Pharyngeal Constrictor Dose-Volume Histogram Metrics and Patient-Reported Dysphagia in Head and Neck Radiotherapy.

AIMS: Head and neck radiotherapy long-term survival continues to improve and the management of long-term side-effects is moving to the forefront of patient care. Dysphagia is associated with dose to the pharyngeal constrictors and can be measured using patient-reported outcomes to evaluate its effect on quality of life. The aim of the present study was to relate pharyngeal constrictor dose-volume parameters with patient-reported outcomes to identify prognostic dose constraints. MATERIALS AND METHODS: A 64-patient training cohort and a 24-patient testing cohort of oropharynx and nasopharynx cancer patients treated with curative-intent chemoradiotherapy were retrospectively examined. These patients completed the MD Anderson Dysphagia Inventory outcome survey at 12 months post-radiotherapy to evaluate late dysphagia: a composite score lower than 60 indicated dysphagia. The pharyngeal constrictor muscles were subdivided into four substructures: superior, middle, inferior and cricopharyngeal. Dose-volume histogram (DVH) metrics for each of the structure combinations were extracted. A decision tree classifier was run for each DVH metric to identify dose constraints optimising the accuracy and sensitivity of the cohort. A 60% accuracy threshold and feature selection method were used to ensure statistically significant DVH metrics were identified. These dose constraints were then validated on the 24-patient testing cohort. RESULTS: Existing literature dose constraints only had two dose constraints performing above 60% accuracy and sensitivity when evaluated on our training cohort. We identified two well-performing dose constraints: the pharyngeal constrictor muscle D63% < 55 Gy and the superior-middle pharyngeal constrictor combination structure V31Gy < 100%. Both dose constraints resulted in ≥73% mean accuracy and ≥80% mean sensitivity on the training and testing patient cohorts. In addition, a pharyngeal constrictor muscle mean dose <57 Gy resulted in a mean accuracy ≥74% and mean sensitivity ≥60%. CONCLUSION: Mid-dose pharyngeal constrictor muscle and substructure combination dose constraints should be used in the treatment planning process to reduce late patient-reported dysphagia.

Can We Miniaturize CT Technology for a Successful Mobile Stroke Unit Roll-Out?

Mortality from stroke remains high in Australia, especially for patients located outside the metropolitan cities. This is because they have limited access to specialized stroke facilities for optimal stroke treatment. Mobile stroke units have the capability to take CT scanners out to the patient however current CT commercial scanner designs are large and heavy. As such, this paper aims to design and develop a lightweight CT scanner for use in a mobile stroke unit (either road-based or air-based ambulance) to bring healthcare solution to patients in the rural and remote areas. We used the engineering design optimization approach to redesign and reduce the weight of the existing CT scanner with without compromised it structural performance. We managed to reduce the weight the CT scanner by three-fold while reducing design costs by allowing numerous simulations to be performed using computer software to achieve our design goals. The results are not only useful to optimize CT scanner structure to retrofit on a mobile stroke unit, but also bring the medical device solution to the market and support scalable solution to the larger community. Such an advance will allow for improved equity in healthcare whereby patients can be treated irrespective of location.

Cross-sectional study to assess the psychological morbidity of women facing possible miscarriage.

INTRODUCTION: Threatened miscarriage is a common complication of pregnancy. This study aimed to assess psychological morbidity in women with threatened miscarriage, with the goal of identifying early interventions for women at risk of anxiety or depression. METHODS: Women in their first trimester attending an Early Pregnancy Assessment Clinic were recruited between July 2013 and June 2015. They were asked to complete the 12-item General Health Questionnaire (GHQ-12), the Beck Depression Inventory (BDI), Spielberger's State Anxiety Inventory State form (STAI-S), the Fatigue Scale-14 (FS-14), and the Profile of Mood States (POMS) before consultation. They were also asked to rate anxiety levels before and after consultation using a visual analogue scale (VAS). RESULTS: In total, 1390 women completed the study. The mean ± standard deviation of GHQ-12 (bi-modal) and GHQ-12 (Likert) scores were 4.04 ± 3.17 and 15.19 ± 5.30, respectively. Among these women, 48.4% had a GHQ-12 (bi-modal) score ≥4 and 76.7% had a GHQ-12 (Likert) score >12, indicating distress. The mean ± standard deviation of BDI, STAI-S, and FS-14 scores were 9.35 ± 7.19, 53.81 ± 10.95, and 2.40 ± 0.51, respectively. The VAS score significantly decreased after consultation (P<0.001). Compared with women without a history of miscarriage, women with a previous miscarriage had higher GHQ-12, BDI, and POMS scores (except for fatigue-inertia and vigour-activity subscales). A higher bleeding score was strongly positively correlated with GHQ-12 (Likert) score. There were weak correlations between pain score and the GHQ-12 (bi-modal) ≥4, BDI >12, and POMS scores (except for confusion-bewilderment subscale which showed a strong positive correlation). CONCLUSION: Women with threatened miscarriage experience a considerable psychological burden, emphasising the importance of early recognition for timely management.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Thermo-mechanical processing of brass components for potable-water usage increases risks of Pb leaching.

The problem of lead contamination in potable water has been a serious concern in different countries. Although the use of leaded welding solder has been banned and brass components used in potable water pipework have to be of the nominally "lead-free" grade in most jurisdictions, incidents of excessive lead leaching are still reported. The widely advocated explanation of lead leaching from brass components in terms of corrosion and the formation of electrochemical cells is inadequate since mechanical cutting is also known to cause lead segregation on brass surfaces. In this study, the effects of lead segregation on brass surfaces and subsequent leaching to contacting water resulting from thermo-mechanical processing of the brass are studied. The results indicate that mechanical milling and polishing that replicate the common processing involved in pipeline installation yield a significant increase in surface lead, and a strong correlation exists between lead leaching and the plastic deformation of the brass surface. Furthermore, flame-torch treatment that replicates the common brazing of brass also results in a significant increase in surface lead. These results indicate that the common thermo-mechanical processing of brass piping components poses a real risk of lead contamination in potable water, and revision in the common protocols for handling lead components may be necessary.

External validation of a simple scoring system to predict pregnancy viability in women presenting to an early pregnancy assessment clinic.

INTRODUCTION: A scoring system combining clinical history and simple ultrasound parameters was developed to predict early pregnancy viability beyond the first trimester. The scoring system has not yet been externally validated. This study aimed to externally validate this scoring system to predict ongoing pregnancy viability beyond the first trimester. METHODS: This prospective observational cohort study enrolled women with singleton intrauterine pregnancies before 12 weeks of gestation. Women underwent examination and ultrasound scan to assess gestational sac size, yolk sac size, and fetal pulsation status. A pregnancy-specific viability score was derived in accordance with the Bottomley score. Pregnancy outcomes at 13 to 16 weeks were documented. Receiver-operating characteristic curve analysis was used to assess the discriminatory performance of the scoring system. RESULTS: In total, 1508 women were enrolled; 1271 were eligible for analysis. After adjustment for covariates, miscarriage (13%) was significantly associated with age ≥35 years (odds ratio [OR]=1.99, 95% confidence interval [CI]: 1.19-3.34), higher bleeding score (OR=2.34, 95% CI: 1.25-4.38), gestational age (OR=1.17, 95% CI: 1.13-1.22), absence of yolk sac (OR=4.73, 95% CI: 2.11-10.62), absence of fetal heart pulsation (OR=3.57, 95% CI: 1.87-6.84), mean yolk sac size (OR=1.25, 95% CI: 1.06-1.47), and fetal size (OR=0.82, 95% CI: 0.77-0.88). The area under the receiver operating characteristic curve was 0.91 (95% CI: 0.89-0.93). Viability score of ≥1 corresponded to a >90% probability of viable pregnancy. CONCLUSIONS: The scoring system was easy to use. A score of ≥1 could be used to counsel women who have a high likelihood of viable pregnancy beyond the first trimester.

Adaptation of tape removal test for measurement of sensitivity in perineal area of rat.

Regeneration after spinal cord injury is a goal of many studies. Although the most obvious target is to recover motor function, restoration of sensation can also improve the quality of life after spinal cord injury. For many patients, recovery of sensation in the perineal and genital area is a high priority. Currently there is no experimental test in rodents for measuring changes in sensation in the perineal and genital area after spinal cord injury. The aim of our study was to develop a behavioural test for measuring the sensitivity of the perineal and genital area in rats. We have modified the tape removal test used routinely to test sensorimotor deficits after stroke and spinal cord injury to test the perineal area with several variations. A small piece of tape (approximately 1 cm2) was attached to the perineal area. Time to first contact and to the removal of the tape was measured. Each rat was trained for 5 consecutive days and then tested weekly. We compared different rat strains (Wistar, Sprague-Dawley, Long-Evans and Lewis), both genders, shaving and non-shaving and different types of tape. We found that the test was suitable for all tested strains, however, Lewis rats achieved the lowest contact times, but this difference was significant only for the first few days of learning the task. There were no significant differences between gender and different types of tape or shaving. After training the animals underwent dorsal column lesion at T10 and were tested at day 3, 8, 14 and 21. The test detected a sensory deficit, the average time across all animals to sense the stimulus increased from 1'32 up to 3'20. There was a strong relationship between lesion size and tape detection time, and only lesions that extended laterally to the dorsal root entry zone produced significant sensory deficits. Other standard behavioural tests (BBB, von Frey, ladder and Plantar test) were performed in the same animals. There was a correlation between lesion size and deficit for the ladder and BBB tests, but not for the von Frey and Plantar tests. We conclude that the tape removal test is suitable for testing perineal sensation in rats, can be used in different strains and is appropriate for monitoring changes in sensation after spinal cord injury.

Uterine Fibroid Symptom and Health-related Quality of Life Questionnaire: a Chinese translation and validation study.

INTRODUCTION: The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is a validated tool in English language to assess treatment outcomes for women with fibroids. We performed a Chinese (traditional) translation and cultural adaptation of it and evaluated its reliability, validity, and responsiveness. METHODS: Overall, 223 Chinese women aged ≥18 years with uterine fibroids self-administered the UFS-QOL, Short-Form Health Survey-12, pictorial blood loss assessment chart (PBAC), and a visual analogue scale (VAS) on fibroid-related symptom severity. Demographics and haemoglobin levels were recorded; physical examination and ultrasound for size of fibroids were performed. Half of the women were followed up 6 months later for responsiveness. RESULTS: Cronbach's alpha coefficients ranged from 0.706 to 0.937, demonstrating high internal reliability. The intra-class correlation coefficients to measure test-retest reliability implied excellent stability of symptom scores (0.819, P<0.001), health-related quality of life scores (0.897, P<0.001), and all subscales (range 0.721-0.870, P<0.001). Convergent validity was demonstrated by positive correlations between the findings of various symptom severity assessment tools (PBAC, VAS on fibroid-related symptoms severity) and the symptom severity domain of Chinese UFS-QOL. In addition, there were positive correlations between health-related quality of life scores of Chinese UFS-QOL and the corresponding subscales of the Short-Form Health Survey-12. Responsiveness was shown by reduction of symptom severity scores and improvement of health-related quality of life scores after treatment. CONCLUSIONS: The Chinese version of the UFS-QOL is valid, reliable, and responsive to changes after treatment.

The Use of Post-ablation Stimulated Thyroglobulin in Predicting Clinical Outcomes in Differentiated Thyroid Carcinoma - What Cut-off Values Should We Use?

AIMS: Recently published international guidelines recommended using the stimulated thyroglobulin (sTg) post-radioactive iodine (RAI) ablation, in conjunction with tumour stage, as a risk stratification factor. The choice of cut-off values for sTg, namely 1 and 10 ng/ml, was, however, largely based on the functional sensitivities of the assays used, with relatively few published data addressing the prognostic impact of alternative cut-off values. Our study aims to provide data on the prognostic value of sTg at different levels of sensitivities and specificities. MATERIALS AND METHODS: We conducted a retrospective review of all adult cases of differentiated thyroid carcinoma receiving RAI ablation at our centre from 2008 to 2010. All patients had sTg measured at around 6 months post-ablation. The functional sensitivity of our assay was 0.5 ng/ml. The outcome was adverse clinical event, defined as cancer-related death, persistent macroscopic disease demonstrable on imaging (including radioisotope scan) and/or receiving further treatment for persistent or recurrent disease. A receiver operating characteristic (ROC) analysis was carried out. RESULTS: We identified 140 patients treated in the review period, with 106 of them suitable for further analysis. The reasons for exclusion included the presence of anti-thyroglobulin antibodies and medullary or anaplastic histological subtypes. Most (54.7%) had intermediate-risk disease as per the American Thyroid Association classification (2009). The median follow-up duration was 6.4 years; the minimum, excluding deaths, was 5.0 years. ROC analysis showed that the optimal cut-off value of sTg for predicting adverse clinical events was >1.0 ng/ml, associated with a sensitivity of 90.9%, a specificity of 81.0%, a positive predictive value of 55.6% and a negative predictive value of 97.1%. CONCLUSION: Based on ROC analysis of sensitivities and specificities, our data showed that a post-ablation sTg value of 1 ng/ml is the optimal cut-off in prognostication of adverse clinical events.

MRONJ risk of adjuvant bisphosphonates in early stage breast cancer.

Medication-related osteonecrosis of the jaw (MRONJ) has most commonly been associated with bisphosphonates. The routine uses of these drugs are now well established predominantly in metastatic cancer with bone involvement, multiple myeloma, hypercalcaemia, osteoporosis and Paget's disease. Recently, however, the use of bisphosphonates in early breast cancer has shown a reduction in breast cancer recurrence and breast cancer deaths. This new indication for their use approximates to a further 20,000 women per year in the UK being prescribed bisphosphonates. In this article, we consider the dental impact of this new use of bisphosphonates, report on the rates of MRONJ seen in early breast cancer bisphosphonate trials and discuss strategies aimed at minimising the risk of bisphosphonate-exposed patients developing MRONJ.

A study of human neutrophil antigen genotype frequencies in Hong Kong.

BACKGROUND: Alloantibodies against human neutrophil antigens (HNA) are associated with a variety of clinical conditions. Over the past decade, the allelic and genotypic frequencies of the five HNA systems have been evaluated. Although the HNA system is less polymorphic than human leukocyte antigens (HLA), significant differences in the genotypic and allele frequencies still exist in different populations, even those living in close proximity. OBJECTIVES: To delineate HNA genotypic and allele frequencies to provide vital information on estimating the risk of HNA-associated diseases for our local population. METHODS: Using a validated, in-house-developed assay, genotyping for HNA-1, HNA-3, HLA-4 and HNA-5 was performed on 300 samples from Chinese blood donors from Hong Kong. In addition, the frequency of the HNA-2 c.843A > T allele was also determined. RESULTS: The allele frequencies of HNA-1a, -1b and -1c alleles were 67·8, 31·5 and 0%, respectively, whereas the frequencies of HNA-3a and HNA-3b were 71·0 and 29·0%, respectively. The frequencies of HNA-4a and -4b alleles were 99·5 and 0·5%, respectively, and for HNA-5a and -5b, alleles were 85·2 and 14·8%, respectively. Homozygotes for the HNA-2 c.843 TT variant were absent in our population, whereas only <4% of the population were c.843AT heterozygote carriers. CONCLUSIONS: This is the first study to define HNA genotype and allele frequencies using a validated modified in-house PCR-SSP method in the Hong Kong Chinese blood donor population. Our approach provides a cost-effective assay for conducting routine HNA typing and facilitates the incorporation of these assays into routine clinical service. Our results are comparable with those reported in the Guangzhou Chinese population, but the allele frequencies in our Hong Kong Chinese population are significantly different from the reported European frequencies, confirming that a geographical difference exists for HNA allele frequencies.