Body composition and components of energy expenditure in children with end-stage liver disease

Background: Better understanding of body composition and energy metabolism in pediatric liver disease may provide a scientific basis for improved medical therapy aimed at achieving optimal nutrition, slowing progression to end-stage liver disease (ESLD), and improving the outcome of liver transplantation. Methods: Twenty-one children less than 2 years of age with ESLD awaiting liver transplantation and 15 healthy, aged-matched controls had body compartment analysis using a four compartment model (body cell mass, fat mass, extracellular water, and extracellular solids). Subjects also had measurements of resting energy expenditure (REE) and respiratory quotient (RQ) by indirect calorimetry. Nine patients and 15 control subjects also had measurements of total energy expenditure (TEE) using doubly labelled water. Results: Mean weights and heights were similar in the two groups. Compared with control subjects, children with ESLD had higher relative mean body cell mass (33 ± 2% vs 29 ± 1% of body weight, P < 0.05), but had similar fat mass, extracellular water, and extracellular solid compartments (18% vs 20%, 41% vs 38%, and 7% vs 13% of body weight respectively). Compared with control subjects, children with ESLD had 27% higher mean REE/body weight (0.285 ± 0.013 vs 0.218. ± 0.013 mJ/kg/24h, P < 0.001), 16% higher REE/unit cell mass (P < 0.05); and lower mean RQ (P < 0.05). Mean TEE of patients was 4.70 ± 0.49 mJ/24h vs 3.19 ± 0.76 in controls, (P < 0.01). Conclusions: In children, ESLD is a hypermetabolic state adversely affecting the relationship between metabolic and non-metabolic body compartments. There is increased metabolic activity within the body cell mass with excess lipid oxidation during fasting and at rest. These findings have implications for the design of appropriate nutritional therapy.

Successful topical tacrolimus (FK506) therapy in a child with pyoderma gangrenosum

The inflammatory skin disease pyoderma gangrenosum is characterized by destructive ulceration, typically occurring on the calves and thighs and less commonly on the buttocks and face. Lesions vary in size and may be multiple, often rapidly ulcerating to form deep painful wounds. Ulcers characteristically have ragged purple edges that overhang. In many patients a concomitant condition can be identified such as inflammatory bowel disease, rheumatoid arthritis, chronic autoimmune hepatitis, and various hematologic and solid tumours (1,2). Treatment of these ulcers in the past has been disappointing. The large lesions usually run a chronic course and heal very slowly, with traditional dressings often in combination with systemic steroids or immunosuppressants. Since 1998, a small number of case have been reported of adults with pyoderma gangrenosum whose lesions heal with the use of topical tacrolimus (FK506) (2–4). We report, to the best of our knowledge, the first successful treatment of a child with pyoderma gangrenosum using topical tacrolimus.

Investigating the potential of Shikonin, a Chinese herbal medicine, as a novel scar remediation therapy

This project investigates for the first time the biological mechanisms underlying the anecdotal use of Shikonin, an active component extracted from the Chinese herbal medicine "Zi Cao", as a treatment for hypertrophic scars. Compelling molecular and cellular evidence was generated supporting the therapeutic value of Shikonin as a scar treatment, suggesting that further development of this agent is warranted.

Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease

Background: Inflammation and biomechanical factors have been associated with the development of vulnerable atherosclerotic plaques. Lipid-lowering therapy has been shown to be effective in stabilizing them by reducing plaque inflammation. Its effect on arterial wall strain, however, remains unknown. The aim of the present study was to investigate the role of high- and low-dose lipid-lowering therapy using an HMG-CoA reductase inhibitor, atorvastatin, on arterial wall strain. Methods and Results: Forty patients with carotid stenosis >40% were successfully followed up during the Atorvastatin Therapy: Effects on Reduction Of Macrophage Activity (ATHEROMA; ISRCTN64894118) Trial. All patients had plaque inflammation as shown by intraplaque accumulation of ultrasmall super paramagnetic particles of iron oxide on magnetic resonance imaging at baseline. Structural analysis was performed and change of strain was compared between high- and low-dose statin at 0 and 12 weeks. There was no significant difference in strain between the 2 groups at baseline (P=0.6). At 12 weeks, the maximum strain was significantly lower in the 80-mg group than in the 10-mg group (0.085±0.033 vs. 0.169±0.084; P=0.001). A significant reduction (26%) of maximum strain was observed in the 80-mg group at 12 weeks (0.018±0.02; P=0.01). Conclusions: Aggressive lipid-lowering therapy is associated with a significant reduction in arterial wall strain. The reduction in biomechanical strain may be associated with reductions in plaque inflammatory burden.

The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease

Objectives: The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. Background: Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. Methods: Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (ΔSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. Results: Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (ΔSI 0.13; p = 0.0003) and at 12 weeks (ΔSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. Conclusions: Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).

Acceptance of prostitution and its social determinants in Canada

The nature of collective perception of prostitution is understudied in Canada. Except some rudimentary reports on the percentages of the key legal options, multivariate analysis has never been used to analyze the details of public opinion on prostitution. The current study explores the trend of public attitude toward prostitution acceptability in Canada over a 25-year span and examines the social determinants of the acceptability of prostitution, using structural equation modeling (SEM), which allows researchers to elaborate both direct and indirect effects (through mediating variables) on the outcome variable. Results show that the public has become more acceptant of prostitution over time. In addition, the less religious, less authoritarian, and more educated are more acceptant of prostitution than the more religious, more authoritarian, and less well educated. The effects of religiosity and authoritarianism mediate out the direct effects of age, gender, gender equality, marriage, marriage as an outdated institution, Quebec, race, and tolerance. The findings may serve as a reference point for the law reform regarding the regulation of prostitution in Canada.

A dosimetric retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC)

Purpose A retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC). Methods and materials Five randomly selected early stage lung cancer patients were included in the study. For each patient, four plans were created: the SBRT plan and three VMAT plans using different optimisation methodologies. A total of 20 different plans were evaluated. The dose parameters of dose conformity results and the target dose constraints results were compared for these plans. Results The mean planning target volume (PTV) for all the plans (SBRT and VMAT) was 18·3 cm3, with a range from 15·6 to 20·1 cm3. The maximum dose tolerance to 1 cc of all the plans was within 140% (84 Gy) of the prescribed dose, and 95% of the PTV of all the plans received 100% of the prescribed dose (60 Gy). In all the plans, 99% of the PTV received a dose >90% of the prescribed dose, and the mean dose in all the plans ranged from 67 to 72 Gy. The planning target dose conformity for the SBRT and the VMAT (0°, 15° collimator single arc plans and dual arc) plans showed the tightness of the prescription isodose conformity to the target. Conclusions SBRT and VMAT are radiotherapy approaches that increase doses to small tumour targets without increasing doses to the organs at risk. Although VMAT offers an alternative to SBRT for NSCLC and the potential advantage of VMAT is the reduced treatment times over SBRT, the statistical results show that there was no significant difference between the SBRT and VMAT optimised plans in terms of dose conformity and organ-at-risk sparing.

Emotional intelligence development in radiation therapy students: A longitudinal study

Purpose: Emotional intelligence (EI) is an increasingly important aspect of a health professional’s skill set. It is strongly associated with empathy, reflection and resilience; all key aspects of radiotherapy practice. Previous work in other disciplines has formed contradictory conclusions concerning development of EI over time. This study aimed to determine the extent to which EI can develop during a radiotherapy undergraduate course and identify factors affecting this. Methods and materials: This study used anonymous coded Likert-style surveys to gather longitudinal data from radiotherapy students relating to a range of self-perceived EI traits during their 3-year degree. Data were gathered at various points throughout the course from the whole cohort. Results: A total of 26 students provided data with 14 completing the full series of datasets. There was a 17·2% increase in self-reported EI score with a p-value<0·0001. Social awareness and relationship skills exhibited the greatest increase in scores compared with self-awareness. Variance of scores decreased over time; there was a reduced change in EI for mature students who tended to have higher initial scores. EI increase was most evident immediately after clinical placements. Conclusions: Radiotherapy students increase their EI scores during a 3-year course. Students reported higher levels of EI immediately after their clinical placement; radiotherapy curricula should seek to maximise on these learning opportunities.

Quality of life changes during conformal radiation therapy for prostate carcinoma

BACKGROUND: The objective of this study was to describe prospectively quality of life (QOL) before and after radiotherapy for patients with prostate carcinoma. METHODS: Forty-three patients with T1-T3 prostate carcinoma who underwent conformal external beam radiation therapy were randomized either to the complete European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (EORTC QLQ-C30) or the Medical Outcomes Study Group Short Form Health Survey (SF-36) at baseline, at 3 weeks and 6 weeks after initial treatment, and at 6 weeks and 5 months after the completion of radiotherapy. The measures were self-reported patient QOL, and values are given as the mean +/- standard error of the mean. Changes in QOL are described from baseline to the end of treatment in both questionnaire groups. RESULTS: Emotional role functioning, as measured with the SF-36 questionnaire, significantly improved from 68.2 +/- 9.9 at baseline to 93.3 +/- 5.2 at the end of therapy (P = 0.02). The EORTC QLQ-C30 questionnaire revealed consistent values of emotional functioning during treatment (72.7 +/- 5.9 at baseline) but showed a significant improvement 6 weeks after therapy (89.0 +/- 4.4; P = 0.01). Role functioning deteriorated from 80.1 +/- 6.5 at baseline to 62.5 +/- 8.8 at the end of radiotherapy (P = 0.02). Symptoms of fatigue were shown to increase significantly from 26.9 +/- 6.0 at baseline to 37.7 +/- 7.6 at the end of therapy (P = 0.02). No significant changes in the other dimensions were observed in either questionnaire. CONCLUSIONS: After radiotherapy for prostate carcinoma, patients experience a temporary deterioration of fatigue and role functioning, as measured with the EORTC QLQ-C-30. Despite physical deterioration, the authors observed an improvement in emotional functioning scores with both questionnaires. This may have been due to psychological adaptation and coping.

Implementing music therapy on an adolescent inpatient unit: A mixed-methods evaluation of acceptability, experience of participation and perceived impact

Objective: We aimed to assess the feasibility of delivering a music therapy program on adolescent psychiatric wards. Method: We undertook a mixed-methods evaluation of a pilot program. Various active and receptive techniques were employed in group music therapy sessions delivered as part of a structured clinical program. Data collected in interviews with participants and staff and feedback questionnaires were thematically and descriptively analysed and triangulated. Results: Data from 62 questionnaires returned by 43 patients who took part in 16 music therapy sessions, and seven staff, evidenced strong support for music therapy. Patients typically reported experiencing sessions as relaxing, comforting, uplifting, and empowering; >90% would participate by choice and use music therapeutically in the future. Staff endorsed music therapy as valuable therapeutically, reporting that patients engaged enthusiastically and identified sessions as improving their own moods and ward milieu. Conclusions: Integration of music therapy in inpatient treatment of adolescents is feasible and acceptable, and is valued by staff and patients as a complement to ‘talking therapies’. Participation is enjoyed and associated with outcomes including improvement in mood, expression of feelings and social engagement consistent with recovery.

Nutritional intake of opioid replacement therapy patients in community pharmacies: A pilot study

Aim: Opioid replacement therapy (ORT) is an established therapy for a patient group that has been associated with nutrition-related comorbidities. This paper aims to assess the nutritional intake and supplementation in ORT patients, determine the extent of nutritional/dietary advice supplied to ORT patients and to briefly examine patients' perception of pharmacists' provision of nutritional advice. Methods: The nutritional intake of ORT patients receiving treatment in community pharmacies within the Australian Capital Territory was assessed via a 24-hour recall survey. Food intake data were analysed via nutrient analysis software and compared with Australian Nutrition Reference Values and the nutrient intakes of the Australian population. Patients were surveyed to determine supplement use and perceptions of nutritional advice gained by pharmacists. Results: Potential insufficient intake of various macronutrients and micronutrients was observed in both sexes. Less than 25 of patients recorded supplement use. Fifteen percent of males and 21 of females stated that they had approached a pharmacist with a nutrition-related query. All patients who received nutritional advice followed the advice. Conclusions: ORT patients dosing at community pharmacies appear to have poor nutritional intake. ORT patients appear to be receptive to pharmacist's advice. Community pharmacists can potentially increase the beneficial health outcomes in this population through the proactive supply of accurate nutritional advice.

Using genomic data to make indirect (and unauthorized) estimates of disease risk

The number of genetic factors associated with common human traits and disease is increasing rapidly, and the general public is utilizing affordable, direct-to-consumer genetic tests. The results of these tests are often in the public domain. A combination of factors has increased the potential for the indirect estimation of an individual's risk for a particular trait. Here we explain the basic principals underlying risk estimation which allowed us to test the ability to make an indirect risk estimation from genetic data by imputing Dr. James Watson's redacted apolipoprotein E gene (APOE) information. The principles underlying risk prediction from genetic data have been well known and applied for many decades, however, the recent increase in genomic knowledge, and advances in mathematical and statistical techniques and computational power, make it relatively easy to make an accurate but indirect estimation of risk. There is a current hazard for indirect risk estimation that is relevant not only to the subject but also to individuals related to the subject; this risk will likely increase as more detailed genomic data and better computational tools become available.

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

Reliability and validity of objective measures of physical activity in youth with cerebral palsy who are ambulatory

BACKGROUND Physical therapy for youth with cerebral palsy (CP) who are ambulatory includes interventions to increase functional mobility and participation in physical activity (PA). Thus, reliable and valid measures are needed to document PA in youth with CP. OBJECTIVE The purpose of this study was to evaluate the inter-instrument reliability and concurrent validity of 3 accelerometer-based motion sensors with indirect calorimetry as the criterion for measuring PA intensity in youth with CP. METHODS Fifty-seven youth with CP (mean age=12.5 years, SD=3.3; 51% female; 49.1% with spastic hemiplegia) participated. Inclusion criteria were: aged 6 to 20 years, ambulatory, Gross Motor Function Classification System (GMFCS) levels I through III, able to follow directions, and able to complete the full PA protocol. Protocol activities included standardized activity trials with increasing PA intensity (resting, writing, household chores, active video games, and walking at 3 self-selected speeds), as measured by weight-relative oxygen uptake (in mL/kg/min). During each trial, participants wore bilateral accelerometers on the upper arms, waist/hip, and ankle and a portable indirect calorimeter. Intraclass coefficient correlations (ICCs) were calculated to evaluate inter-instrument reliability (left-to-right accelerometer placement). Spearman correlations were used to examine concurrent validity between accelerometer output (activity and step counts) and indirect calorimetry. Friedman analyses of variance with post hoc pair-wise analyses were conducted to examine the validity of accelerometers to discriminate PA intensity across activity trials. RESULTS All accelerometers exhibited excellent inter-instrument reliability (ICC=.94-.99) and good concurrent validity (rho=.70-.85). All accelerometers discriminated PA intensity across most activity trials. LIMITATIONS This PA protocol consisted of controlled activity trials. CONCLUSIONS Accelerometers provide valid and reliable measures of PA intensity among youth with CP.

Public good provision and the welfare effects of indirect tax harmonisation

The paper considers the welfare effect of the harmonisation of indirect taxes in two open economies. The revenue from taxation is used for the production of a non-tradeable public good. The welfare levels are affected via two channels: (i) changes in the levels of public good provision, and (ii) changes in deadweight loss associated with the taxes. We develop a number of rules of harmonisation and derive conditions under which they lead to potential Pareto improvement.