .97 with the SCL-90 and Brief Symptom Inventory, .49 to .76 with other symptom scales, and .46 to .73 with changes in other symptom measures over time. These results indicate the concise, easily administered indexes are valid indicators of psychological distress.

Heart rate during group flooding therapy for PTSD.

The objective of this study was to assess, via heart rate, the arousal levels of participants in group trauma reexposure therapy for posttraumatic stress disorder, and so to better understand this common mode of treatment, particularly in regards to its presumed curative factor, extinction. Six Vietnam combat-related PTSD inpatients participated twice weekly in group trauma reexposure therapy during which their electrocardiograms were recorded. Heart rate was quantified continuously off-line. Heart rates of participants not directly engaged in imaginal reexposure to their personal combat traumas consistently exhibited mild linear declines from the beginnings to the ends of the approximately 2.5 hour sessions. Participants actively engaged in personal combat trauma reexposure exhibited higher whole-session heart rates. Most also exhibited more specific elevation extending over the later portions of therapy sessions during which intensive reexposure usually occurred. Surprisingly, no patients exhibited focal increases in heart rate concurrent with periods of most intensive traumatic incident review as judged from videotape. Administering imaginal reexposure in a group context does not preclude substantial physiological (sympathetic) arousal, as is preconditional for extinction. Under conditions in which the actively engaged reexposure patient is reliably identified, group trauma reexposure therapy may not provide an opportunity for "vicarious" flooding in nonengaged participants.

Characteristics of adolescent psychiatric patients who engage in problematic behavior while intoxicated.

Although many adolescent psychiatric patients drink and use drugs, not all engage in problematic behaviors or experience social difficulties while intoxicated. The goal of this study was to identify characteristics of adolescent psychiatric patients for whom intoxication leads to behavioral, social, and medical problems. Alcohol-involved adolescent psychiatric inpatients were divided into high and low problem severity groups and compared on a number of measures. The groups did not differ in alcohol or drug consumption or psychiatric diagnoses. High problem severity was primarily associated with drinking in response to unpleasant affect and the belief that alcohol enhances social behavior. Explanations for the results are discussed, along with clinical implications.

Incarcerated adolescents' attributions for drug and alcohol use.

Incarcerated adolescents' attributions for drug use were investigated. A new 50-item questionnaire, the Inventory of Drug Taking Situations (IDTS), was used to assess reasons for use. The IDTS yields eight subscales corresponding to risky situations identified by Marlatt and others. On the IDTS, subjects indicate how frequently they used their drug of choice when confronted with each risky situation. The IDTS scales had good internal consistency and higher scores were significantly associated with self-reports of drug use frequency. Furthermore, IDTS scores were most valid for the type of drug the measure was filled out about. Adolescents reported that they tended to use more frequently in response to positive and/or interpersonal experiences, as opposed to negative and/or internal ones. Positive, negative, interpersonal, and internal reasons for use were all equally correlated with frequency of use. In the most heavily drug-involved adolescents, however, negative reasons were more highly correlated with frequency of use than positive reasons. Treatment implications are discussed.

Family dysfunction and alcohol and drug use in adolescent psychiatric inpatients.

This report examines the relationship between family functioning and substance abuse in adolescent psychiatric inpatients. The adolescents, who had been hospitalized after acute psychiatric crises, provided reports of drug and alcohol use, intoxication-related problems, and family functioning during the 4 months preceding hospitalization. Greater degrees of family dysfunction in the areas of affective responsiveness and role functioning were associated with higher levels of substance abuse. When age, sex, and diagnosis were controlled for, family dysfunction in these areas was still significantly associated with alcohol consumption but not with drug use or intoxication-related problems. Implications for treatment are discussed.

School adjustment of children of alcoholic fathers: comparison to normal controls.

The present study used objective indices of academic performance to test the hypothesis that children of alcoholic fathers (COA's) have poorer school adjustment than children of nonalcoholic parents (non-COA's). Subjects were 39 children of male alcoholics treated for alcoholism in a VA program and 33 control children whose nonalcoholic parents (matched on demographic indices) reported low marital conflict. The results showed that daughters of alcoholics, but not the sons, showed more variability than controls in their school attendance. There was suggestive evidence that they also missed more school days than controls, with a reversed pattern for the sons of alcoholics. Generally, however, the COA group was not compromised academically and did not show more conduct problems compared to controls. Within the COA group, long-term paternal drinking adjustment (years of problem drinking and total number of hospitalizations for drinking) appeared to be related to poorer GPA, while short-term adjustment (alcohol-related days in jail and number of days drinking in year previous to treatment) were more related to poorer attendance. The results are discussed in terms of the mechanism of the effect of paternal drinking on children's school adjustment and the difficulty in making generalizations about the consequences of being the child of an alcoholic.