Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system

Purpose: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac.

Methods and Materials: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan.

Results: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam.

Conclusions: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac. © 2014.

Implementation of phantom-less IMRT delivery verification using Varian DynaLog files and R/V output

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at -0.03-0.12 mm for prostate and -0.02-0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis.

Neutrophil elastase (NE) is thought to be the most important protease which damages the cystic fibrosis (CF) lung. Attempts have been made to suppress this activity using the plasma-derived inhibitor, alpha1-antitrypsin (AAT). In this pilot study, the safety and efficacy of inhaled recombinant human AAT (rAAT) as a treatment for CF were investigated. Thirty-nine patients participated in a prospective, double-blinded, randomized, placebo-controlled phase II trial to examine the effect of rAAT (500, 250, and 125 mg) on sputum NE activity. Sputum myeloperoxidase (MPO), interleukin-8, tumor necrosis factor receptors, sputum and plasma NE/AAT complexes, and safety parameters were also measured. Subjects were randomized to receive nebulized treatment once a day for 4 weeks, followed by 2–4 weeks with no study treatment, and then a 2-week rechallenge phase. Trends toward a reduction in NE activity were observed in patients treated with 500 mg and 250 mg of rAAT compared to placebo. Sputum NE/AAT complex and MPO levels were lower on rAAT compared to placebo. No major adverse events and, in particular, no allergic reactions to rAAT were observed. Although significant differences between rAAT and placebo for sputum NE activity were not observed, some improvements were found for secondary efficacy variables. This study demonstrated that nebulized rAAT is safe and well-tolerated, but has a limited effect on NE activity and other markers of inflammation. Pediatr Pulmonol.

Efficacy and safety of adjunctive mitomycin C during Ahmed Glaucoma Valve implantation:A prospective randomized clinical trial

Purpose To evaluate the efficacy and safety of intraoperative mitomycin C (MMC) in eyes undergoing Ahmed Glaucoma Valve implantation. Design Randomized controlled clinical trial. Participants Sixty patients with refractory glaucoma. Intervention Sixty eyes of 60 patients with refractory glaucoma were randomized to receive intraoperative MMC (0.5 mg/ml for 5 minutes) (n = 34) or balanced salt solution (n = 26) during Ahmed Glaucoma Valve implantation. Main outcome measures Surgical success was defined according to 2 different criteria: (1) postoperative intraocular pressure (IOP) between 6 and 21 mmHg, with or without antiglaucoma medications, and (2) IOP reduction of at least 30% relative to preoperative values. Eyes requiring additional glaucoma surgery, developing phthisis, or showing loss of light perception were classified as failures. Success rates in both groups were compared using Kaplan-Meier survival curves and the log rank test. Other outcome measures were mean IOP, number of glaucoma medications, and complications. Results After a mean follow-up of 12.3 months, Kaplan-Meier survival analysis showed a probability of success of 59% at 18 months for the MMC group and 61% for the control group when the first criterion for success was used (IOP between 6 and 21 mmHg). When an IOP reduction of at least 30% was used as the criterion to define success, the Kaplan-Meier survival analysis demonstrated a probability of success at 18 months of 62% for the MMC group and 67% for the control group. There were no significant differences in survival rates between the 2 groups with either criterion (P = 0.75 and P = 0.37, respectively). After 15 days postoperatively, the mean IOP did not significantly differ for both MMC and control eyes. Mean numbers of postoperative antiglaucoma medications were similar in MMC-treated eyes and controls. There was no significant difference between the incidences of postoperative complications in both groups. Conclusion Mitomycin C did not increase the short- or intermediate-term success rates of Ahmed Glaucoma Valve implantation. © 2004 by the American Academy of Ophthalmology.

Safety and Immunogenicity of a Novel Recombinant Subunit Respiratory Syncytial Virus Vaccine (BBG2Na) in Healthy Young Adults

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 μg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-μg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced ⩾2-fold and ⩾4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A–specific responses were 89% and 67%. Furthermore, up to 71% of subjects had ⩾2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults

Safety and Pharmacokinetics of Dapivirine Delivery From Matrix and Reservoir Intravaginal Rings to HIV-Negative Women

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twentyfour
healthy HIV-negative women 18–35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma
and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were ,2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

Creating Safety for Trauma Survivors: What can Therapists do?

This paper serves as a reminder to those working clinically in the field of trauma of the necessity for therapists to adequately include issues of safety within the therapeutic process. Addressing these issues is an integral part of the therapy and not simply a practical prerequisite or a parallel process. Validation of this thesis is drawn from trauma literature and an account of safety issues relating to the therapeutic setting and processes is given. Case examples illustrate the type of issues that might usefully be addressed within the therapeutic context to increase individual and family safety for clients as they continue to live within their local communities. This paper draws on recent work undertaken at the Family Trauma Centre. This Centre, based in South Belfast, is in its second year of operation. The Family Trauma Centre has a primary remit to provide clinical treatment for children and their families suffering from the traumatic effects of the ‘Troubles’ in Northern Ireland. The community context for this work has been one of continuous low-grade conflict in the midst of a ‘Peace’ process.

Experiences with mephedrone pre- and post-legislative controls: Perceptions of safety and sources of supply

Background: Drug scenes within several countries have changed in recent years to incorporate a range of licit psychoactive products, collectively known as “legal highs.” Hundreds of different legal high products have been described in the literature. Many of these products contain synthetic stimulants that allegedly
“mirror” the effects of some illicit drugs. In 2009–2010, growing concern by the UK and Irish governments focused on mephedrone, a synthetic stimulant that had become embedded within several drug scenes in Britain and Ireland. In April 2010, mephedrone and related cathinone derivatives were banned under
the UK’s Misuse of Drugs Act 1971. Setting aside “worse case scenarios” that have been portrayed by UK and Irish media, little is known about mephedrone use from the consumer’s perspective. The purpose of this paper was to (1) explore respondents’ experiences with mephedrone, (2) examine users’ perceptions
about the safety of mephedrone, and primarily to (3) examine sources of mephedrone supply during the pre- and post-ban periods.
Methods: Semi-structured interviews were conducted with 23 adults who had used mephedrone during 2009–2010. Data collection occurred in May and June 2010, following the ban on mephedrone. A total of 20/23 respondents had used mephedrone during the post-ban period, and the vast majority had prior
experience with ecstasy or cocaine. Respondents’ ages ranged from 19 to 51, approximately half of the sample were female and the majority (19 of 23) were employed in full- or part-time work.
Results: Most respondents reported positive experiences with mephedrone, and for some, the substance emerged as a drug of choice. None of the respondents reported that the once-legal status of mephedrone implied that it was safe to use. Very few respondents reported purchasing mephedrone from street-based
or on-line headshops during the pre-ban period, and these decisions were guided in part by respondents’ attempts to avoid “drug user” identities. Most respondents purchased or obtained mephedrone from friends or dealers, and mephedrone was widely available during the 10-week period following the ban. Respondents reported a greater reliance on dealers and a change in mephedrone packaging following the criminalisation of mephedrone.
Conclusion: The findings are discussed in the context of what appears to be a rapidly changing mephedrone market. We discuss the possible implications of criminalising mephedrone, including the potential displacement effects and the development of an illicit market.

Confined Site Construction: Issues Regarding Implementation of Health and Safety

The objective of this paper is to identify the various managerial constraints, difficulties and issues encountered and resulting strategies adopted, to aid in the management of the various and often complex health and safety concerns, which occur within a confined construction site. This is achieved through classifying the various managerial burdens encountered with the numerous strategies adopted, to ensure the successful management of such confined environments within the realm of health and safety. Through an extensive literature review and detailed interviews, a comprehensive insight into the health and safety concerns within a confined construction site environment is portrayed. The leading managerial strategies to the management of health and safety on confined construction sites may be listed as follows; (1) Traffic Management Plan, (2) Effective Resource Management Plan, (3) Temporary Facilities Management Plan, (4) Safe System of Work Plan, (5) Site Safety Plan, (6) Design Site Layout, (7) Space Management Plan, (8) Effective Program Management, and (9) Space Scheduling. Based on the research, it can be concluded, that through effective management of these issues identified coupled with implementing the various strategies highlighted; successful management of health and safety within a confined construction site environment is attainable.

Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining inter-individual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children.

Confined site construction: A qualitative review of issues regarding health and safety on-site

The construction industry is inherently hazardous, with a significant number of accidents and incidents occurring, particularly on confined construction sites. This research identifies, clarifies and tabulates the various managerial health and safety issues encountered on confined construction sites, based on a qualitative approach, to aid in the management of the complex health and safety concerns. The methodology is based on qualitative research incorporating case studies, interviews, causal loop diagrams and mind mapping. The key findings in the managerial issues in the management of health and safety on confined construction sites can be summarised as follows; (1) A lack of space, (2) Increased management of site personnel, (3) Overcrowding of the work place. The implication for the industry is that due to the sustained development of urban centres on a global scale, coupled with the increasing complexity of architectural designs, the majority of on-site project management professionals are faced with the onerous task of completing often intricate designs within a limited spatial environment, under strict health and safety parameters. The value of such research is to aid management professionals successfully identify the various managerial issues highlighted, resulting in the successful management of health and safety on a confined construction site.