Experimental validation of a novel method of dose accumulation for the rectum.

BACKGROUND: Dose-surface maps (DSMs) are an increasingly popular tool to evaluate spatial dose-outcome relationships for the rectum. Recently, DSM addition has been proposed as an alternative method of dose accumulation from deformable registration-based techniques. In this study, we performed the first experimental investigation of the accuracy at which DSM accumulation can capture the total dose delivered to a rectum's surface in the presence of inter-fraction motion. MATERIAL AND METHODS: A custom PVC rectum phantom capable of representing typical rectum inter-fraction motion and filling variations was constructed for this project. The phantom allowed for the placement of EBT3 film sheets on the representative rectum surface to measure rectum surface dose. A multi-fraction prostate VMAT treatment was designed and delivered to the phantom in a water tank for a variety of inter-fraction motion scenarios. DSMs for each fraction were calculated in two ways using CBCT images acquired during delivery and summed to produce accumulated DSMs. Accumulated DSMs were then compared to film measurements using gamma analysis (3%/2 mm criteria). Similarity of isodose clusters between films and DSMs was also investigated. RESULTS: Baseline agreement between film measurements and accumulated DSMs for a stationary rectum was 95.6%. Agreement between film and accumulated DSMs in the presence of different types of inter.-fraction motion was ≥92%, and isodose cluster mean distance to agreement was within 1.5 mm for most scenarios. Overall, DSM accumulation performed the best when using DSMs that accounted for changes in rectum path orientation. CONCLUSION: Dose accumulation performed with DSMs was found to accurately replicate total delivered dose to a rectum phantom in the presence of inter-fraction motion.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

A systematic review of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds.

BACKGROUND: Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds. OBJECTIVE: To evaluate the available literature on the efficacy and safety of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds in humans. METHODS: A systematic review of the literature utilizing MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify published clinical trials of autologous adipose-derived SVF or similar ADSC-containing derivatives for patients with acute cutaneous wounds. This was supplemented by searches for ongoing clinical trials through ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. RESULTS: 872 records were initially retrieved. Application of inclusion and exclusion criteria yielded 10 relevant studies: two completed non-randomized controlled trials and eight ongoing clinical trials. Both completed studies reported a statistically significant benefit in percentage re-epithelialization and time to healing for the SVF treatment arms. Safety information for SVF was not provided. Ongoing clinical trials were assessing outcomes such as safety, patient and observer reported scar appearance, wound healing rate, and wound epithelization. CONCLUSION: In the context of substantial limitations in the quantity and quality of available evidence, the existing literature suggests that SVF may be a useful treatment for acute cutaneous wounds in humans. More clinical trials with improved outcome measures and safety assessment are needed.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Novel therapeutic strategies targeting telomere maintenance mechanisms in high-risk neuroblastoma.

The majority of high-risk neuroblastomas can be divided into three distinct molecular subgroups defined by the presence of MYCN amplification, upstream TERT rearrangements or alternative lengthening of telomeres (ALT). The common defining feature of all three subgroups is altered telomere maintenance; MYCN amplification and upstream TERT rearrangements drive high levels of telomerase expression whereas ALT is a telomerase independent telomere maintenance mechanism. As all three telomere maintenance mechanisms are independently associated with poor outcomes, the development of strategies to selectively target either telomerase expressing or ALT cells holds great promise as a therapeutic approach that is applicable to the majority of children with aggressive disease.Here we summarise the biology of telomere maintenance and the molecular drivers of aggressive neuroblastoma before describing the most promising therapeutic strategies to target both telomerase expressing and ALT cancers. For telomerase-expressing neuroblastoma the most promising targeted agent to date is 6-thio-2'-deoxyguanosine, however clinical development of this agent is required. In osteosarcoma cell lines with ALT, selective sensitivity to ATR inhibition has been reported. However, we present data showing that in fact ALT neuroblastoma cells are more resistant to the clinical ATR inhibitor AZD6738 compared to other neuroblastoma subtypes. More recently a number of additional candidate compounds have been shown to show selectivity for ALT cancers, such as Tetra-Pt (bpy), a compound targeting the telomeric G-quadruplex and pifithrin-α, a putative p53 inhibitor. Further pre-clinical evaluation of these compounds in neuroblastoma models is warranted.In summary, telomere maintenance targeting strategies offer a significant opportunity to develop effective new therapies, applicable to a large proportion of children with high-risk neuroblastoma. In parallel to clinical development, more pre-clinical research specifically for neuroblastoma is urgently needed, if we are to improve survival for this common poor outcome tumour of childhood.

Video education to improve recognition of common benign and malignant cutaneous lesions and skin cancer prevention in the public.

OBJECTIVE: Although dermatologists strive to provide patient education on sun protection and skin cancer, approximately 90% of Americans have limited health literacy skills. Little has been written about the means to best teach all levels of learners to recognize common benign and malignant skin lesions. Earlier work found that with advancing age, adults were less able to identify concerning lesions, thus underscoring the need for accessible education. METHODS: We showed subjects a brief video (7th grade level) about common cutaneous growths, reducing the risk of skin cancer, and the importance of early detection. Subjects were asked about their skin cancer history, educational format preference, and the perceived impact of the video. Comprehension of symptoms of skin cancer and the benefits of sunscreen use and the ability to identify a melanoma, nevus, angioma, and seborrheic keratosis were also assessed. RESULTS: Of the 156 subjects, mean age 52.7 years (range, 18-88 years), 31% had a history of skin cancer. A total of 98.7% found the video to be helpful; 92% preferred having a video as part of their teaching versus 9% who preferred written materials alone, 99% knew that a new or changing lesion could signal skin cancer, and 100% correctly answered that wearing sunscreen is protective. Subjects correctly identified lesions as melanoma (99%), benign mole (97%), angiomas (96%), and seborrheic keratosis (91%). There was a nominal trend toward higher scores in people who preferred video learning, had no history of skin cancer, and were older than 60 years of age. CONCLUSION: In this study, we found that a brief, plain-language video was effective at conveying understandable content to help subjects learn to identify common cancerous and benign skin growths while also teaching them strategies to protect against skin cancer.

Translation of the Diabetes Prevention Program for diabetes risk reduction in Chinese immigrants in New York City.

AIMS: To evaluate the effectiveness and feasibility of implementing a linguistically and culturally tailored Diabetes Prevention Program among Chinese immigrants with prediabetes living in New York City. METHODS: A total of 60 Chinese immigrants with prediabetes were randomized into either a Diabetes Prevention Program lifestyle intervention (n = 30) consisting of 12 bi-weekly core sessions and six monthly post-core sessions or the control intervention (n = 30), consisting of quarterly mailing of diabetes prevention information. Each Diabetes Prevention Program intervention session lasted 1.5-2 h and covered topics such as healthy eating, physical activity, stress reduction and problem-solving skills. Outcomes such as percent change in weight, BMI, and HbA1c concentration were assessed at baseline, 6 and 12 months. A mixed-effects linear regression was applied to test the intervention effect at months 6 and 12. Data were collected in the period 2012-2013 and analysed in 2014. RESULTS: The participant attrition rate was < 5% (2 out of 60) at 12 months. There was a significantly greater percent weight loss in the intervention group (-3.5 vs. -0.1%; P = 0.0001) at 6 months, which was largely maintained at 12 months (-3.3 vs. 0.3%; P = 0.0003). CONCLUSIONS: Participants in a Diabetes Prevention Program-based intervention achieved greater weight loss and improvements in HbA1c concentration than control participants. Evaluation of the Chinese Diabetes Prevention Program curriculum in a larger trial is warranted.

Nitric Oxide-cGMP-PKG Pathway Acts on Orai1 to Inhibit the Hypertrophy of Human Embryonic Stem Cell-Derived Cardiomyocytes.

Cardiac hypertrophy is an abnormal enlargement of heart muscle. It frequently results in congestive heart failure, which is a leading cause of human death. Previous studies demonstrated that the nitric oxide (NO), cyclic GMP (cGMP), and protein kinase G (PKG) signaling pathway can inhibit cardiac hypertrophy and thus improve cardiac function. However, the underlying mechanisms are not fully understood. Here, based on the human embryonic stem cell-derived cardiomyocyte (hESC-CM) model system, we showed that Orai1, the pore-forming subunit of store-operated Ca(2+) entry (SOCE), is the downstream effector of PKG. Treatment of hESC-CMs with an α-adrenoceptor agonist phenylephrine (PE) caused a marked hypertrophy, which was accompanied by an upregulation of Orai1. Moreover, suppression of Orai1 expression/activity using Orai1-siRNAs or a dominant-negative construct Orai1(G98A) inhibited the hypertrophy, suggesting that Orai1-mediated SOCE is indispensable for the PE-induced hypertrophy of hESC-CMs. In addition, the hypertrophy was inhibited by NO and cGMP via activating PKG. Importantly, substitution of Ala for Ser(34) in Orai1 abolished the antihypertrophic effects of NO, cGMP, and PKG. Furthermore, PKG could directly phosphorylate Orai1 at Ser(34) and thus prevent Orai1-mediated SOCE. Together, we conclude that NO, cGMP, and PKG inhibit the hypertrophy of hESC-CMs via PKG-mediated phosphorylation on Orai1-Ser-34. These results provide novel mechanistic insights into the action of cGMP-PKG-related antihypertrophic agents, such as NO donors and sildenafil.

Emergency medicine resident physicians' perceptions of electronic documentation and workflow: a mixed methods study.

OBJECTIVE: To understand emergency department (ED) physicians' use of electronic documentation in order to identify usability and workflow considerations for the design of future ED information system (EDIS) physician documentation modules. METHODS: We invited emergency medicine resident physicians to participate in a mixed methods study using task analysis and qualitative interviews. Participants completed a simulated, standardized patient encounter in a medical simulation center while documenting in the test environment of a currently used EDIS. We recorded the time on task, type and sequence of tasks performed by the participants (including tasks performed in parallel). We then conducted semi-structured interviews with each participant. We analyzed these qualitative data using the constant comparative method to generate themes. RESULTS: Eight resident physicians participated. The simulation session averaged 17 minutes and participants spent 11 minutes on average on tasks that included electronic documentation. Participants performed tasks in parallel, such as history taking and electronic documentation. Five of the 8 participants performed a similar workflow sequence during the first part of the session while the remaining three used different workflows. Three themes characterize electronic documentation: (1) physicians report that location and timing of documentation varies based on patient acuity and workload, (2) physicians report a need for features that support improved efficiency; and (3) physicians like viewing available patient data but struggle with integration of the EDIS with other information sources. CONCLUSION: We confirmed that physicians spend much of their time on documentation (65%) during an ED patient visit. Further, we found that resident physicians did not all use the same workflow and approach even when presented with an identical standardized patient scenario. Future EHR design should consider these varied workflows while trying to optimize efficiency, such as improving integration of clinical data. These findings should be tested quantitatively in a larger, representative study.

ALGEBRA: ALgorithm for the heterogeneous dosimetry based on GEANT4 for BRAchytherapy.

Task group 43 (TG43)-based dosimetry algorithms are efficient for brachytherapy dose calculation in water. However, human tissues have chemical compositions and densities different than water. Moreover, the mutual shielding effect of seeds on each other (interseed attenuation) is neglected in the TG43-based dosimetry platforms. The scientific community has expressed the need for an accurate dosimetry platform in brachytherapy. The purpose of this paper is to present ALGEBRA, a Monte Carlo platform for dosimetry in brachytherapy which is sufficiently fast and accurate for clinical and research purposes. ALGEBRA is based on the GEANT4 Monte Carlo code and is capable of handling the DICOM RT standard to recreate a virtual model of the treated site. Here, the performance of ALGEBRA is presented for the special case of LDR brachytherapy in permanent prostate and breast seed implants. However, the algorithm is also capable of handling other treatments such as HDR brachytherapy.

SU-E-J-208: Dosimetric Assessment of Treatment Using CBCT Images.

PURPOSE: To evaluate target coverage for five breast patients receiving boost treatment to the tumor bed by calculating the daily dose on cone beam computed tomography (CBCT) images and utilizing deformable image registration techniques. METHODS: The daily dose is calculated on pretreatment CBCT images using the same beam configuration as the original volumetric modulated arc therapy (VMAT) plan. Calculations were done with two different isocenter positions according to: (1) the initial patient setup and (2) the shifts applied for treatment based on CBCT verification. The daily doses are deformed and accumulated onto the planning CT using commercially available deformable image registration software. The dose distribution is compared to the original distribution and tumor and PTV coverage is evaluated for both situations (initial and shifted positions). The deformation accuracy is evaluated by calculating the change in centroid location and the Dice coefficient of deformed contours. RESULTS: The tumor bed is adequately covered regardless of the treatment position. The average dose received by 98% (D98) of the tumor bed volume differs from the original plan by +1.6% and -0.2% for the shifted and initial positions respectively. However, when dose is accumulated in the initial setup position PTV coverage is lost; the average D98 for the PTV changes by -15.8% and -26.9% for the shifted and initial positions respectively. The average change in centroid location is 0.43 mm and 1.53 mm for the left and right lung contour respectively. The Dice coefficient for the left and right lung is 0.94 and 0.95 respectively. CONCLUSIONS: The margins used to define the PTV are sufficient to ensure tumor bed coverage for the given positioning variability. We are also confident in the deformation used to deform and accumulate dose based on deformed contour comparison. Hardware provided by MIM Software Inc.

ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin.

The ATP-binding cassette G2 (ABCG2) c.421C>A (rs2231142) polymorphism influences the pharmacokinetics of rosuvastatin. We examined whether this polymorphism influences the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of the drug. In 305 Chinese patients with hypercholesterolemia who were treated with rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be significantly associated with greater reduction in LDL-C level, in a gene-dose-dependent manner. As compared with subjects with the c.421CC genotype, those with the c.421AA genotype showed a 6.9% greater reduction in LDL-C level, which would be equivalent to the effect obtained by doubling the dose of rosuvastatin.

Monte Carlo study of LDR seed dosimetry with an application in a clinical brachytherapy breast implant.

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.

Sci-Sat AM(2): Brachy-08: Monte Carlo calculations of 192Ir high dose rate brachytherapy treatment plans using CT and cone beam CT images.

The feasibility of using cone beam computed tomography (CBCT) images for Monte Carlo (MC) brachytherapy dose calculations has been investigated. To evaluate the effects of tissue heterogeneities and finite patient dimensions for 192Ir high dose rate treatment, CT-based MC calculations for breast and head and neck cases were first performed using the PTRAN_CT photon transport code. PTRAN_CT is an accelerated MC code specifically designed for patient-specific dose calculations. Muscles and adipose tissues, which are nearly indistinguishable in CBCT images, are found to cause minimal dose perturbations at 192Ir energies compared to water. The proximity of the tumor to the skin, however, will have an observable impact on the dose up to a few percent. Therefore, for CBCT calculations, a reasonable assignment of material and density values to the patient voxel geometry, with a good delineation of the skin and bony structures, will suffice for MC dose calculations. A CBCT-based calculation for an actual treatment plan with the tumor close to the cheek was performed. The results were compared to TG43 calculations to quantify the dose differences in the target and critical structures. Since the dose delivered to the tumor is mostly primary dose, deviations are found mostly in the organs at risk where scatter contribution becomes more significant. This study shows that for HDR brachytherapy applications, CBCT-based MC calculations is a feasible option despite inferior image quality and larger uncertainties in the Hounsfield Units compared to CT images. Research supported by Nucletron BV.

Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two iodine seeds in LDR brachytherapy.

PURPOSES: This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model seed. MATERIALS & METHODS: Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post-implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG-43 approximation effects were studied for a prostate and breast post-implant. RESULTS AND DISCUSSION: The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post-implant studies, a 10% difference between MC calculations and the TG-43 is found for both models of seeds. CONCLUSION: This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post-implant treatments.

Sci-Sat AM(2): Brachy-04: Spectral and dosimetric study of the Xoft electronic brachytherapy system.

The Axxent developed by Xoft Inc. is a miniature x-ray tube capable of generating a 50 kVp x-ray spectrum with dose-rates suitable for HDR applications. Results of spectral measurements compared with Geant4 Monte Carlo simulations have been published. This study is a continuation of previous work with shifting emphasis towards dosimetric characterization of the miniature x-ray tube. Dose distributions using EBT Gafchromic films agree to within 10 % of Geant4 results. In addition, TG-43 parameters can be calculated. However, consideration should be given to the biological effectiveness of the spectrum at different depths. Spectral measurements show significant beam hardening with 1st HVL increasing from 0.55 to 1.20 mm Al after 11.50 mm of water filtration. This effect may be attributed to the significant loss of low energy characteristic photons. Furthermore, the degree of beam hardening is dependent of the material, with 1st HVLs of 1.20 and 1.03 mm Al after 11.50 mm of water and Lucite respectively. The biological effect is quantified by calculating the number of single and double strand breaks. The number of strand breaks for the 50 kVp x-ray spectrum is similar to that of I-125 radiation.

Outpatient parenteral antibiotic therapy in Singapore.

Outpatient parenteral antibiotic therapy (OPAT) remains in its infancy in Singapore, with the first patients enrolled 4 years ago. Singapore's three largest hospitals, with over 3000 inpatient beds, now have designated and approved OPAT services. This study reviews the demographic, clinical and cost data of all patients enrolled in 2005 to facilitate benchmarking between services in Singapore and abroad and also to identify common needs for further development. In 2005, 225 OPAT enrollments in 208 different patients resulted in 4050 days of OPAT care. Orthopaedic diagnoses constituted 40% of admissions. Vancomycin was the most frequently used antibiotic (34%). The re-admission rate was 8.9%, but complications of OPAT care were only occasionally implicated. An estimated $207,200 was saved by patients despite there being significant financial disincentives to subsidised patients. OPAT is a safe, cost-efficient system that is becoming increasingly accepted in Singapore by patients, clinicians and management. Our three services have evolved independently into very similar practices. There is potential for further innovation, including outreach and carer-delivered dosing. However, major financial disincentives require review.

Association of lipoprotein lipase S447X, apolipoprotein E exon 4, and apoC3 -455T>C polymorphisms on the susceptibility to diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. In DN patients, triglyceride (TG) level is elevated and lipoprotein lipase (LPL) activity, which hydrolyzes TG, is decreased. The LPL S447X and apolipoprotein E (APOE) exon 4 polymorphisms affect TG levels, and the APOC3 -455T>C polymorphism affects LPL activity. Our aim was to examine the association of these polymorphisms with nephropathy in type 2 diabetes. We examined these polymorphisms in a case-control study of type 2 diabetic patients including 374 with DN and 392 without DN. LPL 447X-containing genotypes (447X+) were significantly decreased in DN patients [18.6 vs 25.6%, odds ratio (OR) = 0.66, p = 0.02], as were APOE epsilon3/epsilon3 genotypes (64.8 vs 73.1%, OR = 0.68, p = 0.01). In addition, combinations of genotypes [APOE epsilon3/epsilon3 and LPL 447X+ (OR = 0.56), APOC3 CC and LPL 447X+ (OR = 0.31), APOE epsilon3/epsilon3 and APOC3 CC (OR = 0.61] were protective for DN compared with the most common combination of the respective polymorphisms. Our findings suggest the importance of interactions among lipid genes in modulating the risk of DN.