Requesting That Delirium Achieve Parity With Acute Encephalopathy in the MS-DRG System.

Since 2007, the Medicare Severity Diagnosis Related Groups classification system has favored billing codes for acute encephalopathy over delirium codes in determining hospital reimbursement and several quality-of-care value metrics, despite broad overlap between these sets of diagnostic codes. Toxic and metabolic encephalopathy codes are designated as major complication or comorbidity, whereas causally specified delirium codes are designated as complication or comorbidity and thus associated with a lower reimbursement and lesser impact on value metrics. The authors led a submission to the U.S. Centers for Medicare and Medicaid Services requesting that causally specified delirium be designated major complication or comorbidity alongside toxic and metabolic encephalopathy. Delirium warrants reclassification because it satisfies U.S. Centers for Medicare and Medicaid Services' guiding principles for re-evaluating Medicare Severity Diagnosis Related Group severity levels. Delirium: (1) has a bidirectional relationship with the permanent condition of dementia (major neurocognitive disorder per DSM-5-TR), (2) indexes vulnerability across populations, (3) impacts healthcare systems across levels of care, (4) complicates postoperative recovery, (5) consigns patients to higher levels of care, (6) impedes patient engagement in care, (7) has several recent treatment guidelines, (8) often indicates neuronal/brain injury, and (9) represents a common expression of terminal illness. The proposal's impact was explored using the 2019 National Inpatient Sample, which suggested that increasing delirium's complexity designation would lead to an upcoding of less than 1% of eligible discharges. Parity for delirium is essential to enhancing awareness of delirium's clinical and economic costs. Appreciating delirium's impact would encourage delirium prevention and screening efforts, thereby mitigating its dire outcomes for patients, families, and healthcare systems.

Development and Preliminary Evaluation of a Murine Model of Chronic Radiation-Induced Proctitis.

PURPOSE: Radiotherapy (RT) is commonly used to treat most pelvic malignancies. While treatment is often effective, curative radiation doses to the rectum can result in chronic radiation-induced proctitis, which is characterized by diarrhea, tenesmus, and/or rectal bleeding, recently termed pelvic radiation disease. An animal model of chronic radiation-induced proctitis would be useful to test both preventative and therapeutic strategies to limit this morbidity but has been elusive because of the high rodent mortality associated with acute bowel RT injury. The objective of this research was to develop a novel mouse model of chronic radiation-induced proctitis using advanced technology. METHODS AND MATERIALS: Using an X-RAD 225-Cx (Precision X-Ray) small animal irradiator, multiple plan configurations were evaluated for planning treatment volume and organ-at-risk avoidance to deliver a 15 Gy 3D conformal treatment plan. The final plan was verified by high resolution 3D dosimetry (PRESAGE/optical-CT), and delivered using a single arc. Mice were monitored for mortality for 250 days, followed by histopathological correlates including mucicarmine, Masson's trichrome, and fecal pellet length. RESULTS: Six beam arrangements were considered: single and parallel-opposed fields with whole-pelvis coverage, and collimated fields in parallel-opposed, 3-field, 4-field, and arc geometries. A collimated arc plan offered superior planning treatment volume coverage and organ-at-risk avoidance compared to whole-pelvis irradiation. Treatment verification with PRESAGE 3D dosimetry (Heuris Inc) showed >99% of voxels passing gamma analysis with 2%/2 mm criteria. Our treatment resulted in no acute mortality and 40% mortality at 250 days. Histopathological analysis showed increased mucous production and fibrosis of the irradiated colon, but no change in fecal pellet length. CONCLUSIONS: Our model was able to target successfully lower colon and rectum with lower mortality than other published models. This permitted measurement of late effects that recapitulate some features of rectal damage in humans.

Technical Note: On maximizing Cherenkov emissions from medical linear accelerators.

PURPOSE: Cherenkov light during MV radiotherapy has recently found imaging and therapeutic applications but is challenged by relatively low fluence. Our purpose is to investigate the feasibility of increasing Cherenkov light production during MV radiotherapy by increasing photon energy and applying specialized beam-hardening filtration. METHODS: GAMOS 5.0.0, a GEANT4-based framework for Monte Carlo simulations, was used to model standard clinical linear accelerator primary photon beams. The photon source was incident upon a 17.8 cm3 cubic water phantom with a 94 cm source to surface distance. Dose and Cherenkov production was determined at depths of 3-9 cm. Filtration was simulated 15 cm below the photon beam source. Filter materials included aluminum, iron, and copper with thicknesses of 2-20 cm. Histories used depended on the level of attenuation from the filter, ranging from 100 million to 2 billion. Comparing average dose per history also allowed for evaluation of dose-rate reduction for different filters. RESULTS: Overall, increasing photon beam energy is more effective at improving Cherenkov production per unit dose than is filtration, with a standard 18 MV beam yielding 3.3-4.0× more photons than 6 MV. Introducing an aluminum filter into an unfiltered 2400 cGy/min 10 MV beam increases the Cherenkov production by 1.6-1.7×, while maintaining a clinical dose rate of 300 cGy/min, compared to increases of ~1.5× for iron and copper. Aluminum was also more effective than the standard flattening filter, with the increase over the unfiltered beam being 1.4-1.5× (maintaining 600 cGy/min dose rate) vs 1.3-1.4× for the standard flattening filter. Applying a 10 cm aluminum filter to a standard 18 MV, photon beam increased the Cherenkov production per unit dose to 3.9-4.3× beyond that of 6 MV (vs 3.3-4.0× for 18 MV with no aluminum filter). CONCLUSIONS: Through a combination of increasing photon energy and applying specialized beam-hardening filtration, the amount of Cherenkov photons per unit radiotherapy dose can be increased substantially.

Three-Dimensional Dosimetric Validation of a Magnetic Resonance Guided Intensity Modulated Radiation Therapy System.

PURPOSE: To validate the dosimetric accuracy of a commercially available magnetic resonance guided intensity modulated radiation therapy (MRgIMRT) system using a hybrid approach: 3-dimensional (3D) measurements and Monte Carlo calculations. METHODS AND MATERIALS: We used PRESAGE radiochromic plastic dosimeters with remote optical computed tomography readout to perform 3D high-resolution measurements, following a novel remote dosimetry protocol. We followed the intensity modulated radiation therapy commissioning recommendations of American Association of Physicists in Medicine Task Group 119, adapted to incorporate 3D data. Preliminary tests ("AP" and "3D-Bands") were delivered to 9.5-cm usable diameter cylindrical PRESAGE dosimeters to validate the treatment planning system (TPS) for nonmodulated deliveries; assess the sensitivity, uniformity, and rotational symmetry of the PRESAGE dosimeters; and test the robustness of the remote dosimetry protocol. Following this, 4 clinical MRgIMRT plans ("MultiTarget," "Prostate," "Head/Neck," and "C-Shape") were measured using 13-cm usable diameter PRESAGE dosimeters. For all plans, 3D-γ (3% or 3 mm global, 10% threshold) passing rates were calculated and 3D-γ maps were examined. Point doses were measured with an IBA-CC01 ionization chamber for validation of absolute dose. Finally, by use of an in-house-developed, GPU-accelerated Monte Carlo algorithm (gPENELOPE), we independently calculated dose for all 6 Task Group 119 plans and compared against the TPS. RESULTS: For PRESAGE measurements, 3D-γ analysis yielded passing rates of 98.7%, 99.2%, 98.5%, 98.0%, 99.2%, and 90.7% for AP, 3D-Bands, MultiTarget, Prostate, Head/Neck, and C-Shape, respectively. Ion chamber measurements were within an average of 0.5% (±1.1%) from the TPS dose. Monte Carlo calculations demonstrated good agreement with the TPS, with a mean 3D-γ passing rate of 98.5% ± 1.9% using a stricter 2%/2-mm criterion. CONCLUSIONS: We have validated the dosimetric accuracy of a commercial MRgIMRT system using high-resolution 3D techniques. We have demonstrated for the first time that hybrid 3D remote dosimetry is a comprehensive and feasible approach to commissioning MRgIMRT. This may provide better sensitivity in error detection compared with standard 2-dimensional measurements and could be used when implementing complex new magnetic resonance guided radiation therapy technologies.

Impact of Delirium After Hip Fracture Surgery on One-Year Mortality in Patients With or Without Dementia: A Case of Effect Modification.

OBJECTIVES: We evaluated whether delirium after hip fracture repair modifies the relationship between baseline dementia and one-year mortality after surgery. METHODS: Patients age 65 years and older undergoing hip fracture repair surgery at John Hopkins Bayview Medical Center between 1999 and 2009 were eligible for this prospective cohort study. Baseline probable dementia was defined as either preoperatively diagnosed dementia per geriatrician or score less than 24 on the Mini-Mental State Examination. Delirium was assessed using the Confusion Assessment Method. Four cognitive groups were defined: 1) neither probable dementia nor delirium (NDD), 2) probable dementia only, 3) delirium only, or 4) delirium superimposed on dementia (DSD). Primary outcome of mortality was obtained through hospital records, obituaries, the National Death Index, and Social Security Death Index. RESULTS: The current sample comprises 466 subjects (average age: 80.8 ± 7.0 years; 73.6% female). Of these, 77 (17%) were categorized as DSD, 68 (15%) probable dementia only, 73 (16%) delirium only, and 248 (53%) NDD. Cox regression revealed that DSD subjects had a significantly higher hazard of one-year mortality than NDD subjects (hazard ratio [HR]: 1.71, 95% CI: 1.06, 2.77) after adjusting for age, sex, medical comorbidity, and surgery duration. Trends toward greater mortality for probable-dementia and delirium only subjects were not significant (HR: 1.42 [95% CI: 0.80, 2.52] and 1.12 [95% CI: 0.64, 1.95], respectively). CONCLUSIONS: Delirium after hip fracture repair surgery in patients with preoperative dementia modifies the risk of mortality over the first postoperative year. Patients with DSD have a nearly two-fold greater odds of one-year mortality than those without dementia or delirium.

On the feasibility of polyurethane based 3D dosimeters with optical CT for dosimetric verification of low energy photon brachytherapy seeds.

PURPOSE: To investigate the feasibility of and challenges yet to be addressed to measure dose from low energy (effective energy <50 keV) brachytherapy sources (Pd-103, Cs-131, and I-125) using polyurethane based 3D dosimeters with optical CT. METHODS: The authors' evaluation used the following sources: models 200 (Pd-103), CS-1 Rev2 (Cs-131), and 6711 (I-125). The authors used the Monte Carlo radiation transport code MCNP5, simulations with the ScanSim optical tomography simulation software, and experimental measurements with PRESAGE(®) dosimeters/optical CT to investigate the following: (1) the water equivalency of conventional (density = 1.065 g/cm(3)) and deformable (density = 1.02 g/cm(3)) formulations of polyurethane dosimeters, (2) the scatter conditions necessary to achieve accurate dosimetry for low energy photon seeds, (3) the change in photon energy spectrum within the dosimeter as a function of distance from the source in order to determine potential energy sensitivity effects, (4) the optimal delivered dose to balance optical transmission (per projection) with signal to noise ratio in the reconstructed dose distribution, and (5) the magnitude and characteristics of artifacts due to the presence of a channel in the dosimeter. Monte Carlo simulations were performed using both conventional and deformable dosimeter formulations. For verification, 2.8 Gy at 1 cm was delivered in 92 h using an I-125 source to a PRESAGE(®) dosimeter with conventional formulation and a central channel with 0.0425 cm radius for source placement. The dose distribution was reconstructed with 0.02 and 0.04 cm(3) voxel size using the Duke midsized optical CT scanner (DMOS). RESULTS: While the conventional formulation overattenuates dose from all three sources compared to water, the current deformable formulation has nearly water equivalent attenuation properties for Cs-131 and I-125, while underattenuating for Pd-103. The energy spectrum of each source is relatively stable within the first 5 cm especially for I-125. The inherent assumption of radial symmetry in the TG43 geometry leads to a linear increase in sample points within the 3D dosimeter as a function of distance away from the source, which partially offsets the decreasing signal. Simulations of dose reconstruction using optical CT showed the feasibility of reconstructing dose out to a radius of 10 cm without saturating projection images using an optimal dose and high dynamic range scanning; the simulations also predicted that reconstruction artifacts at the channel surface due to a small discrepancy in refractive index should be negligible. Agreement of the measured with calculated radial dose function for I-125 was within 5% between 0.3 and 2.5 cm from the source, and the median difference of measured from calculated anisotropy function was within 5% between 0.3 and 2.0 cm from the source. CONCLUSIONS: 3D dosimetry using polyurethane dosimeters with optical CT looks to be a promising application to verify dosimetric distributions surrounding low energy brachytherapy sources.

A low-cost, high-performance system for fluorescence lateral flow assays.

We demonstrate a fluorescence lateral flow system that has excellent sensitivity and wide dynamic range. The illumination system utilizes an LED, plastic lenses and plastic and colored glass filters for the excitation and emission light. Images are collected on an iPhone 4. Several fluorescent dyes with long Stokes shifts were evaluated for their signal and nonspecific binding in lateral flow. A wide range of values for the ratio of signal to nonspecific binding was found, from 50 for R-phycoerythrin (R-PE) to 0.15 for Brilliant Violet 605. The long Stokes shift of R-PE allowed the use of inexpensive plastic filters rather than costly interference filters to block the LED light. Fluorescence detection with R-PE and absorbance detection with colloidal gold were directly compared in lateral flow using biotinylated bovine serum albumen (BSA) as the analyte. Fluorescence provided linear data over a range of 0.4-4,000 ng/mL with a 1,000-fold signal change while colloidal gold provided non-linear data over a range of 16-4,000 ng/mL with a 10-fold signal change. A comparison using human chorionic gonadotropin (hCG) as the analyte showed a similar advantage in the fluorescent system. We believe our inexpensive yet high-performance platform will be useful for providing quantitative and sensitive detection in a point-of-care setting.

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry.

PURPOSE: To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. METHODS: For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 10(9) photon histories from a (137)Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for (137)Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE(®) dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)(3) isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. RESULTS: The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D γ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D(2cc) to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. CONCLUSIONS: Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.