Size based dependence of patient dose metrics, and image quality metrics for clinical indicator-based imaging protocols in abdominal CT procedures.

INTRODUCTION: Diagnostic reference level (DRL) values for computed tomography (CT) based on clinical indication are warranted since imaging protocols are indication-dependent. This study proposes clinical DRL values using the CT dose metrics and five patient size-related parameters while considering image quality. METHODS: The volumetric CT dose index (CTDIvol), dose-length product (DLP) and five size-related parameters of size-specific dose estimates (SSDE), namely the anterior-posterior (AP) dimension, lateral (LAT) dimension, sum dimension, effective diameter, and the body mass index (BMI), were used to calculate DRL values for CT chest-abdomen-pelvis (CAP) and abdomen-pelvis (AbP) protocols. DRL values of the clinical indications for cancer, urinary system stones and other pathologies were assessed based on the BMI classifications using the median and 75th percentile. An image subtraction algorithm was used to assess the image quality metrics (IQM) of the CT images. RESULTS: The 75th percentile for SSDEAP dimension for CAP cancer was 19.7, 14.9 and 12.7 mGy at Hospitals A, C and E, respectively. The median DLP for other AbP pathologies was 556.3, 1452.0 and 1960.7 mGy.cm for normal weight, overweight and obese patients, respectively, at Hospital A. The image quality varied among BMI classifications for different clinically indicated examinations. Although the dose increased with BMI, the image quality index was consistent because automatic tube current modulation (ATCM) was used. CONCLUSION: DRL values are influenced by patient size-related parameters and the clinical indication protocols, while the image quality index is independent of the BMI. IMPLICATIONS FOR PRACTICE: Size-related clinical DRL values and image quality index can be used to monitor and optimise dose and image quality. Acquisition parameters and image quality indexes should be investigated and adjusted when unusually high DRL values are noted.

Breast cancer detection: Comparison of digital mammography and digital breast tomosynthesis across non-dense and dense breasts.

INTRODUCTION: Breast density is associated with an increase in breast cancer risk and limits early detection of the disease. This study assesses the diagnostic performance of mammogram readers in digital mammography (DM) and digital breast tomosynthesis (DBT). METHODS: Eleven breast readers with 1-39 years of experience reading mammograms and 0-4 years of experience reading DBT participated in the study. All readers independently interpreted 60 DM cases (40 normal/20 abnormal) and 35 DBT cases (20 normal/15 abnormal). Sensitivity, specificity, ROC AUC, and diagnostic confidence were calculated and compared between DM and DBT. RESULTS: DBT significantly improved diagnostic confidence in both dense breasts (p = 0.03) and non-dense breasts (p = 0.003) but not in other diagnostic performance metrics. Specificity was higher in DM for readers with >7 years' experience (p = 0.03) in reading mammography, non-radiologists (p = 0.04), readers who had completed a 3-6 months training fellowship in breast imaging (p = 0.04), and those with ≤2 years' experience in reading DBT (p = 0.02), particularly in non-dense breasts. CONCLUSION: Diagnostic confidence was higher in DBT when compared to DM. In contrast, other performance metrics appeared to be similar or better with DM and may be influenced by the lack of experience of the reader cohort in reading DBT. IMPLICATIONS FOR PRACTICE: The benefits of DBT may not be entirely accrued until radiologists attain expertise in DBT interpretation. Specificity of DBT varied according to reader characteristics, and these characteristics may be useful for optimising pairing strategies in independent double reading of DBT as practiced in Australia to reduce false positive diagnostic errors.

Features and roles of T helper 9 cells and interleukin 9 in immunological diseases

T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention

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Features and roles of T helper 9 cells and interleukin 9 in immunological diseases.

T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention.

Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics.

Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next-generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty-seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.

A multiple methods approach: radiation associated cataracts and occupational radiation safety practices in interventionalists in South Africa.

Ionising radiation is a modality used in diagnostic and therapeutic medicine. The technology has improved and resulted in lower dose exposure but there has been an escalation in the quantity of procedures, their duration and complexity. These factors have meant increased occupational radiation exposure for interventionalists. Ionising radiation exposure can have detrimental health effects and includes radiation skin burns, various carcinomas, genetic and chromosomal aberrations and cataractogenesis of the lenses of the eye. The lenses of the eye are of the most radiosensitive organs and the risk of cataracts is high despite low radiation dose exposures. The use of personal protective equipment (PPE) is a method that can be used to mitigate the risk for developing lens opacifications. The consistent and effective utilisation of PPE is marred by availability, proper fit and ease of use when performing procedures. Radiation safety training is imperative to enforce a culture of radiation safety among interventionalists. The aim of this study was to quantify and describe cataracts among South African interventionalists and to understand their radiation safety practices. For this purpose, a cross sectional study was designed using multiple methods. A survey was conducted to determine the demographics and the risk factors of doctors exposed to radiation to doctors not exposed. The radiation workload and radiation safety practices of interventionalists were explored. Both groups had slit lamp examinations. The data were analysed analytically and a regression model developed looking at the outcomes and the risk factors. Qualitative in-depth interviews and group interviews were conducted to explore the perceptions of interventionalists regarding radiation safety. Deductive and inductive thematic analysis was done. Interdisciplinary research is challenging but offers tremendous opportunity for exploring and tackling complex issues related to securing a safe radiation work environment.

Perceptions of radiation safety training among interventionalists in South Africa

Exposure to ionising radiation may have deterministic and stochastic health effects, which include skin changes, chromosomal aberrations, cataracts and carcinomas. Formalised training in radiation safety and protection improves knowledge on the subject and facilitates greater compliance in safety practices. This qualitative study included 54 interventionalists (adult and paediatric cardiologists, and interventional radiologists). The participants were purposively selected and interviewed to explore their perceptions about radiation safety. A thematic analysis of the transcripts was done using a deductive and inductive approach. Findings showed participating cardiologists had less knowledge about radiation safety than participating radiologists. Cardiologists reported little or no formal training on radiation safety and did not display a culture of radiation safety. There was no consensus on how the training gap should be addressed. There is a perceived need to change and enhance the radiation safety culture among interventionists, and the participants proffered some ideas. These included the need for re-curricularisation of cardiologists' training to create awareness of radiation safety practices

Dependence of Shape-Based Descriptors and Mass Segmentation Areas on Initial Contour Placement Using the Chan-Vese Method on Digital Mammograms.

Variation in signal intensity within mass lesions and missing boundary information are intensity inhomogeneities inherent in digital mammograms. These inhomogeneities render the performance of a deformable contour susceptible to the location of its initial position and may lead to poor segmentation results for these images. We investigate the dependence of shape-based descriptors and mass segmentation areas on initial contour placement with the Chan-Vese segmentation method and compare these results to the active contours with selective local or global segmentation model. For each mass lesion, final contours were obtained by propagation of a proposed initial level set contour and by propagation of a manually drawn contour enclosing the region of interest. Differences in shape-based descriptors were quantified using absolute percentage differences, Euclidean distances, and Bland-Altman analysis. Segmented areas were evaluated with the area overlap measure. Differences were dependent upon the characteristics of the mass margins. Boundary moments presented large percentage differences. Pearson correlation analysis showed statistically significant correlations between shape-based descriptors from both initial locations. In conclusion, boundary moments of digital mass lesions are sensitive to the placement of initial level set contours while shape-based descriptors such as Fourier descriptors, shape convexity, and shape rectangularity exhibit a certain degree of robustness to changes in the location of the initial level set contours for both segmentation algorithms.

A Randomized Trial of a Bereavement Intervention for Pregnancy Loss.

OBJECTIVE: To examine the effects of a secondary bereavement intervention on grieving in women who experienced a miscarriage (pregnancy loss) at 12-20 weeks gestation. DESIGN: Experimental, posttest only, control group design. SETTING: Obstetric emergency center of a county hospital in a large city. PARTICIPANTS: Forty women who experienced complete spontaneous miscarriages in the first or second trimester (8-20 weeks gestation). METHODS: Participants were randomly assigned to the grief intervention treatment group or usual standard care control group. The Medical Professional Guidelines for Health Care Professionals were used to construct the perinatal grief intervention. The Perinatal Grief Scale (PGS) was completed during a routine follow-up visit 2 weeks postloss. RESULTS: A one-way multiple ANOVA (MANOVA) was used to examine the difference in grieving between the control and experimental groups. Three dependent variables were used: despair, difficulty coping, and active grieving. Analysis revealed a significant difference on the combined dependent variables, F(3, 36) = 22.40, p < .000. When considering the three dependent variables separately, the treatment group displayed significantly lower levels of despair, F(1, 38) = 42.27, p < .001. Active grieving was high in both groups with the treatment group mean higher than the control group. Group means were similar for coping difficulty. CONCLUSION: A bereavement intervention administered immediately after the miscarriage promotes women's ability to cope with early pregnancy loss.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Commercial air travel and in-flight pulmonary hypertension.

BACKGROUND: It has recently been shown that commercial air travel triggers hypoxic pulmonary vasoconstriction and modestly increases pulmonary artery pressure in healthy passengers. There is large interindividual variation in hypoxic pulmonary vasoreactivity, and some passengers may be at risk of developing flight-induced pulmonary hypertension, with potentially dangerous consequences. This study sought to determine whether it is possible for a susceptible passenger to develop pulmonary hypertension in response to a routine commercial flight. CASE REPORT: Using in-flight echocardiography, a passenger was studied during a 6-h commercial flight from London to Dubai. The passenger was generally well and frequently traveled by air, but had been diagnosed with Chuvash polycythemia, a genetic condition that is associated with increased hypoxic pulmonary vasoreactivity. Hematocrit had been normalized with regular venesection. During the flight, arterial oxygen saturation fell to a minimum of 96% and systolic pulmonary artery pressure (sPAP) rapidly increased into the pulmonary hypertensive range. The in-flight increase in sPAP was 50%, reaching a peak of 45 mmHg. DISCUSSION: This study has established that an asymptomatic but susceptible passenger can rapidly develop in-flight pulmonary hypertension even during a medium-haul flight. Prospective passengers at risk from such responses, including those who have cardiopulmonary disease or increased hypoxic pulmonary vasoreactivity, could benefit from preflight evaluation with a hypoxia altitude simulation test combined with simultaneous echocardiography (HAST-echo). The use of in-flight supplementary oxygen should be considered for susceptible individuals, including all patients diagnosed with Chuvash polycythemia.

Pulmonary artery pressure increases during commercial air travel in healthy passengers.

BACKGROUND: It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. METHODS: Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. RESULTS: Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. CONCLUSIONS: Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients.

Evaluation of an uncollimated printed paper transmission source used under scatter limiting conditions.

Transmission sources used for image attenuation correction, allowing image quantification, are collimated to reduce scatter. We propose the same effect can be achieved for an uncollimated source by increasing source to patient distance. The aim was to compare planar image performance characteristics and absorbed doses of uncollimated and collimated radioactive printed paper transmission sources. The scatter contribution to the uncollimated (99m)Tc source data was evaluated for different combinations of detector phantom distance, detector source distance and phantom source distance. Measurements were performed by increasing the Lucite phantom thickness in 1cm steps to 20 cm. Spatial resolution, detection efficiency and entrance absorbed dose rate were measured for the uncollimated and collimated transmission source images. Results derived from the energy spectra, obtained with the uncollimated transmission source indicate that scatter contribution increases with decreasing detector source distance. The scatter component in the uncollimated transmission images (detector source distances ≥ 60 cm; phantom source distances ≥ 40 cm) was comparable to that obtained with collimated transmission images. Attenuation coefficients obtained compared well (0.168 cm⁻¹ vs. 0.171 cm⁻¹). The full widths at half maxima differed by less than 0.9 mm. The detection efficiency of the uncollimated source was 2.5 times higher than obtained with the collimated source. The entrance absorbed dose obtained from an uncollimated source was 3.75 times larger than that obtained from the collimated source. An uncollimated transmission source (detector source distance ≥ 60 cm) results in acceptable image characteristics and presents a low cost, low dose, high efficiency option for transmission imaging.

Defragmenting care: testing an intervention to increase the effectiveness of interdisciplinary health care teams.

Few studies in the literature have examined the outcomes of health care interdisciplinary teams. Most existing studies have measured attributes of health care teams; however, none have implemented and examined outcomes of a team development intervention. This study was conducted to determine whether a development intervention used with an existing interdisciplinary team would reduce the length of stay for patients in an acute care setting. A quasi-experimental single-subject time series design was conducted with multiple measures of length of stay collected across baseline, intervention, and reversal phases of the study. Bronstein's Model for Interdisciplinary Collaboration provided the framework for this study. The components of this model were used to guide a team development intervention comprised of 4 consecutive weeks of classroom development sessions and 4 consecutive weeks of booster messaging. Length of stay (LOS) data were collected for each of the study phases to examine preintervention LOS and compare these data with LOS during the intervention and reversal phases. The results of this study revealed that the interdisciplinary team development intervention had no positive effect on the length of stay data. Baseline mean LOS across 12 baseline months was 4.83 days (SD=0.65) with monthly means ranging from 4.1 to 6.3 days. The mean LOS was 5.1 and 4.6 days for the intervention months of May and June and 6.0, 6.5, 5.7, and 5.4 days for the reversal months of July to October, respectively. All means in the intervention and reversal phases were higher than comparable months in the baseline phase. The pattern of the graphed trend was closely aligned with the seasonal variations seen during the baseline months. Although these results showed that the team development intervention provided for this interdisciplinary team had no positive effect on the LOS, there are many factors that may have influenced the results and may provide insights useful for future research. LOS may not be the outcome variable that reflects team effectiveness for this population. It is possible that the interdisciplinary team in this study had well-developed collaborative processes before the intervention. Physicians were not included in the team development intervention yet may be the discipline whose participation may have affected LOS.

Proof of life: a protocol for pregnant women who experience pre-20-week perinatal loss.

One in 6 pregnancies is lost before the 20th week of gestation and the psychological impacts of this loss are frequently unaddressed while attention is focused on immediate physiological needs. To improve the comprehensive care provided to women experiencing pre-20-week loss, an evidence-based intervention protocol was developed to provide emotional support to these women in the immediate aftermath of the loss. The protocol was tested using a sample of 40 women who experienced a pre-20-week perinatal loss and were being treated in a large county emergency center. Twenty randomly selected women received the intervention protocol while another 20 women received the usual standard of care. Both groups completed the Perinatal Grief Scale during a routine 2-week follow-up visit. The results indicated that the intervention was effective in ameliorating the degree of despair in women experiencing an early pregnancy loss. Women receiving the protocol expressed feelings of being supported and cared for by the staff. Secondary benefits were an increased collaboration among health care professionals, development of an environment of empathy, and a change in the culture of belief that these women needed only physical care. Results indicate a need for a support protocol for all women experiencing loss regardless of gestational age.

Reducing the failure risk of interdisciplinary healthcare teams.

Interdisciplinary healthcare teams have become the new model for patient care delivery in today's complex healthcare environment of increased specialization and disciplinarity of healthcare providers. Research to support the efficacy of this model has been problematic because of poorly conceptualized interdisciplinary teams as well as methodological problems conducting the research. Findings from organizational studies and healthcare interdisciplinary research can be integrated into a theory-based model to design an educational workshop to develop team members. Development of team members is proposed as a means to enhance collaboration among team members and therefore reduce the risk of team failure.

Identification of the breast edge using areas enclosed by iso-intensity contours.

The segmentation of a mammogram into background and breast is a crucial first step in the computer aided diagnosis of mammograms that has the advantage of simplifying further processing of the image (by eliminating the background) and also provides a reference for the alignment of views when two views are being compared. A novel method of segmenting the breast from the background by analysing the area enclosed by iso-intensity contours is presented. Results are evaluated by comparison with manual borders drawn by three radiologists for a set of 25 mammograms. The effect of different pre-processing methods, on the accuracy of automated borders, is investigated. The best methods yielded average root-mean-square differences between the manual and automated iso-intensity borders of 3.0+/-0.3 mm for the image set containing clear breast edges and 4.8+/-0.5 mm for the image set containing indistinct breast edges compared to 5.1+/-0.8 and 7.9+/-0.9 mm for the two data sets with no pre-processing. Results are also compared to those obtained from global thresholding.

The effects of oral versus written instructions on parents' recall and satisfaction after pediatric appointments.

This study explored the differential effects of written versus oral instructions on parents' recall of information and satisfaction after pediatric appointments. Ninety-six parents completed descriptive information and satisfaction ratings, and four pediatricians completed ratings concerning the complexity level of the appointment. After the appointment, parents were randomly assigned to the Written condition (to receive a transcription of the pediatrician's instructions) or Oral condition (verbal instruction only). Parents were telephoned 5 to 7 days later to report their recall of instructions and satisfaction with the appointment. For the Oral condition parents only, more previous appointments with a given pediatrician were associated with greater parental satisfaction and recall of instructions, and more previous appointments and more time spent with the pediatrician were related to fewer forgotten instructions. Parental characteristics, such as age, number of children, and occupational status, were associated with satisfaction and accurate recall. Implications of these findings are discussed.