Assessment of eye doses to staff involved in interventional cardiology procedures in Kuwait

In this study, which is the first of its kind in the gulf region, eye doses of interventional cardiologists and nurses were measured using active dosimeters for left and right eyes, in 60 percutaneous coronary interventions in three main hospitals in Kuwait. The dose given in terms of H_p(0.07) per procedure when ceiling suspended screens were used by main operators ranged from 18.5 to 30.3 µSv for the left eye and from 12.6 to 23.6 µSv for the right eye. Taking into account typical staff workload, the results show that the dose limit of 20 mSv/year to the eyes can be exceeded for interventional cardiologists in some situations, which demonstrates the need of using additional effective radiation protection tools, e.g. protective eye spectacles, in addition to the regular and proper use of ceiling suspended screens. With indications of increase in workload, the need for availability of a dedicated active dosimeter for the regular monitoring of eye doses is emphasized.

     

Haloperidol and atypical antipsychotics share a same action of decreasing P75(NTR) mRNA levels in PC12 cells

P75(NTR) is a common neurotrophin receptor which binds all neurotrophins with similar affinities and has been shown to be capable of mediating programmed cell death. In this study, we investigated effects of the antipsychotic drugs (APDs) haloperidol, clozapine, quetiapine, and risperidone on p75(NTR) mRNA levels in PC12 cells. Haloperidol is a prototype of typical APDs, and the other three drugs are atypical APDs, which are effective in reducing negative symptoms and cognitive deficits of schizophrenia, cause less side effects, and are more tolerable compared to haloperidol. PC12 cells were cultured with various concentrations of haloperidol, clozapine, quetiapine, or risperidone, in their media. After culture for 48h, the cell viabilities and p75(NTR) mRNA levels were measured. It was shown that both haloperidol and the atypical APDs used in this study deceased p75(NTR) mRNA levels in PC12 cells in a dose dependent manner, while not affecting cell viabilities. In further experiments, doses that produced significant/greatest effects were chosen and provided in the culture media for various periods. Decreases in p75(NTR) mRNA levels were observed in cultures treated for 12h with quetiapine, 24h with clozapine or risperidone, or for 48h with haloperidol. These results suggest that both haloperidol and atypical APDs have the same action of decreasing p75(NTR) mRNA levels in PC12 cells. Although the underlying molecular mechanism of this action remains to be elucidated, this finding is particularly relevant given the neurodevelopmental deficits associated with schizophrenia and important roles of p75(NTR) in mediating cell death.     

On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis

Parkinson’s disease psychosis (PDP) is a condition that may develop in up to 60 % of Parkinson’s patients, and is a major reason for nursing home placement for those affected. There are no FDA approved drugs for PDP but low doses of atypical anti-psychotic drugs (APDs) are commonly prescribed off-label. Only low-dose clozapine has shown efficacy in randomized controlled trials, but all APDs have black box warnings related to the increased mortality and morbidity when used in elderly demented patients. Using molecular pharmacological profiling of a large collection of marketed drugs, we discovered that potent inverse agonist activity against 5-HT_2A serotonin receptors was a common feature of atypical APDs, especially the atypical APDs used to treat PDP. Since low-dose clozapine therapy selectively blocks this receptor, it was hypothesized that a highly selective 5-HT_2A receptor inverse agonist might provide good symptom control in patients suffering from PDP, with a greatly improved safety and tolerability profile. A high throughput screening and subsequent chemical lead optimization campaign to develop potent, selective 5-HT_2A receptor inverse agonists was launched, eventually resulting in the discovery of pimavanserin. Pimavanserin displays nanomolar potency as a 5-HT_2A receptor inverse agonist, selectivity for 5-HT_2A over 5-HT_2C receptors, and no meaningful activity at any other G-protein coupled receptor. It demonstrated robust activity in preclinical models of schizophrenia and PDP, and did not worsen motoric symptoms, in contrast to the APDs tested. In a Phase III clinical trial, pimavanserin showed highly significant benefits in the primary endpoint, the scale for assessment of positive symptoms-PD, a scale adapted for use in PDP. In addition, improvements in all other efficacy endpoints, including physician’s clinical global impression, caregiver burden, night-time sleep quality and daytime wakefulness, were seen. Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III. An open-label extension study has further demonstrated that pimavanserin is safe and well-tolerated with long-term use. Pimavanserin may therefore offer a viable treatment option for patients suffering from PDP.     

Patient and staff doses in paediatric interventional cardiology derived from experimental measurements with phantoms

The aim of this paper was to determine experimentally the entrance surface air kerma (ESAK) and kerma-area product (KAP) levels to patients and scatter doses at the cardiologist's eyes during paediatric interventional cardiology (IC) procedures for Chile, on the basis of measurements taken from X-ray systems characterization for different thicknesses of polymethyl methacrylate, together with the average values of fluoroscopy time and number of cine frames for ten paediatric IC procedures. The range of cumulative ESAK values when the different clinical procedures were simulated was from 2 to 1100 mGy. KAP values ranged from 0.30 to 150 Gy cm². Scatter doses at cardiologist's eyes for the simulated procedures ranged from 0.20 to 116 µSv per procedure. Large differences between the X-ray systems were found in our study. Standardized guidelines in terms of X-ray system setting and protocols should be developed for hospitals that perform paediatric IC procedures in Chile.     

Validation of the MC-GPU Monte Carlo code against the PENELOPE/penEasy code system and benchmarking against experimental conditions for typical radiation qualities and setups in interventional radiology and cardiology

IntroductionInterventional procedures are associated with potentially high radiation doses to the skin. The 2013/59/EURATOM Directive establishes that the equipment used for interventional radiology must have a device or a feature informing the practitioner of relevant parameters for assessing patient dose at the end of the procedure. Monte Carlo codes of radiation transport are considered to be one of the most reliable tools available to assess doses. However, they are usually too time consuming for use in clinical practice. This work presents the validation of the fast Monte Carlo code MC-GPU for application in interventional radiology.MethodologiesMC-GPU calculations were compared against the well-validated Monte Carlo simulation code PENELOPE/penEasy by simulating the organ dose distribution in a voxelized anthropomorphic phantom. In a second phase, the code was compared against thermoluminescent measurements performed on slab phantoms, both in a calibration laboratory and at a hospital.ResultsThe results obtained from the two simulation codes show very good agreement, differences in the output were within 1%, whereas the calculation time on the MC-GPU was 2500 times shorter. Comparison with measurements is of the order of 10%, within the associated uncertainty.ConclusionsIt has been verified that MC-GPU provides good estimates of the dose when compared to PENELOPE program. It is also shown that it presents very good performance when assessing organ doses in very short times, less than one minute, in real clinical set-ups. Future steps would be to simulate complex procedures with several projections.     

A twin study of auditory processing indicates that dichotic listening ability is a strongly heritable trait

We administered tests commonly used in the diagnosis of auditory processing disorders (APDs) to twins recruited from the general population. We observed significant correlations in test scores between co-twins. Our analyses of test score correlations among 106 MZ and 33 DZ twin pairs indicate that dichotic listening ability is a highly heritable trait. Dichotic listening is the ability to identify and distinguish different stimuli presented simultaneously to each ear. Deficits in dichotic listening skills indicate a lesion or defect in interhemispheric information processing. Such defects or lesions can be prominent in elderly listeners, language-impaired children, stroke victims, and individuals with PAX6 mutations. Our data indicates that other auditory processing abilities are influenced by shared environment. These findings should help illuminate the etiology of APDs, and help to clarify the relationships between auditory processing abilities and learning/language disorders associated with APDs. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Estimating HIV Incidence Based on Combined Prevalence Testing

Summary .  Knowledge of incidence rates of HIV and other infectious diseases is important in evaluating the state of an epidemic as well as for designing interventional studies. Estimation of disease incidence from longitudinal studies can be expensive and time consuming. Alternatively, Janssen et al. (1998,  Journal of the American Medical Association   280, 42–48) proposed the estimation of HIV incidence at a single point in time based on the combined use of a standard and "detuned" antibody assay. This article frames the problem from a longitudinal perspective, from which the maximum likelihood estimator of incidence is determined and compared with the Janssen estimator. The formulation also allows estimation for general situations, including different batteries of tests among subjects, inclusion of covariates, and a comparative evaluation of different test batteries to help guide study design. The methods are illustrated with data from an HIV interventional trial and a seroprevalence survey recently conducted in Botswana.     

Modeling ventricular repolarization: effects of transmural and apex-to-base heterogeneities in action potential durations

Heterogeneities in the densities of membrane ionic currents of myocytes cause regional variations in action potential duration (APD) at various intramural depths and along the apico-basal and circumferential directions in the left ventricle. This work extends our previous study of cartesian slabs to ventricular walls shaped as an ellipsoidal volume and including both transmural and apex-to-base APD heterogeneities. Our 3D simulation study investigates the combined effect on repolarization sequences and APD distributions of: (a) the intrinsic APD heterogeneity across the wall and along the apex-to-base direction, and (b) the electrotonic currents that modulate the APDs when myocytes are embedded in a ventricular wall with fiber rotation and orthotropic anisotropy. Our findings show that: (i) the transmural and apex-to-base heterogeneities have only a weak influence on the repolarization patterns on myocardial layers parallel to the epicardium; (ii) the patterns of APD distribution on the epicardial surface are mostly affected by the apex-to-base heterogeneities and do not reveal the APD transmural heterogeneity; (iii) the transmural heterogeneity is clearly discernible in both repolarization and APD patterns only on transmural sections; (iv) the apex-to-base heterogeneity is clearly discernible only in APD patterns on layers parallel to the epicardium. Thus, in our orthotropic ellipsoidal wall, the complex 3D electrotonic modulation of APDs does not fully mix the effects of the transmural and apex-to-base heterogeneity. The intrinsic spatial heterogeneity of the APDs is unmasked in the modulated APD patterns only in the appropriate transmural or intramural sections. These findings are independent of the stimulus location (epicardial, endocardial) and of Purkinje involvement.     

Absorbed dose in the operator’s brain in interventional radiology practices: evaluation through KAP value conversion factors

In order to address the recent concerns over a possible increasing in brain tumour mortality among interventional radiologists and cardiologist, this work evaluated the exposure conditions of the operator’s brain during interventional procedures using Monte Carlo simulations with anthropomorphic phantoms. The absorbed doses in several predefined segments of the operator’s brain were estimated in a typical interventional radiology irradiation scenario. The doses were normalized to the KAP values simulated for ten X-ray beam qualities and four projections (PA, RAO 25°, LAO 25° and CRA 25°). For the interventional radiology scenario, because of the position of the operator, no difference was found in the exposure between the left and right regions of the brain for the first operator. However, for the second operator standing at a farer distance from the tube, the exposure of the left part of the brain is up to two times higher than that of the right part. The results are in agreement with dose measurements reported in the literature. The conversion factors, obtained as the absorbed dose per KAP, can be used to obtain a first estimate of the exposure of the brain of the operators during interventional procedures.     

Fast Monte Carlo codes for occupational dosimetry in interventional radiology

PurposeInterventional radiology techniques cause radiation exposure both to patient and personnel. The radiation dose to the operator is usually measured with dosimeters located at specific points above or below the lead aprons. The aim of this study is to develop and validate two fast Monte Carlo (MC) codes for radiation transport in order to improve the assessment of individual doses in interventional radiology. The proposed methodology reduces the number of required dosemeters and provides immediate dose results.MethodsTwo fast MC simulation codes, PENELOPE/penEasyIR and MCGPU-IR, have been developed. Both codes have been validated by comparing fast MC calculations with the multipurpose PENELOPE MC code and with measurements during a realistic interventional procedure.ResultsThe new codes were tested with a computation time of about 120 s to estimate operator doses while a standard simulation needs several days to obtain similar uncertainties. When compared with the standard calculation in simple set-ups, MCGPU-IR tends to underestimate doses (up to 5%), while PENELOPE/penEasyIR overestimates them (up to 18%). When comparing both fast MC codes with experimental values in realistic set-ups, differences are within 25%. These differences are within accepted uncertainties in individual monitoring.ConclusionThe study highlights the fact that computational dosimetry based on the use of fast MC codes can provide good estimates of the personal dose equivalent and overcome some of the limitations of occupational monitoring in interventional radiology. Notably, MCGPU-IR calculates both organ doses and effective dose, providing a better estimate of radiation risk.     

Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: I. Without exogenous activation

There has been an increasing need in genetic toxicology to progress from strictly qualitative tests to more quantitative tests. This, in turn, has increased the need to develop better quality assurance and comparative bioassay methods. In this paper, two laboratories tested 10 Salmonella mutagens in order to determine the usefulness of selected chemicals as potential reference materials to calibrate the Salmonella assay. If variance within a bioassay is sufficiently low and the rankings of the compounds are of acceptable consistency, the chemicals later could be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The results demonstrated that the chosen chemicals (with the possible exception of dimethylcarbamylchloride) provide such consistent results in the Salmonella mutagenicity bioassay that they can be used for semi-quantitative calibration and as possible bioassay controls, special audit chemicals, and potentially as reference standards in comparative bioassay efforts. Reference standards, whether used as audit materials or in comparative bioassays, must be used concurrently with the test substances of interest; used without bias; used in a standardized, highly controlled bioassay; and be tested across an appropriate dose range. The study also shows that when these compounds are used as reference standards much care must be given to the number and spacing of doses if highly reproducible slope values are to be generated. We recommend use of a pilot test to establish a dose range for definitive tests and the placement of doses for the definitive tests within the first half of the linear dose-response curve. For appropriate comparisons, one should replicate the tests using the defined dose range and analyze the results in a non-biased statistical manner.     

Reductive stress on life span extension in C. elegans

Background

Induction programme for trainee doctors in the UK generally do not focus on the surgical aspects of their jobs. In this context we decided to conduct a telephonic survey among the hospitals belonging to three orthopaedic training regions in the UK from the point of view of the diversity of instrumentations and implants used for index procedures.

Results

We chose four index trauma & orthopaedic procedures (Total hip replacement, total knee replacement, intramedullary nailing and external fixator systems for long bone fractures). A telephonic survey was done in six NHS trust hospitals which were part of an orthopaedic training rotation (2 from England, 2 from Wales and 2 from Scotland). In total there were 39 different instrumentation systems for these 4 index procedures in the 6 trusts (see table 1). These comprise 12 Total hip replacement (THR) systems, 14 total knee replacement (TKR) systems, 9 intra-medullary nailing systems, and 4 external fixator systems. The number of different systems for each trust ranged from 7 to 19. There is a vast array of implants and instrumentation systems in each trust, as highlighted by our survey. The surgical tools are not the same in each hospitals. This situation is more complicated when trainees move to new hospitals as part of training rotations.

Multiple hypothesis testing in proteomics: a strategy for experimental work

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis. We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.     

Updating national diagnostic reference levels for interventional cardiology and methodological aspects

The aim of this study is to propose national diagnostic reference levels (DRL) for updating in the field of interventional cardiology and to include technical details to help plan optimization.Medical physics experts and interventional cardiologists from 14 hospitals provided patient dose indicators from coronary angiography and percutaneous coronary interventions. Information about X-ray system dose settings and image quality was also provided.The dose values from 30,024 procedures and 26 interventional laboratories were recorded. The national DRLs proposed for coronary angiography and percutaneous coronary interventions were respectively 39 and 78 Gy·cm² for air kerma area product (P_KA), 530 and 1300 mGy for air kerma at reference point (K_a,r), 6.7 and 15 min of fluoroscopy time and 760 and 1300 cine images. 36% of the KAP meters required correction factors from 10 to 35%. The dose management systems should allow these corrections to be included automatically. The dose per image in cine in reference conditions differed in a factor of 5.5.Including X-ray system dose settings in the methodology provides an insight into the differences between hospitals. The DRLs proposed for Spain in this work were similar to those proposed in the last European survey. The poor correlation between X-ray systems dose settings and patient dose indicators highlights that other factors such as operation protocols and complexity may have more impact in patient dose indicators, which allows a wide margin for optimization. Dose reduction technology together with appropriate training programs will be determinant in the future reduction of patient dose indicators.     

Use of a Heart Team in Decision-Making for Patients with Complex Coronary Disease at Hospitals in Michigan Prior to Guideline Endorsement

Background

Revascularization decisions can profoundly impact patient survival, quality of life, and procedural risk. Although use of Heart Teams to make revascularization decisions is growing, data on their implementation in the real-world are limited. Our objective was to assess the prevalence of Heart Teams and their association with collaboration in routine practice.

Methods

A survey of cardiologists and cardiac surgeons at 31 hospitals in Michigan was performed in May, 2011 – prior to the recommendation for using Heart Teams in national guidelines. This survey included all percutaneous coronary intervention-performing hospitals in Michigan participating in the Blue Cross/Blue Shield of Michigan Cardiovascular Consortium and Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. It targeted both the use of Heart Teams and multidisciplinary Case Conferences.

Results

There were 53 physician survey respondents from 27 hospitals with 4 hospitals not responding. Among respondents, 11 (40.7%) hospitals reported no Heart Teams or Case Conferences while 7 (25.9%) hospitals reported either a Heart Team or Case Conference. However, there was disagreement about the presence of a Heart Team at seven hospitals, and about Case Conferences at nine hospitals. Hospitals with definite Heart Teams reported significantly greater levels of collaboration between cardiologists and cardiac surgeons.

Conclusion

The overall presence of Heart Teams prior to their recommendation in national guidelines was limited. Even among hospitals with a potential Heart Team, there was substantial disagreement between respondents about their presence. Further refinement of the definition of a Heart Team and measures of successful implementation are needed.     

Antimicrobial drug use in three Canadian general hospitals.

Total amounts of antimicrobial drugs used to treat inpatients during 1975 were calculated for three Canadian general hospitals, one of them the principal teaching hospital of a medical school. Use of drugs was compared with that reported for Boston City Hospital during periods when antimicrobial therapy was and was not supervised by infectious disease consultants. Ampicillin, tetracyclines, cephalosporins, erythromycin and aminoglycosides for prophylactic oral administration were used excessively in the three hospitals. The degree of overuse was comparable to that at Boston City Hospital during years when drug use was uncontrolled. Overuse or improper choice of antimicrobial drug decreases the quality of patient care and increases its cost. More rigorous education is needed for both medical students and practising physicians in the rational use of antimicrobial drugs. Informal consultation with an infectious disease unit should be required before certain overly popular or toxic antibiotics are administered to hospitalized patients.     

How tumor markers are used in the routine follow-up of breast and colorectal cancer. A survey of 29 Italian hospitals

The impact of tumor markers on the outcome of several malignancies is still under debate. This relative uncertainty leads to a subjective approach to their use. Monitoring the use of tumor markers is a valuable tool to identify the need for educational policies. We conducted a survey to evaluate how tumor markers are routinely used in the follow-up of patients with breast, colorectal and ovarian carcinoma. The former two malignancies are considered in the present paper. We surveyed 35 Italian hospitals; 29 (83%, accounting for 26,622 hospital beds) filled in and returned the questionnaire. Overall, 467,361 tumor marker requests were scrutinized by the surveyed hospitals. We found a wide variability in the type and number of routinely used markers, the cutoff points chosen, and the clinical decisions taken on the basis of marker results. In addition, we observed a relative lack of communication between clinicians and clinical pathologists in around 50% of the surveyed hospitals. In these cases clinical information was not provided to the laboratory and methodological aspects were not communicated to clinicians. From the findings of the present study we conclude that the cooperation between clinicians and clinical pathologists must improve before guidelines for the use of tumor marker assays can be framed and the compliance with these guidelines can be checked. Request forms for tumor marker assays should therefore be designed to contain clinical information and the quality of filling in request forms with clinical data should be carefully monitored.     

Radioprotection of eye lens using protective material in neuro cone-beam computed tomography: Estimation of dose reduction rate and image quality

PurposeIn cerebral angiography, for diagnosis and interventional neuroradiology, cone-beam computed tomography (CBCT) scan is frequently performed for evaluating brain parenchyma, cerebral hemorrhage, and cerebral infarction. However, the patient’s eye lens is more frequently exposed to excessive doses in these scans than in the previous angiography and interventional neuroradiology (INR) procedures. Hence, radioprotection for the lenses is needed. This study selects the most suitable eye lens protection material for CBCT from among nine materials by evaluating the dose reduction rate and image quality.MethodsTo determine the dose reduction rate, the lens doses were measured using an anthropomorphic head phantom and a real-time dosimeter. For image quality assessment, the artifact index was calculated based on the pixel value and image noise within various regions of interest in a water phantom.ResultsThe protective materials exhibited dose reduction; however, streak artifacts were observed near the materials. The dose reduction rate and the degree of the artifact varied significantly depending on the protective material. The dose reduction rates were 14.6%, 14.2%, and 26.0% when bismuth shield: normal (bismuth shield in the shape of an eye mask), bismuth shield: separate (two separate bismuth shields), and lead goggles were used, respectively. The “separate” bismuth shield was found to be effective in dose reduction without lowering the image quality.ConclusionWe found that bismuth shields and lead goggles are suitable protective devices for the optimal reduction of lens doses.     

Obstetric Anaesthesia Services in the United Kingdom

In a survey of obstetric anaesthetic services in the United Kingdom questionnaires were sent to 398 hospital maternity units and 347 general-practitioner maternity units, of which 344 and 272 respectively were returned. Many hospitals were unable to provide an anaesthetist for obstetric surgery only, and few consultant anaesthetist sessions were allocated to obstetric surgery, particularly in regional hospitals in England and Wales. Constant supervision of junior anaesthetic staff with under 12 months'' experience was lacking in several hospitals. Endotracheal intubation is widely used throughout the United Kingdom. Though regional analgesic techniques are used by most anaesthetists it is impossible to provide a 24-hour regional analgesic service in all but a few hospitals.