Effectiveness of three Vitamin D dosing protocols on raising and maintaining blood serum levels of 25-hydroxyvitamin D over a three-month period: a randomized, prospective study.

INTRODUCTION: Vitamin D has gained attention in the medical community due to its critical role in calcium homeostasis and overall bone health. No standard vitamin D dosing protocol in fracture care has been established for patients deficient in 25-hydroxyvitamin D. This prospective and randomized study aimed to find a dosing regimen that would safely achieve and maintain a therapeutic level of 25-hydroxyvitamin D in deficient patients over three months. MATERIALS AND METHODS: Between June 2016 and May 2017, 48 patients with baseline total 25-hydroxyvitamin D less than 30.0 ng/mL were randomly assigned to either group one (one dose of 100,000 international units (IU) of Vitamin D2) or group 2 (100,000 IU of Vitamin D2 once weekly for twelve weeks) or group 3 (50,000 IU of Vitamin D2 daily for ten days followed by 2,000 IU of Vitamin D3 daily for 74 days). Baseline serum levels were drawn followed by interval levels at week 2, 6 and 12. The primary outcome was to determine which protocol could achieve and maintain therapeutic levels of total 25-hydroxyvitamin D over the course of three months. Our secondary outcome was to monitor for negative side effects. RESULTS: Group 1 did not show any statistically significant increase in serum levels and had no reported side effects. There was a statistically significant increase in serum total 25-hydroxyvitamin D in group 2 between all-time points except between weeks 6 and 12. Two (12.5%) participants in group 2 reported side effects. Group 3 had the greatest change in serum levels from weeks 0 to 2 but had a significant decrease between weeks 2 and 6. No change was seen between weeks 6 and 12. Three (17.5%) participants in group 3 reported side effects. CONCLUSIONS: Group 2 sustained and maintained a satisfactory level of total 25-hydroxyvitamin D over three months without any severe side effects.

Electroencephalography Signatures for Conditioned Pain Modulation and Pain Perception in Nonspecific Chronic Low Back Pain-An Exploratory Study.

Conditioned pain modulation (CPM) can discriminate between healthy and chronic pain patients. However, its relationship with neurophysiological pain mechanisms is poorly understood. Brain oscillations measured by electroencephalography (EEG) might help gain insight into this complex relationship. OBJECTIVE: To investigate the relationship between CPM response and self-reported pain intensity in non-specific chronic low back pain (NSCLBP) and explore respective EEG signatures associated to these mechanisms. DESIGN: Cross-sectional analysis. PARTICIPANTS: Thirty NSCLBP patients participated. METHODS: Self-reported low back pain, questionnaires, mood scales, CPM (static and dynamic quantitative sensory tests), and resting surface EEG data were collected and analyzed. Linear regression models were used for statistical analysis. RESULTS: CPM was not significantly correlated with self-reported pain intensity scores. Relative power of EEG in the beta and high beta bands as recorded from the frontal, central, and parietal cortical areas were significantly associated with CPM. EEG relative power at delta and theta bands as recorded from the central area were significantly correlated with self-reported pain intensity scores while controlling for self-reported depression. CONCLUSIONS: Faster EEG frequencies recorded from pain perception areas may provide a signature of a potential cortical compensation caused by chronic pain states. Slower EEG frequencies may have a critical role in abnormal pain processing.

Monte Carlo modeling of the Elekta Versa HD and patient dose calculation with EGSnrc/BEAMnrc.

INTRODUCTION: Numerous studies have proven the Monte Carlo method to be an accurate means of dose calculation. Although there are several commercial Monte Carlo treatment planning systems (TPSs), some clinics may not have access to these resources. We present a method for routine, independent patient dose calculations from treatment plans generated in a commercial TPS with our own Monte Carlo model using free, open-source software. MATERIALS AND METHODS: A model of the Elekta Versa HD linear accelerator was developed using the EGSnrc codes. A MATLAB script was created to take clinical patient plans and convert the DICOM RTP files into a format usable by EGSnrc. Ten patients' treatment plans were exported from the Monaco TPS to be recalculated using EGSnrc. Treatment simulations were done in BEAMnrc, and doses were calculated using Source 21 in DOSXYZnrc. Results were compared to patient plans calculated in the Monaco TPS and evaluated in Verisoft with a gamma criterion of 3%/2 mm. RESULTS: Our Monte Carlo model was validated within 1%/1-mm accuracy of measured percent depth doses and profiles. Gamma passing rates ranged from 82.1% to 99.8%, with 7 out of 10 plans having a gamma pass rate over 95%. Lung and prostate patients showed the best agreement with doses calculated in Monaco. All statistical uncertainties in DOSXYZnrc were less than 3.0%. CONCLUSION: A Monte Carlo model for routine patient dose calculation was successfully developed and tested. This model allows users to directly recalculate DICOM RP files containing patients' plans that have been exported from a commercial TPS.

Preemptive Femoral-Femoral Crossover Grafting of Artery and Vein Before Pelvic Exenterative Surgery for Locally Advanced and Recurrent Pelvic Malignancy Involving the Aortoiliac Axis.

INTRODUCTION: Achieving a negative resection through a pelvic exenteration for a recurrent or an advanced pelvic malignancy offers the potential for cure. Exenterative surgical units have expanded the boundaries and redefined what constitutes resectable disease through improved surgical technique. In selected cases, contiguous tumor involvement of the aortoiliac axis requires en bloc resection and subsequent vessel reconstruction. However, vascular reconstruction can be challenging in a contaminated field during an extended radical resection. TECHNIQUE: The aim of this Technical Note is to describe a novel method in the management of patients with recurrent or advanced pelvic malignancy involving the aortoiliac axis by performing preemptive femoral-femoral arterial and venous crossover grafts, with adjunctive arteriovenous loop fistula formation before undergoing an extended radical pelvic resection 4 weeks later. RESULTS: Four patients have undergone preemptive femoral-femoral arterial and venous crossover grafts at our institution (median age = 60 y (range, 47-66 y); 2 women). There were no early complications, and all of the patients subsequently underwent extended radical pelvic resections for a pelvic malignancy. CONCLUSIONS: Preemptive vascular reconstruction before major pelvic surgery reduces the risk of graft infection because this method avoids the wounds being contaminated by GI or genitourinary organisms. Other advantages to this technique include a reduction in the overall operating time for the pelvic exenteration, a significant reduction in the ischemia time to the lower limbs, and ensuring that the grafts are patent before embarking on major intra-abdominal surgery.

On the evaluation of mobile target trajectory between four-dimensional computer tomography and four-dimensional cone-beam computer tomography.

PURPOSE: For mobile lung tumors, four-dimensional computer tomography (4D CT) is often used for simulation and treatment planning. Localization accuracy remains a challenge in lung stereotactic body radiation therapy (SBRT) treatments. An attractive image guidance method to increase localization accuracy is 4D cone-beam CT (CBCT) as it allows for visualization of tumor motion with reduced motion artifacts. However, acquisition and reconstruction of 4D CBCT differ from that of 4D CT. This study evaluates the discrepancies between the reconstructed motion of 4D CBCT and 4D CT imaging over a wide range of sine target motion parameters and patient waveforms. METHODS: A thorax motion phantom was used to examine 24 sine motions with varying amplitudes and cycle times and seven patient waveforms. Each programmed motion was imaged using 4D CT and 4D CBCT. The images were processed to auto segment the target. For sine motion, the target centroid at each phase was fitted to a sinusoidal curve to evaluate equivalence in amplitude between the two imaging modalities. The patient waveform motion was evaluated based on the average 4D data sets. RESULTS: The mean difference and root-mean-square-error between the two modalities for sine motion were -0.35 ± 0.22 and 0.60 mm, respectively, with 4D CBCT slightly overestimating amplitude compared with 4D CT. The two imaging methods were determined to be significantly equivalent within ±1 mm based on two one-sided t tests (p < 0.001). For patient-specific motion, the mean difference was 1.5 ± 2.1 (0.8 ± 0.6 without outlier), 0.4 ± 0.3, and 0.8 ± 0.6 mm for superior/inferior (SI), anterior/posterior (AP), and left/right (LR), respectively. CONCLUSION: In cases where 4D CT is used to image mobile tumors, 4D CBCT is an attractive localization method due to its assessment of motion with respect to 4D CT, particularly for lung SBRT treatments where accuracy is paramount.

Deep learning-based survival analysis for brain metastasis patients with the national cancer database.

PURPOSE: Prognostic indices such as the Brain Metastasis Graded Prognostic Assessment have been used in clinical settings to aid physicians and patients in determining an appropriate treatment regimen. These indices are derivative of traditional survival analysis techniques such as Cox proportional hazards (CPH) and recursive partitioning analysis (RPA). Previous studies have shown that by evaluating CPH risk with a nonlinear deep neural network, DeepSurv, patient survival can be modeled more accurately. In this work, we apply DeepSurv to a test case: breast cancer patients with brain metastases who have received stereotactic radiosurgery. METHODS: Survival times, censorship status, and 27 covariates including age, staging information, and hormone receptor status were provided for 1673 patients by the NCDB. Monte Carlo cross-validation with 50 samples of 1400 patients was used to train and validate the DeepSurv, CPH, and RPA models independently. DeepSurv was implemented with L2 regularization, batch normalization, dropout, Nesterov momentum, and learning rate decay. RPA was implemented as a random survival forest (RSF). Concordance indices of test sets of 140 patients were used for each sample to assess the generalizable predictive capacity of each model. RESULTS: Following hyperparameter tuning, DeepSurv was trained at 32 min per sample on a 1.33 GHz quad-core CPU. Test set concordance indices of 0.7488 ± 0.0049, 0.6251 ± 0.0047, and 0.7368 ± 0.0047, were found for DeepSurv, CPH, and RSF, respectively. A Tukey HSD test demonstrates a statistically significant difference between the mean concordance indices of the three models. CONCLUSION: Our results suggest that deep learning-based survival prediction can outperform traditional models, specifically in a case where an accurate prognosis is highly clinically relevant. We recommend that where appropriate data are available, deep learning-based prognostic indicators should be used to supplement classical statistics.

Self-management intervention for head and neck cancer couples: Results of a randomized pilot trial.

BACKGROUND: Patients with head and neck cancer (HNC) experience significant physical and psychological morbidity during radiotherapy (RT) that contributes to treatment interruptions and a poor quality of life. Although spouses/partners can help by encouraging patient self-management (eg, self-care) during RT, they often experience high psychological distress rates, lack basic health care knowledge and skills, and report increased marital conflict regarding patient self-management. The current pilot study examined the feasibility and acceptability of a 6-session telephone-based intervention called Spouses coping with the Head And neck Radiation Experience (SHARE), which teaches self-management, communication, and coping skills to patients with HNC and their spouses. The treatment effects of SHARE compared with usual medical care (UMC) in controlling patient physical symptoms and improving patient/spouse psychological and marital functioning also were examined. METHODS: Thirty patients who initiated RT and their spouses (60 participants; 40% of whom were racial/ethnic minorities) were randomized to SHARE or UMC, and preintervention and postintervention assessments were completed. RESULTS: Solid recruitment (70%) and low attrition rates (7%) demonstrated feasibility. Strong program evaluations and homework completion rates (72%) supported acceptability. Significant treatment effects (medium in magnitude) were observed for SHARE compared with UMC with regard to HNC-specific physical symptom burden (Cohen's d, -0.89) and symptom interference (Cohen's d, -0.86). Medium to large effects favoring SHARE also were found for patient and spouse depressive symptoms (Cohen's d, -0.84) and cancer-specific distress (Cohen's d, -1.05). CONCLUSIONS: The findings of the current study support the feasibility, acceptability, and preliminary efficacy of SHARE. They also suggest that programs that empower HNC couples with the necessary skills to coordinate care and manage the challenges of RT together hold great promise for controlling a patient's physical symptoms and improving the psychological functioning of both partners.

Percutaneous Axillary Artery Access in Complex Endovascular Aortic Repair.

PURPOSE: This study was designed to assess the feasibility and safety of percutaneous axillary access in complex endovascular aortic repair (EVAR) with use of a percutaneous closure device. MATERIALS AND METHODS: All patients undergoing percutaneous axillary artery access between 2012 and 2017 were included. Left percutaneous axillary access was the sole antegrade aortic approach used. Patient and intervention characteristics were documented. Mortality, procedural success, technical success, peri- and postoperative complications, and repeat interventions were examined. A total of 25 percutaneous axillary access procedures were performed in 23 patients. The mean age of the treated patients was 72.2 years, and 71% were male. Percutaneous axillary access was obtained for a variety of indications (chimney EVAR, thoracoabdominal aortic aneurysm repair, thoracic EVAR, and type B dissections). Vascular access sheath sizes ranged from 6 F to 12 F. RESULTS: The procedural success rate was 96%. Technical success of vascular closure was 100%. The perioperative access complication rate was 8%: 1 dissection of the axillary artery and 1 stenosis occurred. No hematoma, hemorrhage, or neuropathies were seen. One access-related repeat intervention had to be performed. The 30-d mortality rate was 4%. CONCLUSIONS: Direct puncture and percutaneous closure of the axillary artery for complex aortic procedures is safe and feasible.

Concomitant Hybrid Arch Vessel Reconstruction and Intracranial Clot Retrieval in Takayasu's Arteritis Presenting with Acute Cerebral Ischemia: A Case Report.

BACKGROUND: Type 1 Takayasu's arteritis (TA) predominantly affects the supra-aortic branches. Occlusive disease can cause catastrophic complications such as stroke and death. Open and endovascular techniques of revascularization are described for extracranial disease. There is currently no default choice of surgical intervention. Furthermore, the management of distal intracranial complications has not been described. METHODS: A 25-year-old woman with known TA on immunosuppression was presented with acute left middle cerebral artery (MCA) stroke. Computed tomography angiogram and formal cerebral digital subtraction angiography demonstrated critical stenoses or occlusion of all arch vessels except for the left subclavian artery (SCA), which was also stenosed at the origin. The left vertebral artery was the sole inflow to the brain. Furthermore, there was acute embolus in M1 of MCA and A1 of the anterior cerebral artery (ACA). Surgical access was achieved by bilateral common carotid artery (CCA) and left SCA exposures. Extracranial revascularization was performed using a hybrid technique: (i) left SCA covered stent; (ii) left SCA to right CCA bypass; (iii) left CCA thrombectomy; (iv) left CCA covered stent; and (v) left CCA interposition bypass. This was immediately followed by clot retrieval in the MCA and ACA territory for intracranial revascularization. RESULTS: There were no major postoperative complications and the patient made an excellent neurologic recovery. CONCLUSIONS: Hybrid vascular reconstruction for extracranial disease with concomitant clot retrieval for intracranial disease is a novel approach to achieving emergency revascularization in active TA.

The Effect of Pelvic Tilt and Femoral Head Size on Hip Range-of-Motion to Impingement.

BACKGROUND: About 50%-70% of dislocators have cups placed within so-called "safe zones." It has been postulated that factors such as femoral head size and pelvic tilt, obliquity, or rotation may influence postoperative stability. Therefore, we assessed varying degrees of pelvic tilt and head sizes on the range of motion (ROM) to impingement. METHODS: A hip simulator was used to import models of 10 subjects who performed object pickup, squatting, and low-chair rising. Parameters were set for pelvic tilt, stem version, and the specific motions as defined by the subjects. Femur-to-pelvis relative motions were determined for abduction/adduction, internal/external rotation, and flexion/extension. Varying tilt angles were tested. Thirty-two millimeter and 36-mm head with a standard cup and 42-mm dual mobility cup were tested. Cup orientations for abduction and anteversion combinations were chosen, and computations of minimum clearances or impingement between components were made. RESULTS: The ROM to impingement varied with the different pelvic tilts and femoral head sizes and with the different motions. The larger the head size, the larger the impingement-free ROM. Negative 10° of pelvic tilt led to the largest impingement-free zone, whereas 10° of forward tilt was associated with fewer impingement-free cup anteversion and abduction angle combinations. Variations in pelvic tilt had the greatest influence on object pickup and affected the impingement-free "safe zone." CONCLUSION: Targets for impingement-free motion may be smaller when considering varying pelvic tilts and femoral head sizes, particularly for certain activities, such as object pickup. These findings may indicate the need for more individualized patient planning.

Cryotherapy Treatment After Arthroscopic Knee Debridement and ACL Reconstruction: A Review.

Pain, swelling, and inflammation of the knee joint and its surrounding soft-tissue structures are common during the postoperative period after arthroscopic knee debridement and anterior cruciate ligament reconstruction. These challenges can make patient recovery difficult immediately after surgery. Several options exist, however, to help patients overcome these challenges. Cryotherapy has been noted to decrease pain, swelling, and inflammation. However, while a number of studies exist characterizing the use of cryotherapy after knee surgery, no definitive cryotherapy devices and modalities have been identified. Therefore, the purpose of this review was to evaluate randomized controlled trials to assess the use of cryotherapy after: 1) arthroscopic debridement; and 2) anterior cruciate ligament reconstruction.

Radiographic Classification Systems for Osteonecrosis of the Knee: A Review of Literature.

Knee osteonecrosis is a rare, yet debilitating disease that can lead to knee joint destruction and can be associated with significant pain and disability. Various imaging modalities have different roles in the diagnosis, staging, management, and determination of the prognosis in knee osteonecrosis. Plain radiographic images can show gross joint destruction and secondary arthritic changes. In addition, magnetic resonance imaging (MRI) has become the gold-standard imaging modality to diagnose osteonecrosis. Multiple classification systems have been developed for knee osteonecrosis based on these imaging modalities. The goal of these systems is to stage the disease and guide management. Better understanding of the pattern of the lesions and its morphometric characteristics may allow surgeons to reach a better consensus regarding the timing of surgical treatment, choice of implant, and overall disease prognosis in these unique patients. Due to the relative paucity of evidence, this review was conducted to evaluate different radiological classification systems utilized in osteonecrosis of the knee joint.

Axillary Artery Injury Associated with Proximal Humeral Fractures: Review of Long-Term Vascular, Orthopedic, and Neurologic Outcomes.

BACKGROUND: Fracture and dislocation of the proximal humerus is common. It is associated with a number of vascular, neurologic, and orthopedic complications; these include brachial plexopathy and avascular necrosis (AVN) of the humeral head. These complications are rare but can potentially cause severe disability to patients; however, they remain poorly described in the literature. To describe vascular, orthopedic, and neurologic outcomes after axillary artery repair, in patients with proximal humeral fractures or dislocations. METHODS: We conducted a retrospective review of patients admitted to 2 tertiary trauma centers in Victoria, Australia, with fracture or dislocation of the proximal humerus and associated axillary artery injury. Patients were selected according to guidelines for trauma call or alert and the presence of high-risk mechanism of injury. Data on vascular, orthopedic, and neurologic complications were collected. RESULTS: Twenty-one patients were identified. Injury to the first part of the axillary artery was noted in 11 patients (52%). Brachial plexus exploration was performed in 17 patients (81%). Four patients (19%) underwent nerve repair. Long-term neurologic recovery was universally poor. Major orthopedic complications included AVN of the humeral head, delayed union, and the need for prosthesis or arthrodesis. Eleven patients (52%) received upper limb fasciotomy. Five patients (24%) underwent delayed secondary upper limb amputation. CONCLUSIONS: There was an unusually high rate of injuries to the first part of the axillary artery. Close clinical observation is recommended for such patients. AVN of the humeral head and brachial plexopathy remain significant and debilitating complications.

Treatment of localized hepatocellular carcinoma: resection vs. ablation vs. radiation.

Hepatocellular carcinoma (HCC) is a common malignancy with many patients presenting with local disease. As of date, the use of radiation is not included in the commonly utilized Barcelona Clinic Liver Cancer (BCLC) classification but is in the National Comprehensive Cancer Network guidelines. Radiation can volumetrically cover the entire tumor and with novel technologic advances can be administered non-invasively with excellent clinical outcomes with few adverse events. The gold standard for localized early HCC (such as BCLC-A) is resection or transplantation. In patients who are not candidates for surgical treatment, locoregional therapy should be considered as an optimal therapy for these patients. Tumor ablation techniques such as microwave ablation (MWA) and radiofrequency ablation (RFA) are excellent tools to control local disease or bridge to transplantation. Should these not be possible though then ablation with external beam radiation is also capable of yielding comparable local control and serve as a bridge to transplant without worse rates of adverse events. For tumors that meet Milan criteria for transplantation, in comparison to transarterial chemoembolization (TACE), there is considerable randomized evidence demonstrating better local control, less adverse events, better progression-free survival (PFS), and less costly. It can be utilized as a bridge in Barcelona liver class B. For larger localized tumors though (extrahepatic disease or vascular invasion like BCLC-C), stereotactic body radiation therapy (SBRT) is shown via a randomized clinical trial to have a survival benefit, local control benefit, and no worse adverse events compared to systemic therapy. In this setting, it should be considered the local consolidation standard of care.

Spatially distributed atmospheric boundary layer properties in Houston - A value-added observational dataset.

In 2022, Houston, TX became a nexus for field campaigns aiming to further our understanding of the feedbacks between convective clouds, aerosols and atmospheric boundary layer (ABL) properties. Houston's proximity to the Gulf of Mexico and Galveston Bay motivated the collection of spatially distributed observations to disentangle coastal and urban processes. This paper presents a value-added ABL dataset derived from observations collected by eight research teams over 46 days between 2 June - 18 September 2022. The dataset spans 14 sites distributed within a ~80-km radius around Houston. Measurements from three types of instruments are analyzed to objectively provide estimates of nine ABL parameters, both thermodynamic (potential temperature, and relative humidity profiles and thermodynamic ABL depth) and dynamic (horizontal wind speed and direction, mean vertical velocity, updraft and downdraft speed profiles, and dynamical ABL depth). Contextual information about cloud occurrence is also provided. The dataset is prepared on a uniform time-height grid of 1 h and 30 m resolution to facilitate its use as a benchmark for forthcoming numerical simulations and the fundamental study of atmospheric processes.

The evolution of Big Data in neuroscience and neurology.

Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started to transform the fields of Neuroscience and Neurology. Scientists and clinicians are collaborating in global alliances, combining diverse datasets on a massive scale, and solving complex computational problems that demand the utilization of increasingly powerful computational resources. This Big Data revolution is opening new avenues for developing innovative treatments for neurological diseases. Our paper surveys Big Data's impact on neurological patient care, as exemplified through work done in a comprehensive selection of areas, including Connectomics, Alzheimer's Disease, Stroke, Depression, Parkinson's Disease, Pain, and Addiction (e.g., Opioid Use Disorder). We present an overview of research and the methodologies utilizing Big Data in each area, as well as their current limitations and technical challenges. Despite the potential benefits, the full potential of Big Data in these fields currently remains unrealized. We close with recommendations for future research aimed at optimizing the use of Big Data in Neuroscience and Neurology for improved patient outcomes. Supplementary Information: The online version contains supplementary material available at 10.1186/s40537-023-00751-2.

Major vascular reconstruction in colorectal adenocarcinoma and retroperitoneal sarcoma: A retrospective study of safety and margins in a tertiary referral centre.

BACKGROUND: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures. METHODS: Patients undergoing curative intent EVRR for advanced CRC and RPS between 2014 and 2021 at a tertiary centre were included. Morbidity, margins, recurrence, and survival were evaluated. RESULTS: 24 patients underwent EVRR with 48 reconstructions (11 CRC and 13 RPS). For CRC, 100% of patients underwent Iliac system reconstructions. For RPS, inferior vena cava reconstructions were the most common (69.2%). There were 2 arterial and 1 venous graft thromboses. Primary graft patency was 89.4% arterial and 93.1% venous, while secondary patency was 100% arterial and 96.5% venous at last follow up. 1 venous and 1 arterial graft required reoperation for bleeding. There were no compromised limbs. Major complications occurred in 6 patients (25.0%) with no observed difference between CRC and RPS (OR 0.43 95%CI[0.60,3.19], P = 0.41). R1 margins occurred 1 CRC (90.9%) and 3 RPS (76.9%), with no R2 resections. All vascular resection margins were clear. There were 6 CRC (50%) and 4 RPS (33.3%) recurrences. Median recurrence time was 20.9 months for CRC and 'not yet reached' for RPS. Median follow-up was 19.4 months for CRC and 21.4 months for RPS. CONCLUSION: EVRR for locally advanced CRC or RPS is safe and achieves favorable R0 resection rates. CRC patients with major vascular invasion can still be considered for curative intent surgery. Larger cohorts with longer follow up are needed to assess oncologic outcomes.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

Frail patients having vascular surgery during the early COVID-19 pandemic experienced high rates of adverse perioperative events and amputation.

BACKGROUND: Frailty predicts adverse perioperative outcomes and increased mortality in patients having vascular surgery. Frailty assessment is a potential tool to inform resource allocation, and shared decision-making about vascular surgery in the resource constrained COVID-19 pandemic environment. This cohort study describes the prevalence of frailty in patients having vascular surgery and the association between frailty, mortality and perioperative outcomes. METHODS: The COVID-19 Vascular Service in Australia (COVER-AU) prospective cohort study evaluates 30-day and six-month outcomes for consecutive patients having vascular surgery in 11 Australian vascular units, March-July 2020. The primary outcome was mortality, with secondary outcomes procedure-related outcomes and hospital utilization. Frailty was assessed using the nine-point visual Clinical Frailty Score, scores of 5 or more considered frail. RESULTS: Of the 917 patients enrolled, 203 were frail (22.1%). The 30 day and 6 month mortality was 2.0% (n = 20) and 5.9% (n = 35) respectively with no significant difference between frail and non-frail patients (OR 1.68, 95%CI 0.79-3.54). However, frail patients stayed longer in hospital, had more perioperative complications, and were more likely to be readmitted or have a reoperation when compared to non-frail patients. At 6 months, frail patients had twice the odds of major amputation compared to non-frail patients, after adjustment (OR 2.01; 95% CI 1.17-3.78), driven by a high rate of amputation during the period of reduced surgical activity. CONCLUSION: Our findings highlight that older, frail patients, experience potentially preventable adverse outcomes and there is a need for targeted interventions to optimize care, especially in times of healthcare stress.

Characterization of ground-based atmospheric pollution and meteorology sampling stations during the Lake Michigan Ozone Study 2017.

The Lake Michigan Ozone Study 2017 (LMOS 2017) in May and June 2017 enabled study of transport, emissions, and chemical evolution related to ozone air pollution in the Lake Michigan airshed. Two highly instrumented ground sampling sites were part of a wider sampling strategy of aircraft, shipborne, and ground-based mobile sampling. The Zion, Illinois site (on the coast of Lake Michigan, 67 km north of Chicago) was selected to sample higher NOx air parcels having undergone less photochemical processing. The Sheboygan, Wisconsin site (on the coast of Lake Michigan, 211 km north of Chicago) was selected due to its favorable location for the observation of photochemically aged plumes during ozone episodes involving southerly winds with lake breeze. The study encountered elevated ozone during three multiday periods. Daytime ozone episode concentrations at Zion were 60 ppb for ozone, 3.8 ppb for NOx, 1.2 ppb for nitric acid, and 8.2 µg m-3 for fine particulate matter. At Sheboygan daytime, ozone episode concentrations were 60 ppb for ozone, 2.6 ppb for NOx, and 3.0 ppb for NOy. To facilitate informed use of the LMOS 2017 data repository, we here present comprehensive site description, including airmass influences during high ozone periods of the campaign, overview of meteorological and pollutant measurements, analysis of continuous emission monitor data from nearby large point sources, and characterization of local source impacts from vehicle traffic, large point sources, and rail. Consistent with previous field campaigns and the conceptual model of ozone episodes in the area, trajectories from the southwest, south, and lake breeze trajectories (south or southeast) were overrepresented during pollution episodes. Local source impacts from vehicle traffic, large point sources, and rail were assessed and found to represent less than about 15% of typical concentrations measured. Implications for model-observation comparison and design of future field campaigns are discussed.Implications: The Lake Michigan Ozone Study 2017 (LMOS 2017) was conducted along the western shore of Lake Michigan, and involved two well-instrumented coastal ground sites (Zion, IL, and Sheboygan, WI). LMOS 2017 data are publicly available, and this paper provides detailed site characterization and measurement summary to enable informed use of repository data. Minor local source impacts were detected but were largely confined to nighttime conditions of less interest for ozone episode analysis and modeling. The role of these sites in the wider field campaign and their detailed description facilitates future campaign planning, informed data repository use, and model-observation comparison.