Quality of life and survival in patients treated with radical chemoradiation alone for oesophageal cancer

Aims: To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. Materials and methods: Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. Results: The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. Conclusions: Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials. © 2007 The Royal College of Radiologists.

Developing Performance Mentoring Handbook

Over the last 40 years, the term mentoring has been hailed as an important workplace learning activity, and applied in a variety on contexts such as government departments, hospitals, schools and community settings. It has been used to support the learning and development of new employees and leaders, as well as for the purposes of talent management and retention. Not surprisingly, its meaning often depends on the purpose for which it has been used and the particular context in which it has been applied. Most adults can identify a person who has had a major positive impact on their lives, e.g. a boss, a coach or a teacher, who has acted as a mentor to them. Today, organisations are embracing the concept of mentoring as a professional development too through which improvements in efficiency, productivity and the passing of corporate knowledge and leadership skills can occur.

Pupil shape as viewed along the horizontal visual field

Purpose: Changes in pupil size and shape are relevant for peripheral imagery by affecting aberrations and how much light enters and/or exits the eye. The purpose of this study is to model the pattern of pupil shape across the complete horizontal visual field and to show how the pattern is influenced by refractive error. Methods: Right eyes of thirty participants were dilated with 1% cyclopentolate and images were captured using a modified COAS-HD aberrometer alignment camera along the horizontal visual field to ±90°. A two lens relay system enabled fixation at targets mounted on the wall 3m from the eye. Participants placed their heads on a rotatable chin rest and eye rotations were kept to less than 30°. Best-fit elliptical dimensions of pupils were determined. Ratios of minimum to maximum axis diameters were plotted against visual field angle. Results: Participants’ data were well fitted by cosine functions, with maxima at (–)1° to (–)9° in the temporal visual field and widths 9% to 15% greater than predicted by the cosine of the field angle . Mean functions were 0.99cos[( + 5.3)/1.121], R2 0.99 for the whole group and 0.99cos[( + 6.2)/1.126], R2 0.99 for the 13 emmetropes. The function peak became less temporal, and the width became smaller, with increase in myopia. Conclusion: Off-axis pupil shape changes are well described by a cosine function which is both decentered by a few degrees and flatter by about 12% than the cosine of the viewing angle, with minor influences of refraction.

Ocular surface health with contact lens wear

Eye care practitioners (ECPs) would tend to agree that wearing contact lenses increases the risk for infection, but millions of patients are still fitted with lenses every year because ECPs feel that the risk is manageable and that their patients' eye health can be protected. The Fusarium and Acanthamoeba keratitis outbreaks of years past were a wake-up call to manufacturers, ECPs, and regulatory agencies that risk cannot be managed without diligence, and that the complex relationship between contact lens materials, contact lens solutions, and compliance needs to be better understood in order to optimize the efficacy of contact lens care and improve care guidelines.

Why are there Different Age Related Trends for Different Chemicals?

Persistent organic pollutants (POPs) such as dioxins, PCBs, persistent organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) as well as perfluorinated compounds (PFCs) and triclosan are ubiquitous in the human population. In Australia, we have pooled and subsequently analysed over 10 000 human serum samples for the determination of these chemicals by age group (0–0.5; 0.6–1; 1.1–1.5; 1.6–2; 2.1–2.5; 2.6–3; 3.1–3.5; 3.6–4; 4.1–6; 6.1–9; 9.1–12; 12.1–15; 16–30; 31–45; 46–60 and >60 years) and gender. The results of this analysis were then used to assess the trends of these different chemicals as a function of age, gender and to a lesser extent region. Our data demonstrate clear chemical specific age trends. In particular we demonstrate that for the traditional POPs there is an increase in body burden with age whereas the opposite is true for chemicals such as PBDEs. For PFCs we find chemical specific age trends that vary from compound to compound. For triclosan we show that no apparent age trend is observable. The results of the study and its implications to the collection and archiving of samples for retrospective analysis are discussed.

Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone

Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Δ4-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Δ4-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Δ4-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Δ4-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.

Obesity and comorbid risk factors for cardiovascular disease among physically inactive patients with musculoskeletal disorders : a targeted intervention for this priority patient group is warranted

Introduction The benefits of physical activity are established and numerous; not the least of which is reduced risk of negative cardiovascular events. While sedentary lifestyles are having negative impacts across populations, people with musculoskeletal disorders may face additional challenges to becoming physically active. Unfortunately, interventions in ambulatory hospital clinics for people with musculoskeletal disorders primarily focus on their presenting musculoskeletal complaint with cursory attention given to lifestyle risk factors; including physical inactivity. This missed opportunity is likely to have both personal costs for patients and economic costs for downstream healthcare funders. Objectives The objective of this study was to investigate the presence of obesity, diabetes, diagnosed cardiac conditions, and previous stroke (CVA) among insufficiently physically active patients accessing (non-surgical) ambulatory hospital clinics for musculoskeletal disorders to indicate whether a targeted risk-reducing intervention is warranted. Methods A sub-group analysis of patients (n=110) who self-reported undertaking insufficient physical activity level to meet national (Australian) minimum recommended guidelines was conducted. Responses to the Active Australia Survey were used to identify insufficiently active patients from a larger cohort study being undertaken across three (non-surgical) ambulatory hospital clinics for musculoskeletal disorders. Outcomes of interest included body mass index, Type-II diabetes, diagnosed cardiac conditions, previous CVA and patients’ current health-related quality of life (Euroqol-5D). Results The mean (standard deviation) age of inactive patients was 56 (14) years. Body mass index values indicated that n=80 (73%) were overweight n=26 (24%), or obese n=45 (49%). In addition to their presenting condition, a substantial number of patients reported comorbid diabetes n=23 (21%), hypertension n=25 (23%) or an existing heart condition n=14 (13%); 4 (3%) had previously experienced a CVA as well as other comorbid conditions. Health-related quality of life was also substantially impacted, with a mean (standard deviation) multi-attribute utility score of 0.51 (0.32). Conclusion A range of health conditions and risk factors for further negative health events, including cardiovascular complications, consistent with physically inactive lifestyles were evident. A targeted risk-reducing intervention is warranted for this high risk clinical group.

Machine learning for activity recognition : hip versus wrist data

Problem addressed Wrist-worn accelerometers are associated with greater compliance. However, validated algorithms for predicting activity type from wrist-worn accelerometer data are lacking. This study compared the activity recognition rates of an activity classifier trained on acceleration signal collected on the wrist and hip. Methodology 52 children and adolescents (mean age 13.7 +/- 3.1 year) completed 12 activity trials that were categorized into 7 activity classes: lying down, sitting, standing, walking, running, basketball, and dancing. During each trial, participants wore an ActiGraph GT3X+ tri-axial accelerometer on the right hip and the non-dominant wrist. Features were extracted from 10-s windows and inputted into a regularized logistic regression model using R (Glmnet + L1). Results Classification accuracy for the hip and wrist was 91.0% +/- 3.1% and 88.4% +/- 3.0%, respectively. The hip model exhibited excellent classification accuracy for sitting (91.3%), standing (95.8%), walking (95.8%), and running (96.8%); acceptable classification accuracy for lying down (88.3%) and basketball (81.9%); and modest accuracy for dance (64.1%). The wrist model exhibited excellent classification accuracy for sitting (93.0%), standing (91.7%), and walking (95.8%); acceptable classification accuracy for basketball (86.0%); and modest accuracy for running (78.8%), lying down (74.6%) and dance (69.4%). Potential Impact Both the hip and wrist algorithms achieved acceptable classification accuracy, allowing researchers to use either placement for activity recognition.

Health consequences of exposure to e-waste : a systematic review

Background The population exposed to potentially hazardous substances through inappropriate and unsafe management practices related to disposal and recycling of end-of-life electrical and electronic equipment, collectively known as e-waste, is increasing. We aimed to summarise the evidence for the association between such exposures and adverse health outcomes. Methods We systematically searched five electronic databases (PubMed, Embase, Web of Science, PsycNET, and CINAHL) for studies assessing the association between exposure to e-waste and outcomes related to mental health and neurodevelopment, physical health, education, and violence and criminal behaviour, from Jan 1, 1965, to Dec 17, 2012, and yielded 2274 records. Of the 165 full-text articles assessed for eligibility, we excluded a further 142, resulting in the inclusion of 23 published epidemiological studies that met the predetermined criteria. All studies were from southeast China. We assessed evidence of a causal association between exposure to e-waste and health outcomes within the Bradford Hill framework. Findings We recorded plausible outcomes associated with exposure to e-waste including change in thyroid function, changes in cellular expression and function, adverse neonatal outcomes, changes in temperament and behaviour, and decreased lung function. Boys aged 8–9 years living in an e-waste recycling town had a lower forced vital capacity than did those living in a control town. Significant negative correlations between blood chromium concentrations and forced vital capacity in children aged 11 and 13 years were also reported. Findings from most studies showed increases in spontaneous abortions, stillbirths, and premature births, and reduced birthweights and birth lengths associated with exposure to e-waste. People living in e-waste recycling towns or working in e-waste recycling had evidence of greater DNA damage than did those living in control towns. Studies of the effects of exposure to e-waste on thyroid function were not consistent. One study related exposure to e-waste and waste electrical and electronic equipment to educational outcomes. Interpretation Although data suggest that exposure to e-waste is harmful to health, more well designed epidemiological investigations in vulnerable populations, especially pregnant women and children, are needed to confirm these associations. Funding Children's Health and Environment Program, Queensland Children's Medical Research Institute, The University of Queensland, Australia.

Epidemiology and risk factors of oral cancer in South Africa

Head and neck cancers are some of the leading cancers in the coloured and black South African male population and the perception exists that the incidence rates are rising. Aims: To determine the standardised morbidity rates and some of the risk factors for oral cancer in South Africa. Methods: Using histologically verified data from the National Cancer Registry, the age standardised incidence rates (ASIR) and life-time risks (LR) of oral cancer in South Africa were calculated for 1988-1991.2. In an ongoing case control study (1995 +) among black patients in Johannesburg/Soweto, adjusted odds ratios for developing oral cancers in relation to tobacco and alcohol consumption were calculated. Results: Coloured males vs. females: ASIR 13.13 vs. 3.5 (/100,000/year), LR 1:65 vs. 1:244. Black males vs. females: ASIR 9.06 vs. 1.75, LR 1:86 and 1:455. White males vs. females: ASIR 8.06 vs. 3.18, LR 1:104 vs. 1:278. Asian males vs. females: ASIR 5.24 vs. 6.66, LR 1:161 vs. 1:125. The odds ratio for oral cancer in black males in relation to smoking was 7.0 (95% CI 3.0-14.6) and daily alcohol consumption 1.3 (95% CI 0.6-2.8). In black females the odds ratios in relation to smoking were 3.9 (95% CI 1.7 8.9) and daily alcohol consumption 1.7(95% CI 0.7-4.1). Conclusions: The risk factors for oral cancer in South Africa are multiple and gender discrepancies in ASIR and LR signal differences in exposure to carcinogens. It is unclear whether the incidence of oral cancers will rise in the future.

Development of an evidence-based symptom checklist for symptoms of recurrence in women with endometrial cancer

Objective Women treated for endometrial cancer currently commonly attend clinic-based follow-up examinations for up to five years. This is based on little evidence and alternative models need to be investigated. This study aimed to identify currently available symptom checklists, determine the comprehensiveness of identified checklists, and generate an updated list of symptoms potentially associated with a recurrence of endometrial cancer for future testing within a prospective study. Methods/materials We conducted a systematic review of the literature extracting; routine follow-up schedules; proportion of patients with symptomatic or asymptomatic recurrence; symptoms of recurrence; prevalence of these symptoms at recurrence. Results Overall, three previous checklists, and 12 retrospective studies were identified meeting the selection criteria. The average rate of recurrence across the studies was 13% (range 3%-19%). The proportion of patients identified with a symptomatic recurrence varied widely (overall average 67%;range 41% to 91%). The most commonly reported symptoms were vaginal bleeding (25%), pain [not further described] (16%) and abdominal pain and/or discomfort and swelling (15%) which combined, represented 56% of the total reported symptoms. The three previous checklists listed 14 and this review identified an additional 24 symptoms (e.g. vaginal discharge, leg pain, constipation, headache and self-detected mass) not previously identified. Conclusion The newly developed symptom checklist expands previous ones, by an additional 24 symptoms. It will be used in a prospective cohort study to assess whether it is sensitive and specific enough to identify recurrence compared to current standard follow-up examinations.

Surgical fusion of early onset severe scoliosis increases survival in the child with rett syndrome: A population based study

Introduction. Rett Syndrome is a rare genetic neurodevelopmental disorder usually affecting females. Scoliosis is a common comorbidity and spinal fusion may be recommended if severe. Little is known about long term outcomes. We examined the impact of spinal fusion on survival and risk of severe lower respiratory tract infection (LRTI) in Rett Syndrome. Methods Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry of Rett Syndrome cases established in 1993, and the Australian Institute of Health and Welfare National Death Index database. An extended Cox regression model was used to estimate the effect of spinal surgery on survival in females who developed severe scoliosis (Cobb angle > 45 degrees). Generalized estimating equation modelling was used to estimate the effect of spinal surgery on the odds of developing severe LRTI. Results Severe scoliosis was identified in 140 cases (60.3%) of whom slightly fewer than half (48.6%) developed scoliosis prior to eight years of age. Scoliosis surgery was performed in 98 (69.0%) of those at a median age of 13 years 3 months (IQR 11 years 5 months – 14 years 10 months). After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (HR 0.30, 95% CI 0.12, 0.74, P = 0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06, 0.52, P = 0.002). Spinal fusion was not associated with reduction in the occurrence of a severe LRTI overall (OR 0.60, 95%CI 0.27, 1.33, P=0.206) but was associated with a large reduction in odds of severe LRTI among those with early onset scoliosis (OR 0.32, 95%CI 0.11, 0.93, P=0.036). Conclusion With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

The sleep patterns of infants and young children with gastro-oesophageal reflux

Objective: Sleep disturbance in gastro-oesophageal reflux disease (GORD) in infants and young children has not been systematically studied nor has this manifestation been compared with population norms. Methods: Sleep patterns of 102 infants and children aged 1 to 36 months with and without GORD, defined by pH monitoring, were analysed using the same questionnaire as in recent studies of normal sleep behaviour in this age range. Main outcome measures included time taken to settle at night, the number of night time wakenings requiring parental intervention, day time sleep patterns and parents problems with their childs' sleep behaviour. Results: Compared with the population norms (n=3102), those with GORD (n=76) had greater prevalence of night time waking >3/night (50% vs 13% aged 3-12 months; 60% vs 10% aged 12-24 months, P<0.001), requirement of parental intervention (82% vs 55% aged 3-12 months, P < 0.05; 92% vs 55% aged 12-24 months, P < 0.001), significantly delayed onset of sleeping through the night, and greater prevalence of daytime sleep beyond 24 months. Similar but less striking differences were seen comparing those with (n = 76) and without GORD (n = 26). Conclusions: Sleep interruption occurs more frequently in infants and children with GORD than population norms. Objective evaluation of infants and children with sleep disturbance after the age of 3 months may avoid unnecessary over or under diagnosis of GORD. Systematic investigation of the contribution of GORD to sleep disturbance in infants and young children is warranted

Distribution of ocular biometry in 7- and 14-year-old Chinese children

Purpose: To describe distributions of ocular biometry and their associations with refraction in 7- and 14-year-old children in urban areas of Anyang, central China. Methods: A total of 2271 grade 1 students aged 7.1 ± 0.4 years and 1786 grade 8 students aged 13.7 ± 0.5 years were measured with ocular biometry and cycloplegic refraction. A parental myopia questionnaire was administered to parents. Results: Mean axial length, anterior chamber depth, lens thickness, central corneal thickness, corneal diameter, corneal radius of curvature, axial length/corneal radius of curvature ratio, and spherical equivalent refraction were 22.72 ± 0.76 mm, 2.89 ± 0.24 mm, 3.61 ± 0.19 mm, 540.5 ± 31 μm, 12.06 ± 0.44 mm, 7.80 ± 0.25 mm, 2.91 ± 0.08, and +0.95 ± 1.05 diopters (D), respectively, in 7-year-old children. They were 24.39 ± 1.13 mm, 3.42 ± 0.41 mm, 3.18 ± 0.24 mm, 548.9 ± 33 μm, 12.03 ± 0.43 mm, 7.80 ± 0.26 mm, 3.13 ± 0.14, and −2.06 ± 2.20 D, respectively, in 14-year-old children. Compared with 7-year-old children, the older group had significantly more myopia (−3.0 D), longer axial length (1.7 mm), deeper anterior chamber depth (0.3 mm), thinner lens thickness (−0.2 mm), thicker central corneal thickness (10 μm), and greater axial length/corneal radius of curvature ratio (0.22) (all p < 0.001), as well as smaller corneal diameter (−0.03 mm, p = 0.02) and similar corneal radius of curvature. Sex differences were similar in both age groups, with boys having longer axial length (0.5 mm), deeper anterior chamber depth (0.1 mm), shorter lens thickness (0.03 mm), greater central corneal thickness (5 μm), greater corneal diameter (0.15 mm), and greater corneal radius of curvature (0.14 mm) than girls (all p < 0.01). The most important variables related to spherical equivalent refraction were vitreous length, corneal radius of curvature, and lens thickness. Conclusions: The 14-year-old group had larger parameter dimensions than the 7-year-old group except for corneal radius of curvature (unchanged) and lens thickness and corneal diameter (both smaller). Boys had large parameter dimensions than girls except for lens thickness (smaller). Axial length, corneal radius of curvature, and lens thickness were the most important determinants of refraction.