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Purpose Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m‐bm) when using single‐isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT‐VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. Material and Methods Nine complex patients with 61 total tumors (2‐16 tumors/patient) were planned using SIMT‐VMAT with geometry similar to HyperArc with a 10MV‐FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m‐bm via SIMT‐VMAT. Results Patient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. Conclusions Radiosurgery of m‐bm using SIMT‐VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation‐induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m‐bm using a SIMT‐VMAT plan.

Purpose To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge‐based planning (KBP) model to support offline adaptive radiotherapy. Materials/methods Twenty previously treated non‐coplanar volumetric‐modulated arc therapy (VMAT) lung SBRT plans (c‐Truebeam) on SBRT‐dedicated C‐arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c‐Truebeam plans were re‐optimized for Halcyon manually (m‐Halcyon) and with KBP model (k‐Halcyon). Both m‐Halcyon and k‐Halcyon plans were normalized for identical or better target coverage than clinical c‐Truebeam plans and compared for target conformity, dose heterogeneity, dose fall‐off, and dose tolerances to the organs‐at‐risk (OAR). Treatment delivery parameters and planning times were evaluated. Results k‐Halcyon plans were dosimetrically similar or better than m‐Halcyon and c‐Truebeam plans. k‐Halcyon and m‐Halcyon plan comparisons are presented with respect to c‐Truebeam. Differences in conformity index were statistically insignificant in k‐Halcyon and on average 0.02 higher (p = 0.04) in m‐Halcyon plans. Gradient index was on average 0.43 (p = 0.006) lower and 0.27 (p = 0.02) higher for k‐Halcyon and m‐Halcyon, respectively. Maximal dose 2 cm away in any direction from target was statistically insignificant. k‐Halcyon increased maximal target dose on average by 2.9 Gy (p

Synchronous treatment of two lung lesions using a single‐isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can decrease treatment time and reduce the impact of intrafraction motion. However, alignment of both lesions on a single cone beam CT (CBCT) can prove difficult and may lead to setup errors and unacceptable target coverage loss. A Restricted Single‐Isocenter Stereotactic Body Radiotherapy (RESIST) method was created to minimize setup uncertainties and provide treatment delivery flexibility. RESIST utilizes a single‐isocenter placed at patient’s midline and allows both lesions to be planned separately but treated in the same session. Herein is described a process of automation of this novel RESIST method. Automation of RESIST significantly reduced treatment planning time while maintaining the benefits of RESIST. To demonstrate feasibility, ten patients with two lung lesions previously treated with a single‐isocenter clinical VMAT plan were replanned manually with RESIST (m‐RESIST) and with automated RESIST (a‐RESIST). a‐RESIST method automatically sets isocenter, creates beam geometry, chooses appropriate dose calculation algorithms, and performs VMAT optimization using an in‐house trained knowledge‐based planning model for lung SBRT. Both m‐RESIST and a‐RESIST showed lower dose to normal tissues compared to manually planned clinical VMAT although a‐RESIST provided slightly inferior, but still clinically acceptable, dose conformity and gradient indices. However, a‐RESIST significantly reduced the treatment planning time to less than 20 min and provided a higher dose to the lung tumors. The a‐RESIST method provides guidance for inexperienced planners by standardizing beam geometry and plan optimization using DVH estimates. It produces clinically acceptable two lesions VMAT lung SBRT plans efficiently. We have further validated a‐RESIST on phantom measurement and independent pretreatment dose verification of another four selected 2‐lesions lung SBRT patients and implemented clinically. Further development of a‐RESIST for more than two lung lesions and refining this approach for extracranial oligometastastic abdominal/pelvic SBRT, including development of automated simulated collision detection algorithm, merits future investigation.

Stereotactic body radiotherapy (SBRT) of lung tumors via the ring‐mounted Halcyon Linac, a fast kilovoltage cone beam CT‐guided treatment with coplanar geometry, a single energy 6MV flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for selected lung cancer patients. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB algorithm with heterogeneity corrections using an SBRT board and Halcyon couch insert. Halcyon VMAT‐SBRT plans with stacked and staggered multileaf collimators produced highly conformal radiosurgical dose distribution to the target, lower intermediate dose spillage, and similar dose to adjacent organs at risks (OARs) compared to SBRT‐dedicated highly conformal clinical noncoplanar Truebeam VMAT plans following the RTOG‐0813 requirements. Due to low monitor units per fraction and less multileaf collimator (MLC) modulation, the Halcyon VMAT plan can deliver lung SBRT fractions with an overall treatment time of less than 15 min (for 50 Gy in five fractions), significantly improving patient comfort and clinic workflow. Higher pass rates of quality assurance results demonstrate a more accurate treatment delivery on Halcyon. We have implemented Halcyon for lung SBRT treatment in our clinic. We suggest others use Halcyon for lung SBRT treatments using abdominal compression or 4D CT‐based treatment planning, thus expanding the access of curative ultra‐hypofractionated treatments to other centers with only a Halcyon Linac. Clinical follow‐up results for patients treated on Halcyon Linac with lung SBRT is ongoing.

Treating multiple lung lesions synchronously via single‐isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance. However, aligning multiple lung tumors accurately on single pretreatment cone beam CTs (CBCTs) can be problematic. Tumors misaligned could lead to target coverage loss. To quantify this potential target coverage loss due to small, clinically realistic setup errors, a novel simulation method was developed. This method was used on 26 previously treated patients with two metastatic lung lesions. Patients were treated with 4D CT‐based, highly conformal noncoplanar VMAT plans (clinical VMAT) with 6MV‐flattening filter free (FFF) beam using AcurosXB dose calculation algorithm with heterogeneity corrections. A single isocenter was placed approximately between the lesions to improve patient convenience and clinic workflow. Average isocenter to tumor distance was 5.9 cm. Prescription dose was 54 Gy/50 Gy in 3/5 fractions. For comparison, a plan summation (simulated VMAT) was executed utilizing randomly simulated, clinically relevant setup errors, obtained from pretreatment setup, per treatment fraction, in Eclipse treatment planning system for each of the six degrees of freedom within ± 5.0 mm and ± 2°. Simulations yielded average deviations of 27.4% (up to 72% loss) (P

Purpose To develop a robust and adaptable knowledge‐based planning (KBP) model with commercially available RapidPlanTM for early stage, centrally located non‐small‐cell lung tumors (NSCLC) treated with stereotactic body radiotherapy (SBRT) and improve a patient's“simulation to treatment” time. Methods The KBP model was trained using 86 clinically treated high‐quality non‐coplanar volumetric modulated arc therapy (n‐VMAT) lung SBRT plans with delivered prescriptions of 50 or 55 Gy in 5 fractions. Another 20 independent clinical n‐VMAT plans were used for validation of the model. KBP and n‐VMAT plans were compared via Radiation Therapy Oncology Group (RTOG)–0813 protocol compliance criteria for conformity (CI), gradient index (GI), maximal dose 2 cm away from the target in any direction (D2cm), dose to organs‐at‐risk (OAR), treatment delivery efficiency, and accuracy. KBP plans were re‐optimized with larger calculation grid size (CGS) of 2.5 mm to assess feasibility of rapid adaptive re‐planning. Results Knowledge‐based plans were similar or better than n‐VMAT plans based on a range of target coverage and OAR metrics. Planning target volume (PTV) for validation cases was 30.5 ± 19.1 cc (range 7.0–71.7 cc). KBPs provided an average CI of 1.04 ± 0.04 (0.97–1.11) vs. n‐VMAT plan'saverage CI of 1.01 ± 0.04 (0.97–1.17) (P

The Atmospheric Effects of Precipitation through Energetic X-rays (AEPEX) mission is a 6U CubeSat that will monitor energetic electron precipitation from the radiation belts into the upper atmosphere. The primary instrument will image energetic (50–300 keV) X-rays produced in the atmosphere by bremsstrahlung, providing a near-direct signature of electron precipitation. An energetic electron detector will measure the precipitating electron spectrum, while the X-ray observations will be used to determine the absolute flux. X-ray images will be produced with 10-s time resolution and 50–100 km spatial resolution. The 6U spacecraft uses flight heritage spacecraft bus subsystems, including the attitude determination and control, electrical power, and command & data handling systems. AEPEX is designed to be operated from low-Earth orbit at ~ 500 km altitude with a high inclination in order to cover the outer radiation belt. AEPEX will be the first spacecraft mission to measure X-rays in the 50–300 keV energy range emitted by Earth’s atmosphere in response to radiation belt precipitation, and the first to image that precipitation from above.

Cone‐beam computed tomography (CT)‐guided volumetric‐modulated arc therapy (VMAT) plans for stereotactic body radiotherapy (SBRT) treatment of synchronous multiple lung lesions with a flattening filter‐free (FFF) beam is a safe and highly effective treatment option for oligometastases lung cancer patients. Fourteen patients with metastatic non–small‐cell lung cancer (NSCLC) lesions (two to five) received a single‐isocenter VMAT SBRT treatment in our clinic. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB‐based dose calculation algorithm using heterogeneity corrections with a single isocenter placed between/among the lesions. Compared to 10X‐FFF and traditional flattened 6X (6X‐FF) beams, 6X‐FFF beam produced highly conformal radiosurgical dose distribution to each target volume, reduced dose to adjacent organs at risk (OAR), and significantly reduced the lung SBRT fraction duration to

Cone‐beam CT‐guided single dose of lung stereotactic body radiotherapy (SBRT) treatment with a flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a safe and highly effective treatment modality for selective small lung lesions. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB algorithm for heterogeneity corrections. 6X‐FFF beam produced highly conformal radiosurgical dose distribution to the target and reduced lung SBRT fraction duration to less than 10 min for a single dose of 30 Gy, significantly improving patient comfort and clinic workflow. Early follow‐up CT imaging results (mean, 8 months) show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow‐up in a larger patient cohort managed in this fashion is underway to further validate this treatment approach.

The philosophy of patient-centred care has become widely embraced but its implementation is dependent on interrelated factors. A factor that has received limited attention is the role of policy tools. In Ontario, one method government can use to promote healthcare priorities is through health regulatory colleges, which set the standard of practice for health professionals. The degree to which government policy in support of patient-centered care has influenced the direction provided by health regulatory colleges to their members, and ultimately impacted actual patient care, remains unclear. This study investigates the extent to which Ontario's health regulatory colleges have provided explicit written guidance to members related to the importance of patient-centred care. It also explores applied and theoretical explanations that may further our understanding of why patient-centred care has not been more fully embraced. Findings reveal that guidance provided by Ontario's health regulatory colleges varies widely. Institutional barriers and the choice of policy tools for disseminating government preferences may hinder full implementation of the principles of patient-centred care. More fully understanding the role health regulatory colleges' play in facilitating the implementation of health policy will contribute positively to dialogue and to efforts to achieve positive health system reforms.

PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33–based high-intermediate–risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

BACKGROUND: Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence. METHODS: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life. RESULTS: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan–Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group. CONCLUSIONS: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.)

Recent disasters and health emergencies, including the COVID-19 pandemic, have shed light on the fragility of the U.S. medical supply chain and underscored the need to explore policy, regulatory, and systems solutions to prevent and mitigate the impacts of shortages on public health, national security, and patient care. Under the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the National Academies of Sciences, Engineering, and Medicine established an ad hoc committee to examine the security and resilience of the U.S. medical product supply chain. Specifically, the committee was asked to assess and evaluate the impact of U.S. dependence on critical drugs and devices sourced or manufactured outside the U.S. and provide recommendations to improve the resilience and address the vulnerabilities of the medical supply chain. On December 1 and 2, 2020, the Committee on Security of America's Medical Product Supply Chain held a two-day virtual public workshop focused on assessing lists of critical and essential medical products. The workshop sought to conceptually explore how critical and essential medical product lists are developed and used in practice. The committee's consensus study report will be available in 2022. This Proceedings of a Workshop-in Brief summarizes the discussions that occurred at the workshop. © by the National Academy of Sciences. All rights reserved.

Many medical services lack robust evidence of effectiveness and may therefore be considered “unnecessary” care. Proactively withdrawing resources from, or de-funding, such services and redirecting the savings to services that have proven effectiveness would enhance overall health system performance. Despite this, governments have been reluctant to discontinue funding of services once funding is in place. The focus of this study is to understand how the framing of an issue or problem influences government decision-making related to de-funding of medical services. To achieve this, a framework describing how problem frames, or explanatory naratives, influence government policy decisions was developed and applied to actual cases. The two cases selected were the Ontario government’s decisions to de-fund the drug Oxycontin and blood glucose test strips used by patients with diabetes. A qualitative content analysis of public discourse (political debate and media coverage) surrounding these two resource withdrawal examples was conducted and described using the framework. In the framework, government decision-making is a partial reflection of the visibility of the policy issue and complexity of the causal story told within a problem frame. By applying this framework and considering these two key characteristics of problem frames, we can better understand, and possibly predict, the shape and timing of government policy decisions to withdraw resources from medical services.

Single-isocenter volumetric modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) techniques to treat multiple brain metastases simultaneously can significantly improve treatment delivery efficiency, patient compliance, and clinic workflow. However, due to large number of brain metastases sharing the same MLC pair causing island blocking, there is higher low- and intermediate-dose spillage to the normal brain and higher dose to organs-at-risk (OAR). To minimize this problem and improve plan quality, this study proposes a dual-isocenter planning strategy that groups lesions based on hemisphere location (left vs right sided) in the brain parenchyma, providing less island blocking reducing the MLC travel distance. This technique offers simplified planning while also increasing patient comfort and compliance by allowing for large number of brain metastases to be treated in 2 groups. Seven complex patients with 5 to 16 metastases (64 total) were planned with a single-isocenter VMAT-SRS technique using a 10MV-FFF beam with a prescription of 20 Gy to each lesion. The isocenter was placed at the approximate geometric center of the targets. Each patient was replanned using the dual-isocenter approach, generating 2 plans and placing each isocenter at the approximate geometric center of the combined targets of each side with corresponding non-coplanar partial arcs. Compared to single-isocenter VMAT, dual-isocenter VMAT plans provided similar target coverage and dose conformity with less spread of intermediate dose to normal brain with reduction of dose to OAR. Reduction in total monitor units and beam on time was observed, but due to the second isocenter setup and verification, overall treatment time was increased. Dual-isocenter VMAT-SRS planning for multiple brain metastases is a simplified approach that provides superior treatment options for patient compliance who may not tolerate longer traditional treatment times as with individual isocenters to each target. This planning technique significantly reduces the amount of low- and intermediate-dose spillage, further sparing OAR and normal brain, potentially improving target accuracy though localization of left vs right-sided tumors for each isocenter set up.

Purpose A single-isocenter volumetric modulated arc therapy (VMAT) treatment to multiple brain metastatic patients is an efficient stereotactic radiosurgery (SRS) option. However, the current clinical practice of single-isocenter SRS does not account for patient setup uncertainty, which degrades treatment delivery accuracy. This study quantifies the loss of target coverage and potential collateral dose to normal tissue due to clinically observable isocenter misalignment. Methods and materials Nine patients with 61 total tumors (2-16 tumors/patient) who underwent Gamma Knife® SRS were replanned in Eclipse™ using 10 megavoltages (MV) flattening-filter-free (FFF) bream (2400 MU/min), using a single-isocenter VMAT plan, similar to HyperArc™ VMAT plan. Isocenter was placed in the geometric center of the tumors. The prescription was 20 Gy to each tumor. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02-11.5 cc) and 1.9 cc (0.11-18.8 cc), respectively, derived from MRI images. The average isocenter to tumor distance was 5.5 cm (1.6-10.1 cm). Six-degrees of freedom (6DoF) random and systematic residual set up errors within [±2 mm, ±2o] were generated using an in-house script in Eclipse based on our pre-treatment daily cone-beam CT imaging shifts and recomputed for the simulated VMAT plan. Relative loss of target coverage as a function of tumor size and distance to isocenter were evaluated as well as collateral dose to organs-at risk (OAR). Results The average beam-on time was less than six minutes. However, loss of target coverage for clinically observable setup errors were, on average, 7.9% (up to 73.1%) for the GTV (p < 0.001) and 21.5% for the PTV (up to 93.7%; p < 0.001). The correlation was found for both random and systematic residual setup errors with tumor sizes; there was a greater loss of target coverage for small tumors. Due to isocenter misalignment, OAR doses fluctuated and potentially receive higher doses than the original plan. Conclusion A single-isocenter VMAT SRS treatment (similar to HyperArc™ VMAT) to multiple brain metastases was fast with < 6 min of beam-on time. However, due to small residual set up errors, single-isocenter VMAT, in its current use, is not an accurate SRS treatment modality for multiple brain metastases. Loss of target coverage was statistically significant, especially for smaller lesions, and may not be clinically acceptable if left uncorrected. Further investigation of correction strategies is underway.

Background Terms used to describe government-led resource withdrawal from ineffective and unsafe medical services, including ‘rationing’ and ‘disinvestment’, have tended to be used interchangeably, despite having distinct characteristics. This lack of descriptive precision for arguably distinct terms contributes to the obscurity that hinders effective communication and the achievement of evidence-based decision-making. The objectives of this study are to (1) identify the various terms used to describe resource withdrawal and (2) propose definitions for the key or foundational terms, which includes a clear description of the unique characteristics of each. Methods This is a systematic qualitative synthesis of characteristics and terms found through a search of the academic and grey literature. This approach involved identifying commonly used resource withdrawal terms, extracting data about resource withdrawal characteristics associated with each term and conducting a comparative analysis by categorising elements as antecedents, attributes or outcomes. Results Findings from an analysis of 106 documents demonstrated that terms used to describe resource withdrawal are inconsistently defined and applied. The characteristics associated with these terms, mainly antecedents and attributes, are used interchangeably by many authors but are differentiated by others. Our analysis resulted in the development of a framework that organises these characteristics to demonstrate the unique attributes associated with each term. To enhance precision, these terms were classified as either policy options or patient health outcomes and refined definitions for rationing and disinvestment were developed. Rationing was defined as resource withdrawal that denies, on average, patient health benefits. Disinvestment was defined as resource withdrawal that results in, on average, improved or no change in health benefits. Conclusion Agreement on the definition of various resource withdrawal terms and their key characteristics is required for transparent government decision-making regarding medical service withdrawal. This systematic qualitative synthesis presents the proposed definitions of resource withdrawal terms that will promote consistency, benefit public policy dialogue and enhance the policy-making process for health systems.

Purpose To develop a knowledge‐based planning (KBP) routine for stereotactic body radiotherapy (SBRT) of peripherally located early‐stage non‐small‐cell lung cancer (NSCLC) tumors via dynamic conformal arc (DCA)‐based volumetric modulated arc therapy (VMAT) using the commercially available RapidPlanTM software. This proposed technique potentially improves plan quality, reduces complexity, and minimizes interplay effect and small‐field dosimetry errors associated with treatment delivery. Methods KBP model was developed and validated using 70 clinically treated high quality non‐coplanar VMAT lung SBRT plans for training and 20 independent plans for validation. All patients were treated with 54 Gy in three treatments. Additionally, a novel k‐DCA planning routine was deployed to create plans incorporating historical three‐dimensional‐conformal SBRT planning practices via DCA‐based approach prior to VMAT optimization in an automated planning engine. Conventional KBPs and k‐DCA plans were compared with clinically treated plans per RTOG‐0618 requirements for target conformity, tumor dose heterogeneity, intermediate dose fall‐off and organs‐at‐risk (OAR) sparing. Treatment planning time, treatment delivery efficiency, and accuracy were recorded. Results KBPs and k‐DCA plans were similar or better than clinical plans. Average planning target volume for validation was 22.4 ± 14.1 cc (7.1–62.3 cc). KBPs and k‐DCA plans provided similar conformity to clinical plans with average absolute differences of 0.01 and 0.01, respectively. Maximal doses to OAR were lowered in both KBPs and k‐DCA plans. KBPs increased monitor units (MU) on average 1316 (P

Purpose/objectives To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Materials/methods Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed dose. For comparison, two‐isocenter plans (isocenter placed centrally in each target) were retrospectively created. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were calculated. The normal lung V5, V10, V20, mean lung dose (MLD) and other organs at risk (OARs) doses were evaluated. Total number of monitor units (MUs), beam‐on time, and patient‐specific quality assurance (QA) results were recorded. Results The mean isocenter to tumor distance was 6.7 ± 2.3 cm. The mean combined PTV was 44.0 ± 23.4 cc. There was no clinically significant difference in CI, HI, GD, GI, D2cm, and V20 including most of the OARs between single‐isocenter and two‐isocenter lung SBRT plans, evaluated per RTOG guidelines. However, for single‐isocenter plans as the distance between the lesions increased, the V5, V10, and MLD increased, marginally. The total number of MUs and beam‐on time was reduced by a factor of 1.5 for a single‐isocenter plan compared to a two‐isocenter plan. The single‐isocenter/two‐lesions VMAT lung SBRT QA plans demonstrated an accurate dose delivery of 98.1 ± 3.2% for clinical gamma passing rate of 3%/3 mm. Conclusion The SBRT treatment of two peripherally located lung lesions with a centrally placed single‐isocenter was dosimetrically equivalent to two‐isocenter plans. Faster treatment delivery for single‐isocenter treatment can improve patient compliance and reduce the amount of intrafraction motion errors for well‐suited patients.

AIM Bronchiolitis is a common respiratory illness and is a leading cause of hospitalisation in infancy. We aimed to appraise three recent national bronchiolitis guidelines produced by the Australasian Paediatric Research in Emergency Departments International Collaborative, the National Institute for Health and Care Excellence in the UK and the American Academy of Pediatrics. METHODS A group of final-year medical students and one senior clinician used the AGREE II tool to appraise each guideline in two stages. First, two students appraised each guideline independently and presented their results. Second, two self-selected students met with the senior clinicians to review all scores to ensure completeness of the appraisal and consistency of AGREE II application. RESULTS The guidelines scored well overall, with particular strengths in the domains of clarity of presentation, scope and purpose and rigour of development. Comparison of the recommendations across each guideline demonstrated a high degree of consistency. Notable differences included recommendations for the role of palivizumab in prevention of bronchiolitis, the use of continuous pulse oximetry monitoring in the hospitalised patient and the value of respiratory virus testing. CONCLUSIONS Our appraisal of bronchiolitis guidelines from three high-income countries demonstrated that they were of high quality, with substantial areas of agreement. Most aspects of clinical practice should be uniform for this common paediatric condition. Areas of guideline weakness were in the domains of applicability and editorial independence. We identified three areas of controversy where further research is needed to support stronger evidence-based recommendations.

We aim to extract a universal law that governs the gravity wave manifestation in polar mesospheric clouds (PMCs). Gravity wave morphology and the clarity level of display vary throughout the wave population manifested by the PMC albedo data. Higher clarity refers to more distinct exhibition of the features, which often correspond to larger variances and a better-organized nature. A gravity wave tracking algorithm based on the continuous Morlet wavelet transform is applied to the PMC albedo data at 83 km altitude taken by the Aeronomy of Ice in the Mesosphere (AIM) Cloud Imaging and Particle Size (CIPS) instrument to obtain a large ensemble of the gravity wave detections. The horizontal wavelengths in the range of ∼ 20–60 km are the focus of the study. It shows that the albedo (wave) power statistically increases as the background gets brighter. We resample the wave detections to conform to a normal distribution to examine the wave morphology and display clarity beyond the cloud brightness impact. Sample cases are selected at the two tails and the peak of the normal distribution to represent the full set of wave detections. For these cases the albedo power spectra follow exponential decay toward smaller scales. The high-albedo-power category has the most rapid decay (i.e., exponent = −3.2) and corresponds to the most distinct wave display. The wave display becomes increasingly blurrier for the medium- and low-power categories, which hold the monotonically decreasing spectral exponents of −2.9 and −2.5, respectively. The majority of waves are straight waves whose clarity levels can collapse between the different brightness levels, but in the brighter background the wave signatures seem to exhibit mildly turbulent-like behavior.

PURPOSE/OBJECTIVE(S) Lung cancer patients with multiple oligometastases (< 5) lesions with associated co-morbidities may not retain their treatment position for the extended Stereotactic Body Radiotherapy (SBRT) treatment times with individual isocenters for each lesion due to distress or shortness of breath. SBRT of multiple lung lesions synchronously (in one course) using a single-isocenter volumetric arc therapy (VMAT) plan with flattening filter free (FFF) beam or tomotherapy will shorten treatment courses, improve patient comfort by reducing treatment time, and improve clinic efficiency. We report our early clinical results of treating oligometastatic lung disease with synchronous single-course lung SBRT. MATERIALS/METHODS Fifty-six patients with multiple oligometastatic lung lesions (two n = 51, three n = 4, five n = 1, total 119 lesions) were treated synchronously with either highly conformal single-isocenter non-coplanar VMAT-SBRT (49 patients) or tomotherapy (7 patients). The most common prescriptions were 50-55 Gy/5 fractions or 54 Gy/3 fractions prescribed to 70-80% isodose line. The VMAT-SBRT plans were calculated with an advanced dose calculation algorithm for 6 MV-FFF beam and tomotherapy used superposition/convolution algorithm (with 6MV) for heterogeneity corrections. All plans were evaluated with RTOG-0618/0813 criteria. Treatments were delivered every other day with daily cone beam-CT/MVCT guidance. Highly conformal SBRT treatments were delivered in less than 10 min per fraction, on average. Local control rates, radiation-induced pneumonitis and rib toxicity were determined. Mean follow up interval was 11.4 months (range, 2.1 to 35.3 months). RESULTS All plans met RTOG-0618/0813 requirements for target(s) coverage, dose to organs at risk including lung and ribs and all patients tolerated SBRT. Six patients died before follow up and five were lost to follow up. Five patients have initial post-treatment imaging pending. Of forty evaluable patients, all achieved complete response to SBRT in all lesions. However, 18 patients developed distant metastases. During the follow-up interval, almost 50% of the patients developed radiographic changes that were asymptomatic in nature, however no patient developed grade+2 (or higher) pneumonitis, had rib fracture or developed chest wall pain. CONCLUSION A single course of lung SBRT to synchronous multiple lung lesions using a single-isocenter VMAT plan or tomotherapy is feasible, fast, safe and highly effective, with promising early local control rates and no adverse pulmonary side effects or rib toxicity. Although 18 patients developed distant metastases, the local control achieved in the treated lesions could preserve the patient's quality of life or delay systemic therapy even in these patients. Longer clinical follow up is warranted and planned. AUTHOR DISCLOSURE L. Downes: None. D. Pokhrel: None. L. Critchfield: None. M.E. Bernard: None. M.E. Randall: None. R.C. McGarry: None.

PURPOSE/OBJECTIVE(S) To evaluate the feasibility, safety and efficacy of conebeam CT-guided MLC-based GRID therapy as a same day treatment procedure for large bulky masses. MATERIALS/METHODS Twenty-eight patients (12 head and neck, 6 pelvis muscle, 3 breast, 2 chest, 2 liver, 2 para-spinal mass and 1 right arm) with large tumors (range 6.5-13.0 cm) tumors were planned and treated using MLC-based 3D-GRID therapy on the same day as CT-simulation. Utilizing an in-house MLC algorithm, 120 Millennium leaves were fitted to gross tumor volume (GTV) to generate 1 cm diameter holes and 2 cm center-to-center distance (at isocenter). For a single-dose of 15 Gy, 3D MLC-based GRID plans were generated using 4 to 6 coplanar crossfire gantry angles at 60o spacing for differentially-weighted 6 and/or 10MV beams with advanced dose calculation algorithm, generating sieve-like dose channeling without post-processing the GRID-GTV contour-allowing for same day treatment. Dosimetric parameters evaluated included: peak-to-valley dose ratio (PVDR) = GTVD10%/GTVD90%, GTVD50%, mean GTV dose, skin dose and maximal dose to immediately adjacent critical organs. Treatment planning and delivery times and patient set up accuracy was recorded. RESULTS MLC-GRID plans showed excellent dose parameters with mean GTVD50% and mean GTV of 15 Gy being 7.6 ± 0.5 Gy (range 6.6-8.5 Gy) and 7.8 ± 0.4 Gy (range 7.2-8.9 Gy), respectively. Average PVDR was 3.1 ± 0.6 (range 2.7-4.6). Maximum and D5 cc of skin were 10.0 ± 3.2 Gy (range 5.5-13.1 Gy) and 6.6 ± 2.2 Gy (range 1.3-9.6 Gy), respectively. Maximal doses immediately adjacent critical organs were as follows: spinal cord < 3.5 Gy, larynx < 6.7 Gy, humeral head < 6.3 Gy, femoral head < 6.5 Gy, small bowel < 6.9 Gy. Planning time was typically an hour. Mean beam-on time was 3.31 ± 0.16 min (range 3.11-3.54 min) and mean treatment time, including patient set up and conebeam CT imaging to beam-off, was 11.35 ± 0.21 min (range 11.11-11.56 min). Average 3-dimentional vector couch correction was (from the skin-marker) 0.49 ± 0.22 cm (range 0.18-0.88 cm). CONCLUSION The 3D MLC-based forward planned GRID therapy enhanced target dose for bulky masses including deep-seated large tumors while protecting skin and adjacent critical organs. This same day MLC-GRID treatment provides safe, effective, and convenient treatment by eliminating the risk to therapists and patient of heavy gantry-mounted physical GRID-block. This rapid 3D MLC-GRID planning and treatment can be easily adopted by any radiation clinics on the same day eliminating the need of longer plan optimization and patient-specific quality assurance. MLC-GRID provides all the dosimetry information in the planning system and potentially allow escalating dose to the bulky masses. It may allow for debulking of unresectable large tumors-opening an avenue for a neoadjuvant treatment option. Clinical follow up of these patients is ongoing.

The use of Internet-enabled technology (information and communication technology such as smartphone applications) may enrich information exchange among providers and, consequently, improve health care delivery. The purpose of this systematic review was to gain a greater understanding of the role that Internet-enabled technology plays in enhancing communication among physicians. Studies were identified through a search in three electronic platforms: the Association for Computing Machinery Digital Library, ProQuest, and Web of Science. The search identified 5140 articles; of these, 21 met all inclusion criteria. In general, physicians were satisfied with Internet-enabled technology, but consensus was lacking regarding whether Internet-enabled technology improved efficiency or made a difference to clinical decision-making. Internet-enabled technology can play an important role in enhancing communication among physicians, but the extent of that benefit is influenced by (1) the impact of Internet-enabled technology on existing work practices, (2) the availability of adequate resources, and (3) the nature of institutional elements, such as privacy legislation.

Objectives Information and communication technology is often lauded as the key to enhancing communication among health care providers. However, its impact on interprofessional collaboration is unclear. The objective of this study was to determine the extent to which it improves communication and, subsequently, enhances interprofessional collaboration in chronic disease management. Methods A systematic review of academic literature using two electronic platforms: HealthSTAR and Web of Science (core collection and MEDLINE). To be eligible for inclusion in the review, articles needed to be peer-reviewed; accessible in English and focused on how technology supports, or might support, collaboration (through enhanced communication) in chronic disease management. Studies were assessed for quality and a narrative synthesis conducted. Results The searches identified 289 articles of which six were included in the final analysis (three used qualitative methods, two were descriptive and one used mixed methods). Various forms of information and communication technology were described including electronic health records, online communities/learning resources and telehealth/telecare. Three themes emerged from the studies that may provide insights into how communication that facilitates collaboration in chronic disease management might be enhanced: professional conflict, collective engagement and continuous learning. Conclusions The success of technology in enhancing collaboration for chronic disease management depends upon supporting the social relationships and organization in which the technology will be placed. Decision-makers should take into account and work toward balancing the impact of technology together with the professional and cultural characteristics of health care teams.

Background: The use of information and communication technology (ICT) has tremendous potential to enhance communication among physicians, leading to improvements in service delivery. However, the protection of health information in digital/electronic format is an ongoing concern. Objective: The purpose of this study was to examine guidance for the protection of health information when using ICT from all 10 of Canada’s provincial regulatory colleges for physicians and to discuss the potential policy and service delivery implications. Method: A search of the regulatory college websites was conducted, followed by a document analysis (content and thematic). Results: The college website search identified 522 documents; 12 of these documents (from 8 of the 10 colleges) met the study criteria. These documents were notable for the considerable variation in the scope and detail of guidance provided across the colleges. Conclusion: While the federal–provincial division of powers in Canada enables different jurisdictional approaches to health service delivery and, thus, opportunities for policy learning, this governing structure may also contribute to a lack of incentive for collaboration, leading to an absence of standardised guidance for health information protection when using ICT. This, in turn, may result in unequal and inequitable protection of health information across the provinces. Therefore, a macro-level approach to policy development in this area may hold the greatest promise for enhancing the protection of health information and doing so in a more standardised manner in countries with federal systems of governance.

The GLO instrument concept is a VNIR/MWIR solar occultation sensor designed to measure (all at < 1 km vertical resolution) O3, H2O, CH4, CO, HF, HCN, HCl, HDO, N2O, CO2 (for temperature), and aerosol from orbital altitudes. The vertical measurement range spans the entire middle atmosphere, but the sensor has been designed to particularly target transport and composition in the UTLS. With its small form factor and modest spacecraft requirements, GLO is well suited for constellation applications. We will describe one such implementation of GLO. The instrument concept, measurement and data acquisition approach, and potential applications will be discussed.

For over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors.

Purpose Optimal curative intent brachytherapy for certain gynecologic cancers requires interstitial brachytherapy, often using template-guided techniques such as a Syed–Neblett implant. Whether high or low dose rate (LDR), these procedures pose significant risks to patients, partly attributable to the prolonged period of bed rest. Published results of free-handed permanent interstitial brachytherapy (PIB) with 131Cs demonstrate it to be an effective modality for the management of small volume gynecologic cancers. This report is the first to describe a permanent template-guided interstitial technique using 131Cs for gynecologic cancers, performed as an LDR outpatient procedure. Methods and Materials Five sequential patients with recurrent or primary gynecologic malignancies underwent template-guided PIB using 131Cs. A posttreatment planning CT was obtained immediately after the procedure and again 3–4 weeks later. Both CT data sets were fused and the relative positions compared to assess for migration in the x, y, and z planes. Seed positions as well as dosimetric parameters including D90, D100, V100, and the dose to 2 cc of rectum and bladder were compared to quantify migration of sources and the resulting effect, if any, on the treatment. Results The median age was 69 years (range 64–85). All patients received a template-guided 131Cs PIB implant to treat gross disease. All 5 patients had significant medical comorbidities that limited treatment options. Considering all 5 patients, a total of 40 interstitial needles were placed. Ten needles carried only Vicryl-stranded sources, and 30 needles carried a combination of stranded 131Cs seeds and free seeds. Needle count was between 6 and 10 needles per patient, with active lengths of 4–10 cm. The median dose was 30 Gy (range 25–55 Gy) to permanent decay, enabling a cumulative median biological effective dose 91.5 Gy (range 60.9–92.1 Gy) and equivalent dose at 2 Gy per fraction 75.9 Gy (range 50.7–76.8 Gy). All implants were performed as outpatient procedures with only the first patient admitted for 23-hour observation. All calculated median migration distances were less than 1 cm in the axial, sagittal, or coronal planes. In 69.2% cases, the individual seed migration was Conclusions Permanent LDR template-guided PIB using 131Cs can be safely performed on an outpatient basis. Compared to currently used template-guided techniques, the use of 131Cs avoids prolonged bed rest and hospitalization, significantly lowers cost, and enables a higher cumulative dose. Seed migration is minimal with this technique. Early experience suggests that the technique is safe and merits further study.

Optimizing the transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) is a priority for healthcare systems. The purpose of this systematic review is to: (1) identify and compare models of care that may be used to facilitate the transition from CAMHS to AMHS; and (2) discuss trends and implications to inform future research and practice. Results identified three models of care which move beyond healthcare services and incorporate a broader range of services that better meet the dynamic needs of transition-aged youth. Joint working among providers, coupled with individualized approaches, is essential to facilitating continuity of care.

A major cause of mortality in epilepsy patients is sudden unexpected death in epilepsy (SUDEP). Post-ictal respiratory dysfunction following generalized convulsive seizures is most commonly observed in witnessed cases of human SUDEP. DBA mouse models of SUDEP are induced by audiogenic seizures (AGSz) and show high incidences of seizure-induced death due to respiratory depression. The relatively low incidence of human SUDEP suggests that it may be useful to examine seizure-associated death in an AGSz model that rarely exhibits sudden death, such as genetically epilepsy-prone rats (GEPR-9s). Adenosine is released extensively during seizures and depresses respiration, which may contribute to seizure-induced death. The present study examined the effects of inhibiting adenosine metabolism on the durations of post-ictal depression (PID) and respiratory distress (RD), changes in blood oxygen saturation (% SpO2), and the incidence of post-seizure mortality in GEPR-9s. Systemic administration of adenosine metabolism inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 30 mg/kg) with 5-Iodotubericidin (5-ITU, 3mg/kg) in GEPR-9s resulted in significant changes in the duration of AGSz-induced PID as compared to vehicle in both genders. These agents also significantly increased the duration of post-seizure RD and significantly decreased the mean% SpO2 after AGSz, as compared to vehicle but only in females. Subsequently, we observed that the incidences of death in both genders 12-48 h post-seizure were significantly greater in drug vs. vehicle treatment. The incidence of death in females was also significantly higher than in males, which is consistent with the elevated seizure sensitivity of female GEPR-9s developmentally. These results support a potentially important role of elevated adenosine levels following generalized seizures in the increased incidence of death in GEPR-9s induced by adenosine metabolism inhibitors. These findings may also be relevant to human SUDEP, in light of the elevated adenosine levels that occur post-ictally in humans and its respiratory depressant actions.

Background Youth with mental health disorders often experience challenges when transitioning into adult roles (e.g. independent living, work and community engagement). Health interventions that address the needs of youth with mental health disorders during these challenges in their development (i.e. developmental transitions) have not been reviewed in the literature. This scoping review examines the peer-reviewed research that describes evaluated interventions addressing developmental transitions for youth with mental health disorders. Methods A search of four prominent health literature databases (CINAHL, Embase, MEDLINE and PsycINFO) was conducted to identify evaluated developmental transition interventions for adolescents and youth (12–25 years) with mental health disorders. Study selection and analysis were guided by a methodological framework for conducting scoping reviews. Selected studies were described, assessed for quality and collated based on ten dimensions from two notable conceptual frameworks in developmental transitions and disability. Results Nine studies met the inclusion criteria. The interventions within these studies demonstrated five specialized and four multi-faceted programmes (i.e. multiple domains). All domains from the two conceptual frameworks were represented differently across studies. The sub-domains from these studies were most frequently related to vocational-focused interventions, least frequently related to social activities and living situation and did not explicitly map onto the sexuality sub-domain. Three multi-faceted interventions incorporated all domains and utilized each intervention approach. Study quality was rated for seven of the nine studies. Quantitative methodology for five of the seven studies was rated as higher quality. Conclusions Evaluated interventions described in the transitions literature for youth with mental health disorders predominantly focus on vocational needs. The least studied areas were the personal and interpersonal domains. These domains were only incorporated within interventions addressing multiple domains of developmental transitions. These insights can be helpful in guiding evidence-based practice and policy development, as well as informing gaps for future research programmes.

The health needs of the lesbian, gay, bisexual, and transgender (LGBT) population are traditionally overlooked by the health care community and are rendered invisible by most nursing school curricula. Initial contact with a nurse during a health history and assessment can have an impact on whether the person will feel comfortable disclosing his or her identity, returning for services, or following plans of care. Because the first interaction with a nurse can be critical, the health assessment course is an appropriate place in the curriculum to discuss the needs of the LGBT community. This article includes a discussion of unique health risks to the LGBT population, benefits, and challenges of incorporating these issues into the classroom and recommendations for including the care of this population into a health assessment nursing course. Specific communication techniques are provided that may be helpful during history taking and physical examination with a patient who is LGBT. Guidance regarding physical examination of the transgender patient is also included. These suggestions will be helpful to nurse faculty who teach health assessment, nursing students, educators who design and implement professional development and continuing education for established nurses, preceptors in the clinical setting, and any nurse who is unfamiliar with the needs and concerns specific to the LGBT population.

Youth shifting to adult mental health services often report experiencing frustrations with accessing care that adequately replaces the youth services they had received. This systematic review assesses the peer reviewed evidence on services/programs aimed at addressing youth to adult transitions in mental health services. Findings suggest little data exists on the effectiveness of transition services/programs. While the available evidence supports meetings between youth and youth caseworkers prior to transitions occurring, it also verifies that this is not common practice. Other identified barriers to effective transitions were categorized as logistical (ineffective system communication), organizational (negative incentives), and related to clinical governance.

As the ease of obtaining genetic information for both the diagnosis and treatment of diseases has become increasingly common, so have concerns about the misuse of such information. The obstacles Canada faces in adopting genetic non-discrimination legislation have left health leaders with a lack of clear direction. Using the Kingdon agenda-setting framework, this article will identify lost opportunities for policy change and will analyze the potential for the adoption of a genetic non-discrimination policy in Canada. Windows of opportunity for policy change have existed in the past, but these windows have closed prior to a policy being adopted. More recently, the alignment of problem, policy, and politics streams in the agenda-setting process has resulted in a new window of opportunity. The adoption of a clear and coherent policy will provide the public with protection and health leaders with greater direction around genetic information.

Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered a first response to a smallpox emergency in subjects of uncertain exposure status or as a means of reduction of the incidence and severity of vaccine-associated adverse events.

In the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP), administration of a selective serotonin (5-HT) reuptake inhibitor (SSRI), fluvoxamine, completely suppressed seizure-induced respiratory arrest (S-IRA) at 30 min after administration (i.p.) in a dose-related manner without blocking audiogenic seizures (AGSz), but another SSRI, paroxetine, reduced S-IRA but with a delayed (24 h) onset and significant toxicity. A serotonin–norepinephrine reuptake inhibitor, venlafaxine, reduced S-IRA incidence, but higher doses were ineffective. A selective 5-HT7 agonist, AS-19, was totally ineffective in reducing S-IRA. In developing DBA/1 mice that had not previously experienced AGSz, administration of a nonselective 5-HT antagonist, cyproheptadine, induced a significantly greater incidence of S-IRA than that of saline. This study confirms that certain drugs that enhance the activation of 5-HT receptors are able to prevent S-IRA, but not all serotonergic drugs are equally effective, which may be relevant to the potential use of these drugs for SUDEP prevention. Serotonergic antagonists may be problematic in patients with epilepsy.

Despite a dramatic growth in SDH/HE (social determinants of health/health equity) public policy research and demonstrated government interest in promoting equity in health policies, health inequities are actually growing among some populations and there is little evidence that "healthy public policies" are being adopted and implemented. Moreover, these issues are typically failing to even reach governments' policy agendas, which is a critical step towards serious debate and the identification of policy options. This systematic review pursues three main objectives. First, is to identify barriers to SDH/HE issues reaching the government policy agenda. Second, to evaluate the characteristics of peer-reviewed research articles that utilize common policy analysis theories. And third, to determine the extent to which the SDH/HE literature utilizes common policy analysis theories. Our systematic review, conducted in June 2012, identified 6200 SDH/HE related articles in the peer-reviewed literature; however, only seven articles explicitly used a commonly recognized policy analysis theory to inform their analysis. Our analysis revealed that the SDH/HE policy literature appears to be focused on advocacy rather than analysis and that the use of policy analysis theory is extremely limited. Our results also suggest that when such theories are incorporated into an analysis they are often not comprehensively employed. We propose explanations for this non-use and misuse of policy analysis theory, and conclude that researchers may have greater influence in helping to get SDH/HE issues onto government policy agendas if they gain a greater understanding of the policy process and the value of incorporating policy analysis theories into their research. Using a policy analysis lens to help identify why healthy public policies are typically not being adopted is an important step towards moving beyond advocacy to understanding and addressing some of the political barriers to reforms.

The Cloud Imaging and Particle Size (CIPS) instrument has been in operation on the NASA Aeronomy of Ice in the Mesosphere (AIM) satellite since May 2007. CIPS is a multi-camera UV imager that makes unprecedented hemispheric-scale measurements of polar mesospheric clouds (PMC). The primary CIPS data products are cloud frequency, albedo, mean particle radius, ice water content and vertical column particle density. These quantities are retrieved at 25 km2 resolution at latitudes between ~55° and 84° over a range of local times in the summer hemisphere. CIPS has obtained data for six Northern Hemisphere and five Southern Hemisphere PMC seasons to date and is still in operation and performing flawlessly. The CIPS data are made available to the scientific community in a variety of formats and spatial and temporal resolution, including full-resolution single-orbit level 2 data files and images, daily (hemispheric) albedo maps and images, and full-season latitude-binned summary files. In this paper we describe the CIPS measurement strategy and sampling characteristics, calibration and the Version 4.20 processing algorithms and retrievals. We also provide a quantitative evaluation of the CIPS cloud detection sensitivity and estimated random and systematic errors of the V4.20 cloud data products.

Objectives Factors influencing xerostomia during intensity-modulated radiation therapy (IMRT) were assessed. Methods A 6-week study of 32 head and neck cancer (HNC) patients was performed. Subjects completed the Xerostomia Inventory (XI) and provided stimulated saliva (SS) at baseline, week 2 and at end of IMRT. Influence of SS flow rate (SSFR), calcium and mucin 5b (MUC5b) concentrations and radiation dose on xerostomia was determined. Results HNC subjects experienced mean SSFR decline of 36% by visit 2 ( N = 27; P = .012) and 57% by visit 3 ( N = 20; P = .0004). Concentrations of calcium and MUC5b increased, but not significantly during IMRT ( P > .05). Xerostomia correlated most with decreasing salivary flow rate as determined by Spearman correlations ( P P Conclusions Although IMRT is sparing to the parotid glands, it has an early effect on SSFR and the constituents in saliva in a manner that is associated with the perception of xerostomia.

Purpose To present a time-to-failure (TTF) analysis for all patients treated with permanent interstitial brachytherapy (PIB) at our institution, with additional analyses to correlate successful reirradiation and to identify the frequency of severe grade 3 to 4 toxicity. Methods and Materials Forty-two previously irradiated patients received curative or palliative intent PIB for a recurrent pelvic malignancy between January 2009 and August 2016. Minimum follow-up was 6 months after the PIB procedure. All patients had a biopsy-proven recurrence and were treated using PIB alone (n=32) or in combination with a short course of additional radiation therapy (n=10). Competing risk analyses were performed to assess the risk of failures in the presence of death without failure. Exploratory analyses were performed for factors related to failure using competing risk analyses and the Gray statistic. Results A total of 61 PIB implants were performed among 42 patients with a median follow-up of 16.3 months. Fifty-two implants were performed as the first salvage reirradiation to a solitary recurrence (8 patients had more than 1 lesion); the success rate for initial reirradiation using PIB was 73% (38 cases out of 52), and the median TTF was not reached. Nine patients underwent a second repeat PIB to the same recurrence as a form of salvage; 3 (33%) remain without evidence of recurrence. The median TTF after second salvage was 7.7 months. Even with the limited sample size, prolonged TTF was marginally associated with definitive intent (P=.07) and the extent of disease at the time of PIB (P=.08). Grade 3+ toxicities were seen in 8 patients (16.7%). Conclusions Permanent interstitial brachytherapy is a feasible and potentially durable treatment modality that can be used to curatively salvage selected recurrent pelvic malignancies in a previously irradiated field.

Background Inequality between most Canadians and those from Inuit and First Nations communities, in terms of both access to oral health care services and related health outcomes, has been a long-standing problem. Efforts to close this equity gap led to the creation of dental therapy training programs. These programs were designed to produce graduates who would provide services in rural and northern communities. The closure of the last dental therapy program in late 2011 has ended the supply of dental therapists and governments do not appear to have any alternative solutions to the growing gap in access to oral health care services between most Canadians and those from Inuit and First Nations communities. Methods A policy analysis of the rise and fall of the dental therapy profession in Canada was conducted using historical and policy documents. The analysis is framed within Kingdon’s agenda-setting framework and considers why dental therapy was originally pursued as an option to ensure equitable access to oral health care for Inuit and First Nations communities and why this policy has now been abandoned with the closure of Canada’s last dental therapy training school. Results The closure of the last dental therapy program in Canada has the potential to further reduce access to dental care in some Inuit and First Nations communities. Overlaps between federal and provincial jurisdiction have contributed to the absence of a coordinated policy approach to address the equity gap in access to dental care which will exacerbate the inequalities in comparison to the general population. The analysis suggests that while a technically feasible policy solution is available there continues to be no politically acceptable solution and thus it remains unlikely that a window of opportunity for policy change will open any time soon. Conclusion In the absence of federal government leadership, the most viable option forward may be incremental policy change. Provincial governments could expand the scope of practice for dental hygienists in the hope that it may support enhanced access, consumer choice, and efficiency in the delivery of oral health care to Inuit and First Nations communities in Canada.