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BACKGROUND CONTEXT Improving value is an established point of emphasis to reduce the rapidly rising health care costs in the United States. Back pain is a major driver of costs with a substantial fraction caused by lumbar radiculopathy. The most common surgical treatment for lumbar radiculopathy is microdiscectomy. Research is sparse regarding variables driving cost in microdiscectomies and often limited by cost data derived from payer-based Medicare data. PURPOSE To identify targets for cost reduction by determining variables associated with significant cost variation in microdiscectomies, using cost data derived from the Value Driven Outcomes tool and actual system costs. STUDY DESIGN Single-center, retrospective study of prospectively collected registry data. PATIENT SAMPLE Six hundred twenty-two patients identified by CPT code and manually screened for initial, unilateral, single-level lumbar discectomy performed between 2014 and 2018 at a single institution. OUTCOME MEASURES Primary outcome measures include total direct cost, clinical length of stay, and OR minutes. Total Direct Cost was further differentiated into facility and nonfacility costs. METHODS Univariate and multivariate generalized linear models (GLM) were used to identify variables associated with variation in primary outcome measures. Costs were normalized by mean cost for patients with normal body mass index (BMI) and a healthy American Society of Anesthesiologists (ASA) classification. Average marginal effects were reported as percentage of normalized costs. RESULTS Advanced age, male gender, Hispanic, black, unemployment, obesity, higher ASA class, insurance status, and being retired were positively associated with costs in univariate analysis. Asian, Native American, outpatient procedures, and being a student were associated with decreases in costs. In multivariate analysis, we found that obesity led to higher average marginal total direct (9%), total facility (15%), and facility OR costs (22%), as well as 24 more OR minutes per surgery. While being overweight was not associated with greater total direct costs, it was associated with higher total facility (8%), and facility OR costs (12%), with 11 more OR minutes per surgery. Age was associated with a longer LOS but not with OR costs. As expected, outpatient surgical costs, LOS, and OR time were significantly lower than inpatient procedures. Severe systematic disease was associated with greater total and nonfacility costs. In addition, Medicare patients had higher facility costs (14%) compared to privately insured patients. CONCLUSIONS Significant drivers of total direct cost in multivariate GLM analysis were obesity, severe systemic disease and inpatient surgery. Average LOS was increased due to age and inpatient status, conversely it was decreased by unemployment and retirement. Significant variables in OR time were male sex, Hispanic race and both obese and overweight BMIs.

BACKGROUND AND AIMS: In a United States randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72%-XR-NTX vs. 94%-BUP-NX). This led to higher relapse rates and average healthcare costs among XR-NTX participants. This study estimated the extent to which a more efficient model of XR-NTX induction would improve the economic value of XR-NTX relative to BUP-NX. DESIGN: This was a retrospective secondary analysis of CTN-0051 trial data, including follow up data over 24–36 weeks. SETTING: Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the USA. PARTICIPANTS: 283 participants randomized to receive XR-NTX. MEASUREMENTS: Efficiency was estimated using a multivariable generalized-structural-equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the healthcare sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS: Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5,317 more than that of BUP-NX (p=0.01) to a non-statistically-significant difference of $1,016 (p=0.63). QALYs gained remained similar across arms. CONCLUSION: Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the healthcare sector perspective over 24–36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.

Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02734-8.

reSET-O is a Food and Drug Administration-cleared prescription digital therapeutic (PDT) indicated to improve outpatient-treatment retention of patients with opioid use disorder (OUD). This study examined the cost-effectiveness and budget impact of reSET-O in conjunction with treatment as usual (reSET-O + TAU) relative to TAU.Adult patients with ≥1 OUD diagnosis, treated with buprenorphine from 1 January 2015 to 30 March 2018, were identified from Truven Health MarketScan Commercial and Medicare Supplemental Research Databases. Twelve-week healthcare resource utilization (HCRU) costs for patients categorized as adherent and nonadherent to buprenorphine treatment were estimated. Total 12-week costs included OUD treatment and other HCRU costs. The cost-effectiveness of reSET-O + TAU was modeled in accordance with prior clinical trial outcomes. The 12-week budget impact of reSET-O was modeled for a 1 million-member healthcare plan.Higher buprenorphine adherence was associated with lower HCRU costs in claims data. Twelve-week per-patient total costs were $305 more for those receiving reSET-O + TAU than those receiving TAU. The incremental cost-effectiveness ratio was $18.70 per 1 percentage-point increase in the treatment retention rate. The probability that reSET-O + TAU would be considered cost-effective was over 92% for willingness-to-pay thresholds of $6,000 or more. The 12-week budget impact of reSET-O was $8,908, translating to $0.003 per member per month.The findings of the cost-effectiveness and budget impact modeling are limited by the assumptions of the models due to uncertainty around some inputs. While no model is free of bias, the inputs for this model were carefully selected to reflect contemporary treatment patterns.Depending on the payer's willingness to pay, reSET-O may be cost-effective in increasing buprenorphine treatment retention rates. reSET-O results in an approximate budget impact of $0.003 per member per month, depending on market share and the prevalence of the population receiving treatment for OUD.

Background Craniosynostosis is the premature fusion of ≥1 cranial sutures and often requires surgical intervention. Surgery may involve extensive osteotomies, which can lead to substantial blood loss. Currently, there are no consensus recommendations for guiding blood conservation or transfusion in this patient population. The aim of this study is to develop a machine-learning model to predict blood product transfusion requirements for individual pediatric patients undergoing craniofacial surgery. Methods Using data from 2143 patients in the Pediatric Craniofacial Surgery Perioperative Registry, we assessed 6 machine-learning classification and regression models based on random forest, adaptive boosting (AdaBoost), neural network, gradient boosting machine (GBM), support vector machine, and elastic net methods with inputs from 22 demographic and preoperative features. We developed classification models to predict an individual's overall need for transfusion and regression models to predict the number of blood product units to be ordered preoperatively. The study is reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist for prediction model development. Results The GBM performed best in both domains, with an area under receiver operating characteristic curve of 0.87 ± 0.03 (95% confidence interval) and F-score of 0.91 ± 0.04 for classification, and a mean squared error of 1.15 ± 0.12, R-squared (R) of 0.73 ± 0.02, and root mean squared error of 1.05 ± 0.06 for regression. GBM feature ranking determined that the following variables held the most information for prediction: platelet count, weight, preoperative hematocrit, surgical volume per institution, age, and preoperative hemoglobin. We then produced a calculator to show the number of units of blood that should be ordered preoperatively for an individual patient. Conclusions Anesthesiologists and surgeons can use this continually evolving predictive model to improve clinical care of patients presenting for craniosynostosis surgery.

BackgroundThe shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline POT1 mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic POT1 mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of POT1 mutations to development of other sporadic cancers is largely unexplored.MethodsWe performed logistic regression, adjusted for tumour mutational burden, to identify associations between POT1 mutation frequency and tumour type in 62 368 tumours undergoing next-generation sequencing.ResultsA total of 1834 tumours harboured a non-benign mutation of POT1 (2.94%), of which 128 harboured a mutation previously reported to confer familial cancer risk in the setting of germline POT1 deficiency. Angiosarcoma was 11 times more likely than other tumours to harbour a POT1 mutation (p=1.4×10−20), and 65% of POT1-mutated angiosarcoma had >1 mutations in POT1. Malignant gliomas were 1.7 times less likely to harbour a POT1 mutation (p=1.2×10−3) than other tumour types. Colorectal cancer was 1.2 times less likely to harbour a POT1 mutation (p=0.012), while melanoma showed no differences in POT1 mutation frequency versus other tumours (p=0.67).ConclusionsThese results confirm a role for shelterin dysfunction in angiosarcoma development but suggest that gliomas arising in the context of germline POT1 deficiency activate a telomere-lengthening mechanism that is uncommon in gliomagenesis.

PURPOSE: Voiding dysfunction (VD) leading to urinary retention is a common neurogenic lower urinary tract symptom in patients with multiple sclerosis (MS). Currently, the only effective management for patients with MS with VD is catheterization. Transcranial Rotating Permanent Magnet Stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions and the strength of their functional connections. In this pilot trial (ClinicalTrials.gov Identifier: NCT03574610), we investigated the safety and therapeutic effects of TRPMS in modulating brain regions of interest (ROIs) engaged with voiding initiation to improve VD in MS women. MATERIALS AND METHODS: Ten MS women with VD (having % post-void residual/bladder capacity [%PVR/BC] ≥40% or being in the lower 10th percentile of the Liverpool nomogram) underwent concurrent functional magnetic resonance imaging/urodynamic study (fMRI/UDS) with 3 cycles of bladder filling/emptying, at baseline and post-treatment. Predetermined ROIs and their activations at voiding initiation were identified on patients’ baseline fMRI/UDS scans, corresponding to microstimulator placement. Patients received 10 consecutive 40-minute treatment sessions. Brain activation group analysis, noninstrumented uroflow, and validated questionnaires were compared at baseline and post-treatment. RESULTS: No treatment-related adverse effects were reported. Post-treatment, patients showed significantly increased activation in regions known to be involved at voiding initiation in healthy subjects. %PVR/BC significantly decreased. Significant improvement of bladder emptying symptoms were reported by patients via validated questionnaires. CONCLUSIONS: Both neuroimaging and clinical data suggested TRPMS effectively and safely modulated brain regions that are involved in the voiding phase of the micturition cycle, leading to clinical improvements in bladder emptying in patients with MS.

Thalassemia is the most common congenital hemolytic disorder by a partial or complete deficiency in globin chain synthesis. Recent investigations have suggested a correlation between protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) deficiency and thrombosis. So, the aim of this study was to evaluate the PZ and ZPI levels in beta (β)-thalassemia patients. In this study, 40 patients with thalassemia major and 40 control subjects were selected. PZ and ZPI serum levels were measured by sandwich ELISA technique. PZ and ZPI were significantly higher in thalassemic patient group than control group. Also, PZ levels and PLT and Hb counts were significantly higher in splenectomized thalassemic patients than non-splenectomized ones. The exact mechanism of increased PZ and ZPI have an impact on hypercoagulable state in β-thalassemia major could not be found in our study. More studies are still needed to understand these challenges in β-thalassemia major patients.

Background There is a concern that the Oncology Care Model (OCM), a voluntary bundled payment program, may incentivize mergers and acquisitions among physician practices leading to reduced competition and price increases. These concerns are heightened if OCM is preferentially adopted in competitive health care markets because it could result in reduced competition, but little is known about the characteristics of markets where OCM is adopted. Objective To measure the association between regional market competition among medical oncologists with the initial adoption of OCM. Research design The Herfindahl-Hirschman Index (HHI), a measure of competition, was calculated for hospital referral regions (HRRs) using secondary data from the Centers for Medicare and Medicaid Services. The relationship between HHI and OCM adoption was assessed using a 2-part regression model adjusting for the market-level number of practices, physician density, average practice size, sociodemographic characteristics, and medical resources. A count model on all HRRs was also estimated to assess an overall effect. Subjects A total of 10,788 physicians in 3,537 practices who billed Medicare for oncology services in 2015. Results OCM was adopted in 114 (37%) of the 306 HRRs. We found that practices in competitive health care markets were more likely to adopt OCM than in noncompetitive markets. Two-part regression analysis indicated a nonlinear relationship between HHI and OCM adoption. Average practice size, number of practices in an HRR, and the hospital bed rate were positively associated with adoption, whereas the rate of full-time equivalent hospital employees to 1000 residents was negatively associated with adoption. Conclusions OCM adoption was higher in HRRs with greater competition. Careful monitoring of market-level changes among OCM adopters should be undertaken to ensure that the benefits of the OCM outweigh the negative consequences of possible changes in competition.

In this paper, the effectiveness of passive shielding of multiwalled carbon nanotube (MWCNT) bundle interconnects in reducing the crosstalk effects in carbon nanotube FET based ternary circuits is comprehensively investigated. In addition, based on the tighter sublithographic pitch of MWCNTs compared to Cu, we decrease the space between the carbon nanotube (CNT) interconnects to reduce the area overhead, while still having significantly higher effectiveness compared with Cu. The worst-case crosstalk delay and noise for passively shielded MWCNT and Cu wires at 14 nm technology are evaluated using comprehensive HSPICE simulations. The results indicate that the crosstalk delay and noise area in the efficient passively shielded MWCNT bundle interconnects are much smaller than the shielded Cu wires for ternary logic. Furthermore, the impacts of process variation on the crosstalk effects in these interconnects in ternary logic are investigated using Monte Carlo simulations. The results demonstrate the robustness of the passively shielded MWCNT bundles in ternary logic.

This study proposes a statistical approach to incident detection in a section of the intercity freeway by applying GPS probe data to a GIS geofenced platform. We evaluated the proposed method using data sources from real traffic sensors of the intercity Tehran-Qom freeway in Iran. Through the SEPEHTAN project in Iran, intercity bus fleet equipped with an onboard unit that provides GPS data transferring to the central database. The main novelties in this paper are gathering density and speed time series from GPS probe data in a GIS platform and using autocorrelation factor to detect the location of the incident. The method compared with three different AID algorithms and real terms as well. Although the penetration rate was 3%, the results were considerably meet with the actual traffic condition. We reached 92.8% detection rate and 7.1% for the false alarm.

To evaluate the efficacy of single low dose (75 mg) preoperative pregabalin in reducing post-operative pain of septorhinoplasty. A double blind single center Randomized controlled trial based on block randomization. In the pregabalin group (PG) 34 participants received 75 mg pregabalin orally one hour before anesthesia induction while in control group (CG) 34 participants received a placebo. Pain and sedation were repeatedly measured with Visual Analouge Scale (VAS) and Riker Sedation-Agitation Scale (RSAS) respectively, 0.5, 1, 2, 6, 24 hours postextubation. Cumulative doses of fentanyl and ibuprofen received in both groups were compared. Thirty-two of the participants in PG and 33 of the participants in CG completed the study. The Mean VAS pain score was less in PG versus CG 30 min postoperatively (2.30 ± 1.30 vs. 4.85 ± 1.17), one hour (2.28 ± 0.92 vs. 4.27 ± 0.78), two hours (2.11 ± 0.88 vs. 3.60 ± 0.61) and six hours (1.47 0.62 vs. 2.76 ± 0.91) but not 24-hours postoperatively (0.84 ± 0.62 vs. 1.09 ± 0.92). Participants in the PG were less agitated during early post-extubation period (at 10 min: RSAS 3.93 ± 0.43 vs. 4.42 ± 0.50) and more alert during the first hour post-extubation (at 60 min: RSAS 3.90 ± 0.29 vs. 3.36 ± 0.69). The total dose of rescue fentanyl and ibuprofen was lower in the PG compared to the CG. A single dose of 75 mg pregabalin is very effective for pain control after septorhinoplasty procedure when administered one hour before anesthesia induction. Side effects are rare and opioid sparing was noted. Clinical trial number: IRCT2017043033706N1

Background Discrepancies in controlled substance documentation are common and can lead to legal and regulatory repercussions. We introduced a visual analytics dashboard to assist in a quality improvement project to reduce the discrepancies in controlled substance documentation in the operating room (OR) of our free-standing pediatric hospital. Methods Visual analytics were applied to collected documentation discrepancy audit data and were used to track progress of the project, to motivate the OR team, and in analyzing where further improvements could be made. This was part of a seven-step improvement plan based on the Theory of Change with a logic model framework approach. Results The introduction of the visual analytics dashboard contributed a 24% improvement in controlled substance documentation discrepancy. The project overall reduced documentation errors by 71% over the studied period. Conclusion We used visual analytics to simultaneously analyze, monitor, and interpret vast amounts of data and present them in an appealing format. In conjunction with quality-improvement principles, this led to a significant improvement in controlled substance documentation discrepancies.

The low temperature absorption method is currently used in a gas-processing unit to control the natural gas dew point. The major problem of this unit is the simultaneous absorption of high amount o...

In this study, the reformate stabilizer tower of a petrochemical plant has been investigated for the first time. The main goal of this distillation tower is to separate light components and...

Introduction: Blood components are commonly used during surgical operations; however, limited sources are globally available in this regard. The present study aimed to assess blood product usage and wastage in Amir-Almomenin hospital, Zabol, Iran. Methods: A total of3883 ordered blood components were retrospectively analyzed in AmirAlmomenin hospital, Zabol, Iran (January) 2017-(July)2018. The data were analyzed using the SPSS software, version 18. Results: The results demonstrated that the most frequent ordered blood products included packed red blood cells (PRBCs, 2097 units, 54%), followed by fresh frozen plasma (823 units, 21.2%), platelet concentrates (757 units, 19.5%), and cryoprecipitate (206 units, 5.2%), respectively. Intensive care unit department had the highest records of orders (34.2%) and the ratio of crossmatched blood to transfused blood (C/T) was 1.73. In addition, based on the results, the total amount of component wastage was 2.03% with the highest and lowest percentage for PRBCs (59.6%) and cryoprecipitate (4.35%), respectively. The highest rate of wastage was related to the delivery ward (8.23%). There was no return from pediatrics, dialysis, pediatric critical care unit, critical care unit, and gastroenterology wards. Further, a significant difference was observed between the returned rates of D-positive and D-negative blood components with higher rates belonging to D-negative products (P=0.001). Conclusion: In general, due to the 2.03% wastage rate, there is an indispensable need regarding implementing sufficient supervision and assigning vigilant policies on the hospital-based transfusion policies in order to optimize the blood product management.

This study presents an efficient geometry for active shielding of multiwalled carbon nanotube (MWCNT) bundle interconnects which cancels the crosstalk-induced functional failures in ternary logic. In this geometry, MWCNT bundles are used innovatively as shields on both sides of the signal transmission line to reduce the crosstalk effects while maintaining the minimum interconnect pitch. Simulations are performed using HSPICE for intermediate and global interconnects in ternary logic at 14-nm node. The results indicate that the crosstalk-induced functional failure in ternary logic is omitted by using the proposed structure. Moreover, according to the results, our proposed geometry reduces the crosstalk noise peak as compared to the widened MWCNT bundles, distanced MWCNT bundles and Cu interconnects on average by 41%, 44%, and 61% for the intermediate interconnects and 61%, 46%, and 74% for the global interconnects, respectively, without any considerable power consumption penalties.

In this paper, the impacts of the simultaneous switching noise (SSN) in carbon nanotube field effect transistor-based ternary circuits are investigated. These effects, including the peak noise on the $V_{\mathrm {DD}}$ and ground rails and the SSN-induced delay and output noise are compared between traditional Cu and multiwall carbon nanotube bundle power interconnects in ternary circuits. Simulations are performed using HSPICE for global power interconnects at 14- and 7-nm technology nodes. The results indicate that for interconnects with 200- $\mu \text{m}$ length, the peak SSN voltage on the $V_{\mathrm {DD}}$ and ground rails for a power distribution network, including ten ternary buffers, using multi-walled carbon nanotube (MWCNT) bundle power interconnects is 53% and 40% lower, respectively, compared to Cu power interconnects in the last stage at the 14-nm node. Also, with scaling down the technology to 7 nm, these improvements increase to 60% and 59%, respectively. Moreover, MWCNT bundle power interconnects reduce the SSN-induced delay at the output of the tenth stage for interconnects with 200- $\mu \text{m}$ length on average by 82% as compared to the Cu interconnects at the 14-nm node. This improvement is 73% for the 7-nm technology node.

This research presents a numerical method to design a two-dimensional auxetic microstructure with negative Poisson’s ratios. The method is established by combining the finite element method (FEM) with two different optimization procedures called bi-directional evolutionary structural optimization (BESO) and solid isotropic material with penalization (SIMP), respectively. The results show that by choosing any of the two methods of optimization (FEM and BESO or FEM and SIMP), each with a different objective function, it is possible to create microstructures that show negative Poisson’s ratio. In addition, there is a significant resemblance between the results of both optimization methodologies. The final part of this study is to verify the outcome of optimization, both numerically and experimentally using three-dimensional (3D) printing techniques.

Background Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. Methods We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. Results We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). Conclusions IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.

Introduction The alloimmunization following blood transfusion can be life‐threatening. The Rh alloantibodies are one of the most common causes contributing to alloimmunization. This study aimed to evaluate the rate and causes of alloimmunization and to determine the Rh phenotypes and genotypes among sickle cell disease (SCD) and sickle thalassemia (Sβ). Materials and Methods Our study included 104 SCD and Sβ patients referring to Baghaei 2 Hospital of Ahvaz in 2019 using a non‐random simple sampling method. The blood samples were collected for Rh phenotypes, alloantibody screening and identification, and molecular tests. The SSP‐PCR and RFLP methods with the Pst 1 enzyme were used. Results The alloimmunization rate was 9.6% and 13.2% based on immunohematological tests and medical records, respectively. The main alloantibodies (90%) were anti‐Rh, and 40% of the patients had multiple alloantibodies. A significant correlation was found between gender and alloimmunization. The phenotypes of DCce (37.5%), DCcEe (24%), Dce (20.2%), and dce (5.8%) and genotypes of R1r (25%), R1R2 (20.2%), R1R1 (18.3%), and R1R0 (10.6%) were the most prevalent. The R1R2 was a frequent genotype in Sβ. Conclusion R0r′ and R1R0 genotypes were limited to our population in Iran. Due to the differences in RH genotypes between our population and others, the blood transfusion from other ethnicities increased our total alloimmunization rate., The alloimmunization is the problem in 9.6% of sickle cell disease (SCD) and sickle thalassemia patients.The increase in the rate of alloimmunization was due to Rh alloantibodies.The Rh genotypes were different among sickle cell disease and sickle thalassemia patients than other populations and R1r′ and R0R1 genotypes were limited to our population.

Paraneoplastic syndromes can commonly occur due to lung cancer, especially small cell lung cancer. Frequently paraneoplastic syndromes can precede the diagnosis of the neoplasm or present with limited stage disease. However, these syndromes can also occur at the time of recurrence or metastasis of disease. This review focuses on the epidemiology, pathogenesis, clinical features, and current management of the most common paraneoplastic syndromes encountered in patients with small cell lung cancer. Manifestations of paraneoplastic syndromes in small cell lung cancer include endocrine syndromes with secretion of excess hormones, and neurologic syndromes due to the production of antibodies causing an autoimmune condition. Recent advances have allowed for greater understanding of these syndromes and for the development of improved diagnostic as well as therapeutic tools. Awareness of paraneoplastic syndromes in small cell lung cancer can lead to an earlier diagnosis and recognition of both the condition and in some cases the disease potentially improving the overall survival and prognosis for patients. Further research examining effective methods to improve recovery from neurologic deficits in patients with a paraneoplastic neurologic illness is warranted.

OBJECTIVE Examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. BACKGROUND The risk of venous thromboembolism (VTE) is high for patients with gliomas (10–30%). Unfortunately, biomarkers and predictive models for development of a VTE in brain cancer have not been validated. Prior research has suggested that IDH wildtype gliomas are at higher risk for development of VTE compared to IDH mutant tumors. DESIGN/METHODS We conducted a retrospective chart review of glioma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC). We obtained demographics, date of tumor diagnosis, initial pathology, IDH status (mutated or wildtype), extent of initial resection, KPS at time of initial resection, history of VTE, development of VTE, type of VTE (PE/DVT), KPS at time of VTE, treatment for VTE, bleeding complications, glioma treatments, date of last follow up and/or death. RESULTS We identified 282 astrocytoma patients consisting of 49 IDH mutant and 233 IDH wildtype astrocytomas. Glioblastoma was the histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45 (19.3%) of the IDH wild type astrocytomas (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p =0.8663). CONCLUSIONS IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.

Introduction: Hypertonic saline (HS) has an important role in the treatment of raised intracranial pressure after traumatic brain injury. This study evaluates the efficacy and safety of HS and its impact on the postoperative course of patients undergoing craniotomy for low-grade gliomas. Materials and Methods: Sixty patients with supratentorial low-grade glioma were enrolled. All patients were anesthetized and operated with the same team and protocol. They successively received either HS or mannitol just before surgery. The amount of brain edema was classified according to the dural tension score (I–III) just after craniotomy and before dural opening. Other intraoperative measurements (such as urine output, need, and dosage of other diuretic agents) and postoperative findings (intensive care unit [ICU] and hospital stay, corticosteroid demand, and confusion period) were also assessed. Pre- and postoperative serum S100B levels were documented in both groups. Results: The dural tension score was not significantly different among the two groups: severe tension in six and five patients in the mannitol and HS groups, respectively. HS group had a significantly lower amount of diuresis (609 vs. 725 ml) during surgery. Patients in the HS group had shorter ICU stay (16.3 vs. 27.9 h) and shorter duration of corticosteroid therapy after surgery (3.4 vs. 5.2 days). Conclusion: HS infusion just before the onset of craniotomy is at least as effective as mannitol in controlling intraoperative brain edema in patients with supratentorial glioma. Improved early postoperative course and lower degrees of S100B rise after craniotomy seen in the HS group needs to be explained in more detailed studies.

Background Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. Methods This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative “value” of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. Discussion Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

ObjectivesConferences are designed for knowledge translation, but traditional conference evaluations are inadequate. We lack studies that explore alternative metrics to traditional evaluation metrics. We sought to determine how traditional evaluation metrics and Twitter metrics performed using data from a conference of the Canadian Association of Emergency Physicians (CAEP).MethodsThis study used a retrospective design to compare social media posts and tradition evaluations related to an annual specialty conference. A post (“tweet”) on the social media platform Twitter was included if it associated with a session. We differentiated original and discussion tweets from retweets. We weighted the numbers of tweets and retweets to comprise a novel Twitter Discussion Index. We extracted the speaker score from the conference evaluation. We performed descriptive statistics and correlation analyses.ResultsOf a total of 3,804 tweets, 2,218 (58.3%) were session-specific. Forty-eight percent (48%) of all sessions received tweets (mean = 11.7 tweets; 95% CI of 0 to 57.5; range, 0–401), with a median Twitter Discussion Index score of 8 (interquartile range, 0 to 27). In the 111 standard presentations, 85 had traditional evaluation metrics and 71 received tweets (p > 0.05), while 57 received both. Twenty (20 of 71; 28%) moderated posters and 44% (40 of 92) posters or oral abstracts received tweets without traditional evaluation metrics. We found no significant correlation between Twitter Discussion Index and traditional evaluation metrics (R = 0.087).ConclusionsWe found no correlation between traditional evaluation metrics and Twitter metrics. However, in many sessions with and without traditional evaluation metrics, audience created real-time tweets to disseminate knowledge. Future conference organizers could use Twitter metrics as a complement to traditional evaluation metrics to evaluate knowledge translation and dissemination.

When receiving machine learning services from the cloud, the provider does not need to receive all features; in fact, only a subset of the features are necessary for the target prediction task. Discerning this subset is the key problem of this work. We formulate this problem as a gradient-based perturbation maximization method that discovers this subset in the input feature space with respect to the functionality of the prediction model used by the provider. After identifying the subset, our framework, Cloak, suppresses the rest of the features using utility-preserving constant values that are discovered through a separate gradient-based optimization process. We show that Cloak does not necessarily require collaboration from the service provider beyond its normal service, and can be applied in scenarios where we only have black-box access to the service provider's model. We theoretically guarantee that Cloak's optimizations reduce the upper bound of the Mutual Information (MI) between the data and the sifted representations that are sent out. Experimental results show that Cloak reduces the mutual information between the input and the sifted representations by 85.01% with only a negligible reduction in utility (1.42%). In addition, we show that Cloak greatly diminishes adversaries' ability to learn and infer non-conducive features., This paper is presented at the 2021 Web conference (WWW 2021)

Objective Triplicate A2 segment of the anterior cerebral artery is a rare anatomical variant (1%–3% prevalence) that which is thought to result mainly from persistence of the embryonic median artery of the corpus callosum. We sought to determine whether the triple-A2 variant is specifically associated with anterior communicating artery (ACoA) aneurysm. Methods We reviewed 2-dimensional digital-subtraction angiography (2D-DSA) as well as 3-dimensional rotational angiography (3D-RA) images of 55 patients with ACoA aneurysms who presented for evaluation and treatment between 2009 and 2014 at our institution. The criteria for definitively obtaining an accurate accounting of all A2 segments was presence of adequate cross-filling across the ACoA on 2D-DSA or 3D-RA imaging, or ability to fuse left and right 3D-RA images. Patients whose imaging did not meet these criteria were excluded from further analysis. Results We obtained a definitive count of all A2 segments in 36 patients. Among these, 19 patients (5 with the triple-A2 variant) were treated surgically, and 17 patients (2 with the triple-A2 variant) were treated endovascularly. The triple-A2 variant was seen in 7 patients. The prevalence of triple-A2 variant among patients with ACoA aneurysm was 19.4%. Patients with ACoA aneurysms had a significantly higher prevalence of the triple-A2 variant compared with the general population (P Conclusions Compared with the normal population, patients with ACoA aneurysms deemed to require treatment have a significantly higher likelihood of having triplicate A2 segment. Knowledge of this anatomical variation is of critical importance in planning and executing endovascular and microsurgical treatment of ACoA aneurysms.

A wide variety of deep neural applications increasingly rely on the cloud to perform their compute-heavy inference. This common practice requires sending private and privileged data over the network to remote servers, exposing it to the service provider and potentially compromising its privacy. Even if the provider is trusted, the data can still be vulnerable over communication channels or via side-channel attacks in the cloud. To that end, this paper aims to reduce the information content of the communicated data with as little as possible compromise on the inference accuracy by making the sent data noisy. An undisciplined addition of noise can significantly reduce the accuracy of inference, rendering the service unusable. To address this challenge, this paper devises Shredder, an end-to-end framework, that, without altering the topology or the weights of a pre-trained network, learns additive noise distributions that significantly reduce the information content of communicated data while maintaining the inference accuracy. The key idea is finding the additive noise distributions by casting it as a disjoint offline learning process with a loss function that strikes a balance between accuracy and information degradation. The loss function also exposes a knob for a disciplined and controlled asymmetric trade-off between privacy and accuracy. While keeping the DNN intact, Shredder divides inference between the cloud and the edge device, striking a balance between computation and communication. In the separate phase of inference, the edge device takes samples from the Laplace distributions that were collected during the proposed offline learning phase and populates a noise tensor with these sampled elements. Then, the edge device merely adds this populated noise tensor to the intermediate results to be sent to the cloud. As such, Shredder enables accurate inference on noisy intermediate data without the need to update the model or the cloud, or any training process during inference. We also formally show that Shredder maximizes privacy with minimal impact on DNN accuracy while the tradeoff between privacy and accuracy is controlled through a mathematical knob. Experimentation with six real-world DNNs from text processing and image classification shows that Shredder reduces the mutual information between the input and the communicated data to the cloud by 74.70% compared to the original execution while only sacrificing 1.58% loss in accuracy. On average, Shredder also offers a speedup of 1.79x over Wi-Fi and 2.17x over LTE compared to cloud-only execution when using an off-the-shelf mobile GPU (Tegra X2) on the edge.

Objective To evaluate the cost-effectiveness of nusinersen with and without universal newborn screening for infantile-onset spinal muscular atrophy (SMA). Study design A Markov model using data from clinical trials with US epidemiologic and cost data was developed. The primary interventions studied were nusinersen treatment in a screening setting, nusinersen treatment in a nonscreening setting, and standard care. Analysis was conducted from a societal perspective. Results Compared with no screening and no treatment, the incremental cost-effectiveness ratio (ICER) for nusinersen with screening was $330 558 per event-free life year (LY) saved, whereas the ICER for nusinersen treatment without screening was $508 481 per event-free LY saved. For nusinersen with screening to be cost-effective at a willingness-to-pay (WTP) threshold of $50 000 per event-free LY saved, the price would need to be $23 361 per dose, less than one-fifth its current price of $125 000. Preliminary data from the NURTURE trial indicated an 85.7% improvement in expected LYs saved compared with our base results. In probabilistic sensitivity analysis, nusinersen and screening was a preferred strategy 93% of the time at a $500 000 WTP threshold. Conclusion Universal newborn screening for SMA provides improved economic value for payers and patients when nusinersen is available.

Improving access to surgical services and understanding the barriers to receiving timely care are necessary to save lives. The aim of this study was to assess barriers to timely presentation to an appropriate medical facility using the Three-Delay model, for patients presenting to Tamale Teaching Hospital, in northern Ghana. In 2013, patients with delays in seeking surgical care were prospectively identified. Pairwise correlation coefficients between delay in presentation and factors associated with delay were conducted and served as a foundation for a multivariate log-linear regression model. A total of 718 patients presented with an average delay of 22.1 months. Delays in receiving care were most common (56.4%), while delays in seeking care were seen in 52.3% of patients. “Initially seeking treatment at the nearest facility, but appropriate care was unavailable” was reported by 56.4% and predicted longer delays (p

Process optimization of CO2 removal from natural gas by a polyvinylidene fluoride hollow-fiber membrane contactor is a major goal of many computational fluid dynamics (CFD) simulations in this area...

Study Design:Retrospective review.Objective:To determine whether abnormal preoperative testing is associated with postoperative complications in patients undergoing a microdiscectomy.Methods:Patients undergoing a microdiscectomy between 2006 and 2013 were identified in the National Surgical Quality Improvement Program database based on appropriate current procedural terminology coding. Thirty-day postoperative complications were analyzed in addition to patient demographics, comorbidities, and abnormal preoperative laboratory values. A series of over 650 univariate analyses to determine which independent variables to include for each complication were completed. Based on those analyses, 12 logistic regression models were built, one for each specific complication. Each model adjusted for age, gender, comorbidities, American Society of Anesthesiologists classification, as well as operative time.Results:A total of 5947 patients undergoing a microdiscectomy were included in the study. Abnormal preoperative international normalized ratio (odds ratio [OR] = 5.85, P < .05) was associated with any wound infection, superficial or deep, and abnormal partial thromboplastin time was significantly associated with wound dehiscence (OR = 6.80, P < .05). Postoperative urinary tract infections were associated with abnormal preoperative hematocrit (OR = 8.00, P < .05). None of the identified preoperative labs were independently associated with pulmonary embolism, organ space surgical site infections, or intubation.Conclusions:Abnormal preoperative coagulation labs were significantly associated with postoperative wound complications. However, the majority of tests were not associated with adverse events following microdiscectomy. Further study is necessary to conclude whether these tests provide information that can modify perioperative management and whether widespread testing is cost-effective.

Multiple-valued logic systems have been considered as a solution for the challenges of the nanoscale binary very large scale integration chips. However, the main concerns about these systems are the noise impacts, especially in the presence of process and temperature variations. In this study, the impacts of process and temperature variations on the crosstalk effects in multiwall carbon nanotube (MWCNT) bundle interconnects in ternary systems are investigated. The deviation in the worst-case crosstalk delay, noise, and the power introduced by the process variations are investigated using comprehensive Monte Carlo simulations. Also, analyses are conducted for the global level interconnects at 22 nm technology node for repeated MWCNT bundle interconnects. The results indicate that the average deviations in the worst-case crosstalk delay and crosstalk noise area in the presence of all sources of process variations in the repeated MWCNT bundle interconnects are about 14%. In addition, the maximum variations in the lumped resistance, distributed resistance, kinetic inductance, electrostatic capacitance, coupling capacitance and quantum capacitance of the MWCNT bundle interconnects in ternary systems in the presence of all sources of process variations are 4.6%, 14%, 7.2%, 8.2%, 5.1%, and 5.6%, respectively. According to the results, higher temperature increases the resistance of the MWCNT bundle interconnects and thereby the crosstalk delay and crosstalk noise area mainly due to the reduction of the mean free path of the MWCNTs in a bundle.

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.

Modified atmosphere and humidity packaging (MAHP) is used to extend shelf life and maintaining the quality of fresh fruits and vegetables by modifying desired gas concentration and relative humidity (RH) inside fresh produce package. Several factors affect the optimum design of MAHP, most of which are time and or temperature dependent. Hence, there is a vital need for a simulation tool that includes all affecting parameters and their interactive behavior on package gas composition and water vapour. In this study a comprehensive simulation program based on integrative mathematical modeling is presented. A number of validation experiments were conducted to evaluate the robustness of the simulation program under constant and varying temperature conditions during storage period and predict gas composition, humidity and moisture condensation dynamics in packaged strawberry and plum. The simulated results were satisfactory with those obtained experimentally. The validated simulation program was then used for optimization of modified humidity packaging for both plum and strawberry. The predicted equilibrium headspace humidity was 94.0 and 98.8% for strawberries and plums, respectively which was very close to measured values of 93.5 and 94.1%, respectively. Therefore, the simulation program was found to be a convenient tool to virtually test the package under a broad range of environmental conditions such as temperature and RH resembling real supply chain conditions and ensure proper selection of packaging systems for the optimum performance.

Based on a feedback system, an N-path bandpass filter robust to even-order harmonic mixing (BPF-REHM) is presented. BPF-REHM consists of a conventional differential N-path filter around a gain stage. Despite assuming a single-ended antenna, this work aims at partial rejection of even-order harmonics before the signal travels through the baseband circuitry. Linear periodically time-varying analysis of the new filter is presented. Mathematical derivations verify an enhanced-Q filtering behavior in addition to even-order harmonic rejection at RF nodes. Drawback of BPF-REHM, i.e., input impedance mismatch, is addressed by proposing a two-stage LNA. The second stage of the new LNA, which is the BPF-REHM, suppresses even-order harmonic blockers while the first stage matches the input to the source and provides enough gain to accomplish an acceptable overall noise performance. The design example is a 500?MHz four-path filter simulated with the 90?nm CMOS. It achieves >22?dB even harmonic rejection with an enhanced-Q filtering characteristic thanks to the new technique. Besides, this design achieves 21?dB gain, 2?dB NF, and $$+$$+2.5?dBm out-of-band IIP3 at 50?MHz offset while consuming 8.3?mW of power.

Background Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms “‘gastrointestinal stromal tumor’ AND brain AND metastasis”” was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. Case presentation A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). Conclusions Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

BACKGROUND Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in clinical trials (including EORTC 22981) as well as their historically-poor overall survival. METHODS Retrospective chart review was conducted at a single high-volume cancer center for newly-diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS A total of 158 newly-diagnosed GBM patients aged 65 years and older were identified. 144 patients (91.1%) underwent radiation therapy. One-hundred thirty patient (90.3%) received concurrent temozolomide with radiotherapy. A minority of patients (23%) discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temodar. The median overall survival (OS) time for our cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p=0.002, HR 0.46; 95% CI: 0.63–0.82), completing planned course of radiation (p=0.01, HR 0.29; 95% CI: 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p=0.01, HR 2.62; 95% CI: 1.67–4.12) were associated with improved OS. CONCLUSIONS Our cohort of elderly GBM patients were predominately treated with a standard of care based on EORTC 22981. Despite their age, these patients tolerated treatment well and had a favorable overall survival compared to outcomes reported for patients treated on EORTC 22981. Using age alone as the reason to de-escalate treatment or as an exclusionary criteria in clinical trials should be discouraged.

Economic evaluations provide evidence that informs stakeholders on how to efficiently allocate real and financial healthcare resources. The purpose of this study was to review and discuss the integration of economic evaluations into the National Drug Abuse Treatment Clinical Trials Network (CTN) since its inception, as well as expectations for the future of this relationship. A systematic review was performed on published and planned CTN economic evaluations in the CTN dissemination library and PubMed. The well-established Drummond checklist was used to evaluate the comprehensiveness and methodological rigor of published articles. One hundred thirty-eight ancillary, follow-up, or original protocols were reviewed, and 78 potentially relevant published articles were identified. A total number of 14 protocols included an economic evaluation. Of these, 6 protocols were completed, 2 were reported as active, and 6 were reported as in-development at the time of this review. Of the 78 published articles, 9 met the inclusion criteria. As gauged by the Drummond checklist, the quality of CTN published economic evaluations were found to improve over time, and recent published articles were identified as guides to cutting-edge economic research. As the CTN continues to grow and mature, it is imperative that high-quality economic evaluations are incorporated alongside trials in order to maximize the public health impact of the CTN.

The Norwood surgical procedure restores functional systemic circulation in neonatal patients with single ventricle congenital heart defects, but this complex procedure carries a high mortality rate. In this study we address the need to provide an accurate patient specific risk prediction for one-year postoperative mortality or cardiac transplantation and prolonged length of hospital stay with the purpose of assisting clinicians and patients’ families in the preoperative decision making process. Currently available risk prediction models either do not provide patient specific risk factors or only predict in-hospital mortality rates. We apply machine learning models to predict and calculate individual patient risk for mortality and prolonged length of stay using the Pediatric Heart Network Single Ventricle Reconstruction trial dataset. We applied a Markov Chain Monte-Carlo simulation method to impute missing data and then fed the selected variables to multiple machine learning models. The individual risk of mortality or cardiac transplantation calculation produced by our deep neural network model demonstrated 89 ± 4% accuracy and 0.95 ± 0.02 area under the receiver operating characteristic curve (AUROC). The C-statistics results for prediction of prolonged length of stay were 85 ± 3% accuracy and AUROC 0.94 ± 0.04. These predictive models and calculator may help to inform clinical and organizational decision making.

Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63–0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67–4.12) were independently associated with improved OS. Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Informed consent is fundamental to the ethical practice of medicine and carries important legal implications. Of particular relevance to pediatric anesthesia is the Food and Drug Administration's Drug Safety Communication (DSC), which highlights potential yet theoretical adverse effects on brain development of repeated or prolonged anesthesia administration to children younger than 3 years of age.

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy., Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis.