Feasibility, acceptability and clinical benefit of a trauma-focused stabilisation group for post-traumatic stress disorder patients with complex presentations on primary care waitlists.

BACKGROUND: Large numbers of people showing complex presentations of post-traumatic stress disorder (PTSD) in the NHS Talking Therapies services routinely require multi-faceted and extended one-to-one National Institute of Clinical Excellence (NICE) recommended treatment approaches. This can lead to longer waits for therapy and prolong patient suffering. We therefore evaluated whether a group stabilisation intervention delivered to patients on the waitlist for individual trauma-focused psychological treatment could help address this burden. AIMS: The study aimed to ascertain a trauma-focused stabilisation group's acceptability, feasibility, and preliminary clinical benefit. METHOD AND RESULTS: Fifty-eight patients with PTSD waiting for trauma-focused individual treatment were included in the study. Two therapists delivered six 5-session groups. The stabilisation group was found to be feasible and acceptable. Overall, PTSD symptom reduction was medium to large, with a Cohen's d of .77 for intent-to-treat and 1.05 for per protocol analyses. Additionally, for depression and anxiety, there was minimal symptom deterioration. CONCLUSIONS: The study provided preliminary evidence for the acceptability, feasibility and clinical benefit of attending a psychoeducational group therapy whilst waiting for one-to-one trauma therapy.

Transvection between nonallelic genomic positions in Drosophila.

In Drosophila, pairing of maternal and paternal homologous chromosomes can permit trans-interactions between enhancers on one homolog and promoters on another, an example of transvection. Although trans-interactions have been observed at many loci in the Drosophila genome and in other organisms, the parameters that govern enhancer action in trans remain poorly understood. Using a transgenic reporter system, we asked whether enhancers and promoters at nonallelic, but nearby, genomic positions can communication in trans. Using one transgenic insertion carrying the synthetic enhancer GMR and another nearby insertion carrying the hsp70 promoter driving a fluorescent reporter, we show that transgenes separated by 2.6 kb of linear distance can support enhancer action in trans at the 53F8 locus. Furthermore, transvection between the nonallelic insertions can be augmented by a small deletion flanking one insert, likely via changes to the paired configuration of the homologs. Subsequent analyses of other insertions in 53F8 that carry different transgenic sequences demonstrate that the capacity to support transvection between nonallelic sites varies greatly, suggesting that factors beyond the linear distance between insertion sites play an important role. Finally, analysis of transvection between nearby nonallelic sites at other genomic locations shows evidence of position effects, where one locus supported GMR action in trans over a linear distance of over 10 kb, whereas another locus showed no evidence of transvection over a span <200 bp. Overall, our data demonstrate that transvection between nonallelic sites represents a complex interplay between genomic context, interallelic distance, and promoter identity.

Medical Physics Leadership Academy Journal Club (Leadership Club) program: Two-year review in building a community of leaders.

The American Association of Physicists in Medicine began the Medical Physics Leadership Academy Journal Club in the fall of 2020. The initiative was launched to provide a forum for medical physicists to learn about leadership topics using published material, discuss and reflect on the material, and consider incorporating the discussed skills into their professional practice. This report presents the framework for the MPLA Journal Club program, describes the lessons learned over the last 2 years, summarizes the data collected from attendees, and highlights the roadmap for the program moving forward.

AAPM task group report 275.S: Survey strategy and results on plan review and chart check practices in US and Canada.

BACKGROUND: AAPM Task Group (TG) 275 was charged with developing practical, evidence-based recommendations for physics plan and chart review clinical processes for radiation therapy. As part of this charge, and to characterize practices and clinical processes, a survey of the medical physics community was developed and conducted. Detailed analyses and trends based on the survey that exceeded TG report length constraints are presented herein. AIMS: The design, development, and detailed results of the TG- 275 survey as well as statistical analysis and trends are described in detail. This is complementary material to the TG 275 report. METHODS AND MATERIALS: The survey consisted of 100 multiple-choice questions divided into four main sections: 1) Demographics, 2) Initial Plan Check, 3) On-Treatment, and 4) End-of-Treatment Chart Check. The survey was released to all AAPM members who self-reported working in the radiation oncology field, and it was kept open for 7 weeks. Results were summarized using descriptive statistics. To study practice differences, tests of association were performed using data grouped by four demographic questions: 1) Institution Type, 2) Average number of patients treated daily, 3) Radiation Oncology Electronic Medical Record, and 4) Perceived Culture of Safety. RESULTS: The survey captured 1370 non-duplicate entries from the United States and Canada. Differences across practices were grouped and presented based on Process-Based and Check-Specific questions. A risk-based summary was created to show differences amongst the four demographic questions for checks associated with the highest risk failure modes identified by TG-275. CONCLUSION: The TG-275 survey captured a baseline of practices on initial plan, on-treatment, and end-of-treatment checks across a wide variety of clinics and institutions. The results of test of association showed practice heterogeneities as a function of demographic characteristics. Survey data were successfully used to inform TG-275 recommendations.

Development and multi-institutional validation of a convolutional neural network to detect vertebral body mis-alignments in 2D x-ray setup images.

BACKGROUND: Misalignment to the incorrect vertebral body remains a rare but serious patient safety risk in image-guided radiotherapy (IGRT). PURPOSE: Our group has proposed that an automated image-review algorithm be inserted into the IGRT process as an interlock to detect off-by-one vertebral body errors. This study presents the development and multi-institutional validation of a convolutional neural network (CNN)-based approach for such an algorithm using patient image data from a planar stereoscopic x-ray IGRT system. METHODS: X-rays and digitally reconstructed radiographs (DRRs) were collected from 429 spine radiotherapy patients (1592 treatment fractions) treated at six institutions using a stereoscopic x-ray image guidance system. Clinically-applied, physician approved, alignments were used for true-negative, "no-error" cases. "Off-by-one vertebral body" errors were simulated by translating DRRs along the spinal column using a semi-automated method. A leave-one-institution-out approach was used to estimate model accuracy on data from unseen institutions as follows: All of the images from five of the institutions were used to train a CNN model from scratch using a fixed network architecture and hyper-parameters. The size of this training set ranged from 5700 to 9372 images, depending on exactly which five institutions were contributing data. The training set was randomized and split using a 75/25 split into the final training/ validation sets. X-ray/ DRR image pairs and the associated binary labels of "no-error" or "shift" were used as the model input. Model accuracy was evaluated using images from the sixth institution, which were left out of the training phase entirely. This test set ranged from 180 to 3852 images, again depending on which institution had been left out of the training phase. The trained model was used to classify the images from the test set as either "no-error" or "shifted", and the model predictions were compared to the ground truth labels to assess the model accuracy. This process was repeated until each institution's images had been used as the testing dataset. RESULTS: When the six models were used to classify unseen image pairs from the institution left out during training, the resulting receiver operating characteristic area under the curve values ranged from 0.976 to 0.998. With the specificity fixed at 99%, the corresponding sensitivities ranged from 61.9% to 99.2% (mean: 77.6%). With the specificity fixed at 95%, sensitivities ranged from 85.5% to 99.8% (mean: 92.9%). CONCLUSION: This study demonstrated the CNN-based vertebral body misalignment model is robust when applied to previously unseen test data from an outside institution, indicating that this proposed additional safeguard against misalignment is feasible.

Medical Physics Practice Guideline (MPPG) 11.a: Plan and chart review in external beam radiotherapy and brachytherapy.

A therapeutic medical physicist is responsible for reviewing radiation therapy treatment plans and patient charts, including initial treatment plans and new chart review, on treatment chart (weekly) review, and end of treatment chart review for both external beam radiation and brachytherapy. Task group report TG 275 examined this topic using a risk-based approach to provide a thorough analysis and guidance for best practice. Considering differences in resources and workflows of various clinical practice settings, the Professional Council of the American Association of Physicists in Medicine assembled this task group to develop a practice guideline on the same topic to provide a minimum standard that balances an appropriate level of safety and resource utilization. This medical physics practice guidelines (MPPG) thus provides a concise set of recommendations for medical physicists and other clinical staff regarding the review of treatment plans and patient charts while providing specific recommendations about who to be involved, and when/what to check in the chart review process. The recommendations, particularly those related to the initial plan review process, are critical for preventing errors and ensuring smooth clinical workflow. We believe that an effective review process for high-risk items should include multiple layers with collective efforts across the department. Therefore, in this report, we make specific recommendations for various roles beyond medical physicists. The recommendations of this MPPG have been reviewed and endorsed by the American Society of Radiologic Technologists and the American Association of Medical Dosimetrists.

Fully Balanced SSFP Without an Endorectal Coil for Postimplant QA of MRI-Assisted Radiosurgery (MARS) of Prostate Cancer: A Prospective Study.

PURPOSE: To investigate fully balanced steady-state free precession (bSSFP) with optimized acquisition protocols for magnetic resonance imaging (MRI)-based postimplant quality assessment of low-dose-rate (LDR) prostate brachytherapy without an endorectal coil (ERC). METHODS AND MATERIALS: Seventeen patients at a major academic cancer center who underwent MRI-assisted radiosurgery (MARS) LDR prostate cancer brachytherapy were imaged with moderate, high, or very high spatial resolution fully bSSFP MRIs without using an ERC. Between 1 and 3 signal averages (NEX) were acquired with acceleration factors (R) between 1 and 2, with the goal of keeping scan times between 4 and 6 minutes. Acquisitions with R >1 were reconstructed with parallel imaging and compressed sensing (PICS) algorithms. Radioactive seeds were identified by 3 medical dosimetrists. Additionally, some of the MRI techniques were implemented and tested at a community hospital; 3 patients underwent MARS LDR prostate brachytherapy and were imaged without an ERC. RESULTS: Increasing the in-plane spatial resolution mitigated partial volume artifacts and improved overall seed and seed marker visualization at the expense of reduced signal-to-noise ratio (SNR). The reduced SNR as a result of imaging at higher spatial resolution and without an ERC was partially compensated for by the multi-NEX acquisitions enabled by PICS. Resultant image quality was superior to the current clinical standard. All 3 dosimetrists achieved near-perfect precision and recall for seed identification in the 17 patients. The 3 postimplant MRIs acquired at the community hospital were sufficient to identify 208 out of 211 seeds implanted without reference to computed tomography (CT). CONCLUSIONS: Acquiring postimplant prostate brachytherapy MRI without an ERC has several advantages including better patient tolerance, lower costs, higher clinical throughput, and widespread access to precision LDR prostate brachytherapy. This prospective study confirms that the use of an ERC can be circumvented with fully bSSFP and advanced MRI scan techniques in a major academic cancer center and community hospital, potentially enabling postimplant assessment of MARS LDR prostate brachytherapy without CT.

Strategies for effective physics plan and chart review in radiation therapy: Report of AAPM Task Group 275.

BACKGROUND: While the review of radiotherapy treatment plans and charts by a medical physicist is a key component of safe, high-quality care, very few specific recommendations currently exist for this task. AIMS: The goal of TG-275 is to provide practical, evidence-based recommendations on physics plan and chart review for radiation therapy. While this report is aimed mainly at medical physicists, others may benefit including dosimetrists, radiation therapists, physicians and other professionals interested in quality management. METHODS: The scope of the report includes photon/electron external beam radiotherapy (EBRT), proton radiotherapy, as well as high-dose rate (HDR) brachytherapy for gynecological applications (currently the highest volume brachytherapy service in most practices). The following review time points are considered: initial review prior to treatment, weekly review, and end-of-treatment review. The Task Group takes a risk-informed approach to developing recommendations. A failure mode and effects analysis was performed to determine the highest-risk aspects of each process. In the case of photon/electron EBRT, a survey of all American Association of Physicists in Medicine (AAPM) members was also conducted to determine current practices. A draft of this report was provided to the full AAPM membership for comment through a 3-week open-comment period, and the report was revised in response to these comments. RESULTS: The highest-risk failure modes included 112 failure modes in photon/electron EBRT initial review, 55 in weekly and end-of-treatment review, 24 for initial review specific to proton therapy, and 48 in HDR brachytherapy. A 103-question survey on current practices was released to all AAPM members who self-reported as working in the radiation oncology field. The response rate was 33%. The survey data and risk data were used to inform recommendations. DISCUSSION: Tables of recommended checks are presented and recommendations for best practice are discussed. Suggestions to software vendors are also provided. CONCLUSIONS: TG-275 provides specific recommendations for physics plan and chart review which should enhance the safety and quality of care for patients receiving radiation treatments.

Intrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The ISPR was initially created to monitor the product performance of Medtronic implanted intrathecal drug infusion and spinal cord systems available in the United States. MATERIALS AND METHODS: Data were collected from 50 representative sites implanting and following patients with intrathecal drug delivery systems across the United States between August 7, 2003 and January 31, 2014. Device performance over time was estimated using life table survival methods. RESULTS: Of the 6093 patients enrolled in the ISPR, 3405 (55.9%) were female and 2675 (43.9%) were male, and 13 (0.2%) did not provide gender data. The average age at enrollment was 52.9 years (SD =17.6 years) and average follow-up time was 29.6 months. Currently, the estimates of device survival from pump-related events exceed 90% for all pump models across the applicable follow-up time points. The majority of product performance events were catheter-related. At 5 years of follow-up, all applicable catheter models, with the exception of revised not as designed or grafted not as designed catheters, had greater than 81% survival from catheter-related events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Spinal Cord Stimulation (SCS)-The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States. MATERIALS AND METHODS: Data were collected on 2605 patients from 44 centers from various geographic regions across the United States implanting and following patients with SCS systems between June 25, 2004 and January 31, 2014. Actuarial life table methods are used to estimate device performance over time. Of the 2605 patients, 1490 (57.2%) were female, 1098 (42.1%) were male and 17 (0.7%) did not provide gender data. The average age at enrollment was 56.3 years (range: 4-97, SD = 14.3) and average follow-up time was 20.1 months (SD = 22.5). RESULTS: Currently the estimates of device survival from neurostimulator-related events exceed 97% for all neurostimulator models across the applicable follow-up time points and all applicable extension models had greater than 95% survival from extension events. The majority of product performance events were lead-related. At 5 years of follow-up, all applicable lead families, with the exception of the Pisces-Quad LZ family, had greater than 75% survival from lead events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Phosphatidylinositol 3-kinase and Akt nonautonomously promote perineurial glial growth in Drosophila peripheral nerves.

Drosophila peripheral nerves, structured similarly to their mammalian counterparts, comprise a layer of motor and sensory axons wrapped by an inner peripheral glia (analogous to the mammalian Schwann cell) and an outer perineurial glia (analogous to the mammalian perineurium). Growth and proliferation within mammalian peripheral nerves are increased by Ras pathway activation: loss-of-function mutations in Nf1, which encodes the Ras inhibitor neurofibromin, cause the human genetic disorder neurofibromatosis, which is characterized by formation of neurofibromas (tumors of peripheral nerves). However, the signaling pathways that control nerve growth downstream of Ras remain incompletely characterized. Here we show that expression specifically within the Drosophila peripheral glia of the constitutively active Ras(V12) increases perineurial glial thickness. Using chromosomal loss-of-function mutations and transgenes encoding dominant-negative and constitutively active proteins, we show that this nonautonomous effect of Ras(V12) is mediated by the Ras effector phosphatidylinositol 3-kinase (PI3K) and its downstream kinase Akt. We also show that the nonautonomous, growth-promoting effects of activated PI3K are suppressed by coexpression within the peripheral glia of FOXO+ (forkhead box O) a transcription factor inhibited by Akt-dependent phosphorylation. We suggest that Ras-PI3K-Akt activity in the peripheral glia promotes growth of the perineurial glia by inhibiting FOXO. In mammalian peripheral nerves, the Schwann cell releases several growth factors that affect the proliferative properties of neighbors. Some of these factors are oversecreted in Nf1 mutants. Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a Ras-PI3K-Akt-dependent inhibition of FOXO within Schwann cells.

Pepsinogen C expression in intestinal IEC-6 cells.

Pepsinogen C (PGC) is the inactive precursor of pepsin C, which is a member of the aspartic proteinase family of proteolytic enzymes, and is found within the vertebrate stomach. The precursor molecule is synthesised within the gastric epithelial cells and secreted into the gastric lumen where it undergoes an autocatalytic activation under acidic conditions to the proteolytic molecule. However, the synthesis of PGC has also been reported in numerous non-gastric tissues including the prostate gland and the Brunner's gland of the small intestine. The physiological significance of PGC in these tissues is not known and studies are limited by the lack of appropriate in vitro cell models. We report here the use of the rat intestinal cell line, IEC-6, as an in vitro model to study the role of pepsinogen C in the intestine. PGC expression was detected in the IEC-6 cells by RT-PCR and immunocytochemistry, using a PGC specific antibody, localised the protein to cytoplasmic secretory granules. Enzymatic assay confirmed the presence of a functional protein exhibiting pepsin activity. Using semi-quantitative RT-PCR we showed that PGC gene expression was up-regulated by the gastro-intestinal hormones gastrin and secretin, and forskolin which stimulates adenylate cyclase activity. This study demonstrates that the IEC-6 cells provide a unique in vitro model for studying pepsinogen C and its potential role(s) in the small intestine.

Oxygen debt criteria quantify the effectiveness of early partial resuscitation after hypovolemic hemorrhagic shock.

BACKGROUND: The effectiveness of partial resuscitation after hypovolemic hemorrhagic shock with deferment of full resuscitation is critical to successful hypotensive resuscitation. METHODS: To quantitatively address this issue, 40 canines were bled under anesthesia to a mean oxygen debt (O(2)D) of 104 +/- 7.6 mL/kg over 60 minutes (mortality, 40%). Animals surviving the shock were then immediately resuscitated with 0%, 8.4%, 15%, 30%, or 120% (full resuscitation) of shed volume as 5% albumin and held for 2 hours postshock, when the remaining portion of full resuscitation volume was given. Animals were followed for 7 days postshock with hepatic and renal function studies, and then, under anesthesia, cardiac output and organ biopsy specimens were taken before the animals were killed. RESULTS: By 2 hours postshock, 0% immediate resuscitation had an O(2)D increase of 80 mL/kg above end of shock, but O(2)D at 8.4% immediate resuscitation decreased -30 mL/kg, 15% immediate resuscitation fell -65 mL/kg, 30% immediate resuscitation decreased -80 mL/kg below end of shock, and O(2)D with 120% full resuscitation fell to preshock levels. All decreases in O(2)D were significantly (p < 0.05) below end of shock, but both 15% and 30% immediate resuscitation exceeded the 8.4% immediate resuscitation rate (p < 0.05) throughout the resuscitation, and 120% full resuscitation exceeded these (p < 0.05). The immediate resuscitation O(2)D response correlated significantly (p < 0.001) with base deficit and lactate, but blood pressure was not a significant discriminator. Seven-day biopsies showed return of bowel mucosa but a pattern of cellular injury in heart, liver, and kidney that improved from 8.4% < 15% < 30 < 120% immediate resuscitation. CONCLUSION: The data suggest that, compared with 120% postshock immediate resuscitation, 8.4% and 15% immediate resuscitation give poorer results, with 30% immediate resuscitation showing mild, transient, but acceptable changes in organ function allowing for a 2-hour delay until full resuscitation, with complete 7-day recovery. Base deficit and lactate, but not blood pressure, are significant indices of O(2)D.