Implementation of an image-guided radiation therapy program: Lessons learnt and future challenges

The aim of this paper is to detail the experience obtained in implementing an image-guided radiation therapy program at the Northern Sydney Cancer Centre. This required retrofitting a Varian Clinac 21EX with an on-board imager. The commissioning and quality assurance procedures, organisation of a multidisciplinary image guided radiation therapy group, and the development of clinical protocols for orthogonal kV and cone beam computed tomography implementation are described. Reassessment of the image-guided radiation therapy program has continued as new equipment and software versions were made available in the department.     

Optimal sequence of implied modalities in the adjuvant setting of breast cancer treatment: an update on issues to consider

The adjuvant setting of early breast cancer treatment is an evolving field where different modalities must be combined to improve outcomes; moreover, quality of life of breast cancer survivors emerges as a new important parameter to consider, thus implying a better understanding of toxicities of these modalities. We have conducted a review focusing on the latest literature of the past 3 years, trying to evaluate the existing data on the maximum acceptable delay of radiotherapy when given as sole adjuvant treatment after surgery and the optimal sequence of all these modalities with respect to each other. It becomes evident radiotherapy should be given as soon as possible and within a time frame of 6-20 weeks. Chemotherapy is given before radiotherapy and hormone therapy. However, radiotherapy should be started within 7 months after surgery in these cases. Hormone therapy with tamoxifen might be given safely concomitantly or sequentially with radiotherapy although solid data are still lacking. The concurrent administration of letrozole and radiotherapy seems to be safe, whereas data on trastuzumab can imply only that it is safe to use concurrently with radiotherapy. Randomized comparisons of hormone therapy and trastuzumab administration with radiotherapy need to be performed.     

Permanent neonatal diabetes due to a novel insulin signal peptide mutation

We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51‐month‐old girl who presented with hyperglycemia in the neonatal period. Mutational analysis of KCNJ11 and INS was performed and this detected a novel heterozygous c.38T>G (p.Leu13Arg) INS de novo mutation. The non‐conservative change substitutes the highly conserved L¹³ residue within the hydrophobic core region of the preproinsulin signal peptide. Given the frequent tendency of heterozygous INS mutations to exhibit dominant negative disease pathogenesis, it is likely that the mutant preproinsulin perturbed the non‐mutant counterpart progression and processing within the β‐cells, and this resulted to a permanent form of congenital diabetes.     

GERICO-03 phase II trial of accelerated and partial breast irradiation in elderly women: Feasibility,reproducibility, and impact on functional status

PurposeTo analyze the feasibility, reproducibility, and impact on functional status of postoperative accelerated and partial breast irradiation (APBI) using interstitial high-dose rate-brachytherapy in women older than 70 years.Methods and MaterialsFrom July 2004 to April 2008, 46 patients were screened for enrollment in a nationwide prospective Phase II trial. A total of 40 patients were eligible according to the inclusion criteria (aged >70 years, T1–2 <30 mm, and pN0). The total delivered dose was 34 Gy of 10 fractions for 5 days. Feasibility and reproducibility were evaluated using a Quality Index (QI) defined as (V₁₀₀% ? clinical target volume)/V₁₀₀%. Skin toxicity was reported using Common Terminology Criteria for Adverse Events version 3.0. ABPI impact on functional dependence was evaluated using the Activity of Daily Living and Instrumental Activity of Daily Living scales. Reproducibility and feasibility were assessed with the optimal two-stage design of Simon.ResultsMedian age was 74 years (70–87 years). All patients were treated according to the protocol. Median Quality Index calculated for the 40 eligible patients was 13.3% (1–70%). It was considered acceptable, partially acceptable, and nonacceptable in 10, 28, and 2 patients, respectively. Within 12 months after APBI, overall rates of toxicity were 59%, 28%, and 2% for Grade 1, 2, and 3 events, respectively. Twelve months after APBI, 35 patients (87%) achieved excellent/good cosmetic result. Compared with baseline values, Activity of Daily Living and Instrumental Activity of Daily Living scores remained unchanged 6 and 12 months after APBI.ConclusionsAPBI by means of high-dose rate-brachytherapy is a feasible/reproducible technique without significant impact on functional dependence in the treatment of elderly women with early breast cancer.     

Facilitators and Barriers to Implementing Healthy School Canteen Intervention among Malaysian Adolescents: A Qualitative Study

This study evaluated implementing a school-based intervention to promote healthier dietary habits in the school environment among Malaysian adolescents using qualitative methods. This qualitative study was conducted in four secondary schools in Perak and Selangor (two urban and two rural schools) that received the intervention (either training or training and food subsidy). A total of eight focus groups (68 students aged 15 years old) and 16 in-depth interviews were conducted with canteen operators, school convenience shop operators, school teachers and school principals in each school. Thematic analysis was used to analyse the qualitative data to identify suitable themes. We found several initiatives and changes by the schools’ stakeholders to change to a healthy school canteen programme. The stakeholders also noticed the students’ food preferences that influence healthy food intake in canteens and convenience shops. The food vendors and school administrators also found that subsidising healthy meals might encourage healthy eating. Among barriers to implementing healthy school initiatives were the student’s perception of healthy food and their eating habits, which also affect the food vendors’ profit if they want to implement a healthy canteen. The school-based intervention has the potential to promotes healthier eating among school adolescents. Continuous training and monitoring of canteen operators and convenience shops are needed, including building partnerships and educating the students on healthy eating to cultivate healthy eating habits.     

Myeloid-derived suppressor cells in non-malignant and non-infectious liver disease

BackgroundMyeloid-derived suppressor cells (MDSC) have been described as potent immunosuppressive cells in malignant and infectious liver disease. However, little is known about their role in non-infectious or non-malignant disease. We sought to characterise MDSC in patients with chronic non-infectious or non-malignant liver disease.MethodsExplants obtained from 12 patients undergoing liver transplantation and blood from 30 patients treated for haemochromatosis at the Queen Elizabeth Hospital, Birmingham, were analysed for the frequency of functional CD14+ HLA-DR– monocytic MDSC. Functional capacity was defined as the capability to suppress proliferation of maximally stimulated, CFSE-labelled CD4 T cells using CD3/CD28-beads (Dynabeads, LifeTechnologies, UK) at a ratio of 1:1. Additionally, MDSC were analysed for their capacity to induce CD4 regulatory T cells (assessed by FoxP3 expression) in cells activated with CD2/CD3/CD28-beads (Miltenyi, Germany). Both MDSC and CD4 cells were isolated by magnet-activated cell-sorting using a combination of depletion steps and positive-selection-steps. Analysis of frequency and immunotyping of MDSC was performed with flow-cytometry.FindingsCD14+ HLA-DR– MDSC obtained both from liver tissue and peripheral blood were able to suppress proliferation of CD4 T cells and to induce FOXP3-expression in CD4 T cells, typical of regulatory T cells. No such findings were observed when using CD14+ HLA-DR+ monocytes. Moreover, MDSC depleted of CD16+ monocytes showed weaker immunosuppressive capacity. In patients with haemochromatosis, the frequency of CD14+ HLA-DR– MDSC in peripheral blood ranged from 0·5% to 79% and in the liver of cirrhotic patients from 9·1% to 75·5%.InterpretationCD14+ HLA-DR– MDSC are fully functional in patients who have non-infectious or non-malignant liver disease. Similar to HLA-DR+ monocytes, CD16 expression may identify subtypes of monocytic MDSC with distinct immunoregulatory properties. Given the varying frequency of MDSC in the patients analysed, the clinical relevance of MDSC in non-malignant and non-infectious liver-disease has to be further analysed since they may influence the course of disease in these patients.FundingDeutsche Forschungsgemeinschaft and Liver Foundation Trust Fund.     

Prescribing patterns of psychotropic medications in psychiatric disorders: a descriptive study from Palestine

International Journal of Clinical Pharmacy - Background The practice patterns of psychiatrists have changed over the last two decades. Objectives This study describes the pattern of prescribing...     

Anti-allergic drugs and the Annexin-A1 system

This paper, which was presented at the 17th JMRC ‘John Robert Vane Memorial’ Symposium, describes some recent work from the authors’ laboratory that provides a tentative explanation for the anti-inflammatory effects produced by the cromoglycate-like antiallergic drugs. Some of the implications of this finding are discussed.     

Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.     

The costs of traumatic brain injury due to motorcycle accidents in Hanoi, Vietnam

Background

Road traffic accidents are the leading cause of fatal and non-fatal injuries in Vietnam. The purpose of this study is to estimate the costs, in the first year post-injury, of non-fatal traumatic brain injury (TBI) in motorcycle users not wearing helmets in Hanoi, Vietnam. The costs are calculated from the perspective of the injured patients and their families, and include quantification of direct, indirect and intangible costs, using years lost due to disability as a proxy.

Methods

The study was a retrospective cross-sectional study. Data on treatment and rehabilitation costs, employment and support were obtained from patients and their families using a structured questionnaire and The European Quality of Life instrument (EQ6D).

Results

Thirty-five patients and their families were interviewed. On average, patients with severe, moderate and minor TBI incurred direct costs at USD 2,365, USD 1,390 and USD 849, with time lost for normal activities averaging 54 weeks, 26 weeks and 17 weeks and years lived with disability (YLD) of 0.46, 0.25 and 0.15 year, respectively.

Conclusion

All three component costs of TBI were high; the direct cost accounted for the largest proportion, with costs rising with the severity of TBI. The results suggest that the burden of TBI can be catastrophic for families because of high direct costs, significant time off work for patients and caregivers, and impact on health-related quality of life. Further research is warranted to explore the actual social and economic benefits of mandatory helmet use.