Utilization of palliative care resource remains low, consuming potentially avoidable hospital admissions in stage IV non-small cell lung cancer: a community-based retrospective review.

PURPOSE: Early referral of patients with stage IV non-small cell lung cancer (NSCLC) to outpatient palliative care has been shown to increase survival and reduce unnecessary healthcare resource utilization. We aimed to determine outpatient palliative care referral rate and subsequent resource utilization in patients with stage IV NSCLC in a multistate, community-based hospital network and identify rates and reasons for admissions within a local healthcare system of Washington State. METHODS: A retrospective chart review of a multistate hospital network and a local healthcare system. Patients were identified using ICD billing codes. In the multistate network, 2844 patients diagnosed with stage IV NSCLC between January 1, 2013, and March 1, 2018, were reviewed. In the state healthcare system, 283 patients between August 2014 and June 2017 were reviewed. RESULTS: Referral for outpatient palliative care was low: 8% (217/2844) in the multistate network and 11% (32/283) in the local healthcare system. Early outpatient palliative care (6%, 10/156) was associated with a lower proportion of patients admitted into the intensive care unit in the last 30 days of life compared to no outpatient palliative care (15%, 399/2627; p = 0.003). Outpatient palliative care referral was associated with improved overall survival in Kaplan Meier survival analysis. Within the local system, 51% (104/204) of admissions could have been managed in outpatient setting, and of the patients admitted in the last 30 days of life, 59% (87/147) experienced in-hospital deaths. CONCLUSION: We identified underutilization of outpatient palliative care services within stage IV NSCLC patients. Many patients with NSCLC experience hospitalization the last month of life and in-hospital death.

Cardiovascular procedural deferral and outcomes over COVID-19 pandemic phases: A multi-center study.

BACKGROUND: The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations. METHODS: Cardiovascular procedures performed at 30 hospitals across 6 Western states in 2 large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression. RESULTS: Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in 2 distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15-April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (P = .0003), older (P < .0001), Asian or Black (P = .02), or Medicare insured (P < .0001), and COVID I procedures were higher acuity (P < .0001), but not higher complexity. In COVID II, there was a trend toward more procedural deferral in regions with a higher COVID-19 burden (P = .05). Compared to pre-COVID, there were no differences in risk-adjusted in-hospital mortality during both COVID phases. CONCLUSIONS: Significant decreases in cardiovascular procedural volumes occurred early in the COVID-19 pandemic, with disproportionate impacts by race, gender, and age. These findings should inform our approach to future healthcare disruptions.

The Diagnostic Yield of Repeated Endoscopic Evaluation in Patients with Gastrointestinal Bleeding and Left Ventricular Assist Devices.

INTRODUCTION: Left ventricular assist devices (LVADs) are increasingly common in patients with advanced heart failure. GI bleeding (GIB) occurs in 20-30 % of these patients and can arise anywhere in the GI tract. Given the high rates of GIB in this population, our aim was to determine the diagnostic yield of repeated endoscopic evaluation in these patients. METHODS: We performed a retrospective review of all 257 patients who had LVADs placed between 2008 and 2013 at Duke University Hospital and identified all patients who underwent any endoscopic evaluation for GIB. RESULTS: Of the 257 patients with LVADs placed, 78 (30 %) underwent at least one endoscopy for GIB. A source was identified in 36 % of cases, most commonly angioectasias (53.6 %). Treatment was performed in 67.9 % of patients and hemostasis was achieved in all. 64.1 % of the cohort underwent a second endoscopy for GIB. 42.9 % of these exams revealed a bleeding source. Endoscopic treatment was employed in 76.2 %. 38.5 % of the cohort underwent a third endoscopic exam for bleeding and a source was identified in 53.3 % with angioectasias remaining most common (56.3 %). By Fisher's exact and Chi-square testing, only the presence of a bleeding source (p = 0.0034) and use of hemostatic therapy (p = 0.0127) on the index examination were significantly associated with re-bleeding. CONCLUSIONS: GIB is common in patients with LVADs. The diagnostic and therapeutic yield of endoscopy is remains high with repeated interventions. Despite these high yields, a large portion of the cohort requires repeated interventions for recurrent bleeding.

Applications of the bayesian prior information to evaluation of equivalence of similar biological medicinal products.

In 2014, there are a number of patents of best-selling biotech drugs around the world about to expire. Large commercial interests will inevitably set off international competition among major pharmaceutical companies. The European Union, the United States, and other countries with advanced medical techniques have paid a high degree of attention to biological similarity (biosimilarity) for drug development and market management and have started to take corresponding measures. Because of the diverse definitions of biosimilarity between countries, which can determine whether the medicines on sale are in the review of the base grant, the competent authority will also encounter varying degrees of standards. Governments should review the corresponding guidelines as soon as possible because many countries around the world have actively amended the law in response to management need of biological similarity. The similarity of biological drugs should be assessed by clinical trial under current regulations. Pharmaceutical companies try to lower the cost of generic drugs to increase the competitiveness of their products. To reduce the number of subjects in the clinical trials for development of generic drugs, we refer to the clinical trial for evaluation of bridging studies. Hsiao et al. (2007) has proposed the use of Bayes method in evaluation of bridging studies. Prior information on the original region is used to reduce the number of subjects to lower the cost of biosimilar drug development. Take the results of the approval biologics as a priori information, and the information is appropriate to be embedded into the model evaluating the similar products in order to reduce the sample size required for the assessment of the test sample.

Safety and Outcomes of Outpatient Pleural Drainage in Symptomatic Postoperative Cardiac Surgery Patients.

BACKGROUND: Symptomatic pleural effusions and anticoagulant/antiplatelet medication use in postoperative cardiac surgery are common. Guidelines and recommendations are currently mixed regarding medication management related to invasive procedure performance. We aimed to describe the outcomes of postoperative cardiac surgery patients referred for outpatient, symptomatic pleural effusion management. METHODS: A retrospective study of post-cardiac surgery patients undergoing outpatient thoracentesis from 2016 to 2021 was performed. Demographics, operative details, pleural disease characteristics, outcomes, and complications were collected. Odds ratios with confidence intervals were estimated and adjusted by multivariate logistic regression to investigate the association with multiple thoracenteses. RESULTS: A total of 110 patients underwent 332 thoracenteses. The median age was 68 years and most common operation was coronary artery bypass. Anticoagulation or antiplatelet use was identified in 97%. Thirteen complications were identified, with all major complications (n=3) related to bleeding. The amount of fluid present at the time of initial thoracentesis (>1500 milliliters) was associated with increased odds ratio of subsequent multiple thoracentesis (Unadjusted odds ratio, 6.75 (CI - 1.43 to 31.9). No other variables had a significant association with the need for multiple procedures. CONCLUSION: Within a postoperative cardiac surgery population presenting with symptomatic pleural disease, we observed that thoracentesis performed on antiplatelet and/or anticoagulant medication is relatively safe. We also identified that many patients can be managed as outpatients and that most pleural effusions remain self-limited. The presence of larger amounts of pleural fluid at initial thoracentesis may be associated with increased odds for additional drainage.

Sepsis Order Set Use Associated with Increased Care Value.

BACKGROUND: Sepsis is common and expensive and there is evidence that sepsis order sets may help improve care. There is very incomplete evidence of the effects of sepsis order sets on the value of care produced by hospitals or the societal costs of sepsis care. RESEARCH QUESTION: In patients hospitalized for sepsis, is the receipt a of a sepsis order set vs. no order set associated with improved value of care, defined as decreased hospital mortality, decreased hospital direct variable costs and decreased societal spending on hospitalizations? STUDY DESIGN AND METHODS: Retrospective cohort study of patients discharged with sepsis ICD-10 codes over two years from a large integrated delivery system. Using a propensity score, sepsis order set users were matched to non-users to study the association between sepsis order set use and the value of care from the hospital and societal perspective. The association between order set receipt and hospital mortality, direct variable cost, and hospital revenue were also examined in a priori defined subgroups of sepsis severity and hospital mortality. RESULTS: 97,249 patients were included in the study with 52,793 (54%) receiving the sepsis order set. 55,542 patients were included in the propensity score match analysis, 27,771 in each group. Recipients of the sepsis order set had a 3.3% lower hospital mortality rate, a $1487 lower median direct variable total cost (P < 0.01 for both). Median payer neutral reimbursement (PNR), a proxy for hospital revenue and thus societal costs, was $465 lower for sepsis order set users (P < 0.01). Receipt of the sepsis order set was associated with an $1022 increase in contribution margin, the difference between direct variable costs and PNR per patient. INTERPRETATION: Receipt of the sepsis order set was associated with improved value of care, from both a hospital and societal perspective.

Statistical methods for assessing interchangeability of biosimilars.

Unlike traditional small molecule (chemical) drug products, the development of biologic products is very different and variable with respect to the manufacturing process and environmental factors such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make quantitative evaluation of follow-on biologics a great challenge to both scientific community and regulatory agencies. In this article, we propose a general approach for development of a biosimilarity index based on the concept of reproducibility probability for quantitative evaluation of biosimilarity and interchangeability. The proposed method is robust regardless the biosimilarity criteria used and/or study design employed.

Bone Cement Waste in Total Knee Arthroplasty: A Preliminary Study of Scope and Cost.

Background: Medical waste is both costly and detrimental to the environment, and operating room waste represents a substantial portion of this. To the authors' knowledge, bone cement waste in total knee arthroplasty (TKA) has not previously been studied. The vast majority of TKA are cemented, and the volume of TKA is forecast to increase. Given this, we studied the waste resulting from the routine use of 2 40-gram bags of polymethyl methacrylate (PMMA) powder during cementing in primary TKA. Methods: We first studied the yield of commercially available plain and gentamicin medium-viscosity bone cement powder and calculated the cost/gram of product. We then collected the PMMA remaining after primary TKA to determine the average amount of waste, its cost, and possible correlations with patient and implant metrics that could improve efficiency and reduce waste of PMMA. Results: Overall, PMMA waste averaged 59% per TKA, at a median cost of $129 per case. Cost of waste was greater when gentamicin cement was used, as its cost was 2.5X that of plain cement. Implant sizes and surface area ranges were identified that could reliably allow the use of a single 40-gram package of powder, potentially reducing PMMA waste. Conclusions: While it is acknowledged that zero-waste cementing is not practical, any reduction in waste that does not compromise either the flow of surgery or the adequacy of fixation would be beneficial. Reevaluation of PMMA techniques could reduce waste, resulting in both cost savings and improved sustainability in arthroplasty.

Characterization of Individuals With Apparent Resistant Hypertension Using Contemporary Guidelines: Insights From CV-QUIC.

BACKGROUND: Apparent resistant hypertension (aRH) carries excess cardiovascular risk beyond nonresistant forms of hypertension; however, our understanding of this at-risk population, as defined by current US practice guidelines, is limited. Accordingly, we sought to evaluate the prevalence, clinical characteristics, and pharmacotherapeutic patterns of patients with aRH using contemporary blood pressure guidance. METHODS: We classified patients at 3 large healthcare systems by hypertensive status using contemporary hypertension guidelines. We subsequently described the demographic and clinical characteristics of patients with aRH and compared these factors among hypertensive patients without aRH and between those with controlled and uncontrolled aRH. RESULTS: A total of 2 420 468 patients were analyzed, of whom 1 343 489 (55.6%) were hypertensive according to contemporary guidelines. Among hypertensive patients, 11 992 (8.5%) met criteria for aRH, with nearly all assessed comorbid conditions, particularly diabetes and heart failure, being more common in those with aRH. When compared with patients with uncontrolled aRH, those with controlled aRH were more frequently prescribed a beta-blocker, diuretic, and nitrate, with the largest standardized difference observed for a mineralocorticoid receptor antagonist (35.4% versus 10.4%, Cohen D 0.62). Consistent findings were noted in sensitivity analyses using the blood pressure threshold of 140/90 mm Hg. CONCLUSIONS: In an analysis of over 2.4 million individuals, a lower prevalence of aRH was observed than previously reported (12%-15%), but with a high burden of comorbidities. Identification of differences in pharmacotherapy between patients with controlled and uncontrolled aRH, particularly lower rates of mineralocorticoid receptor antagonist use, help define potential opportunities to improve care and lower cardiovascular risk.

Comparable Outcomes for Transcarotid and Transfemoral Transcatheter Aortic Valve Replacement at a High Volume US Center.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.

Excess Mortality Among Patients Hospitalized During the COVID-19 Pandemic.

BACKGROUND: The extent to which the COVID-19 pandemic has affected outcomes for patients with unplanned hospitalizations is unclear. OBJECTIVE: To examine changes in in-hospital mortality for patients without COVID-19 during the first 10 months of the pandemic (March 4, 2020 to December 31, 2020). DESIGN, SETTING, AND PARTICIPANTS: Observational study of adults with unplanned hospitalizations at 51 hospitals across 6 Western states. EXPOSURES: Unplanned hospitalizations occurring during the spring COVID-19 surge (March 4 to May 13, 2020; Period 1), an intervening period (May 14 to October 19, 2020; Period 2), and the fall COVID-19 surge (October 20 to December 31, 2020; Period 3) were compared with a pre-COVID-19 baseline period from January 1, 2019, to March 3, 2020. MAIN OUTCOMES AND MEASURES: We examined daily hospital admissions and in-hospital mortality overall and in 30 conditions. RESULTS: Unplanned hospitalizations declined steeply during Periods 1 and 3 (by 47.5% and 25% compared with baseline, respectively). Although volumes declined, adjusted in-hospital mortality rose from 2.9% in the pre-pandemic period to 3.5% in Period 1 (20.7% relative increase), returning to baseline in Period 2, and rose again to 3.4% in Period 3. Elevated mortality was seen for nearly all conditions studied during the pandemic surge periods. CONCLUSION: Pandemic COVID-19 surges were associated with higher rates of in-hospital mortality among patients without COVID-19, suggesting disruptions in care patterns for patients with many common acute and chronic illnesses.

Prostate Health Index Density Outperforms Prostate Health Index in Clinically Significant Prostate Cancer Detection.

BACKGROUND: Prostate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease. METHODS: A total of 412 men with PSA of 2-20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound. RESULTS: Of the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15-1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p=0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting. CONCLUSION: The PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa.

Case Rates, Treatment Approaches, and Outcomes in Acute Myocardial Infarction During the Coronavirus Disease 2019 Pandemic.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has changed health care delivery worldwide. Although decreases in hospitalization for acute myocardial infarction (AMI) have been reported during the pandemic, the implication for in-hospital outcomes is not well understood. Objective: To define changes in AMI case rates, patient demographics, cardiovascular comorbidities, treatment approaches, and in-hospital outcomes during the pandemic. Design, Setting, and Participants: This cross-sectional study retrospectively analyzed AMI hospitalizations that occurred between December 30, 2018, and May 16, 2020, in 1 of the 49 hospitals in the Providence St Joseph Health system located in 6 states (Alaska, Washington, Montana, Oregon, California, and Texas). The cohort included patients aged 18 years or older who had a principal discharge diagnosis of AMI (ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI]). Segmented regression analysis was performed to assess changes in weekly case volumes. Cases were grouped into 1 of 3 periods: before COVID-19 (December 30, 2018, to February 22, 2020), early COVID-19 (February 23, 2020, to March 28, 2020), and later COVID-19 (March 29, 2020, to May 16, 2020). In-hospital mortality was risk-adjusted using an observed to expected (O/E) ratio and covariate-adjusted multivariable model. Exposure: Date of hospitalization. Main Outcomes and Measures: The primary outcome was the weekly rate of AMI (STEMI or NSTEMI) hospitalizations. The secondary outcomes were patient characteristics, treatment approaches, and in-hospital outcomes of this patient population. Results: The cohort included 15 244 AMI hospitalizations (of which 4955 were for STEMI [33%] and 10 289 for NSTEMI [67%]) involving 14 724 patients (mean [SD] age of 68 [13] years and 10 019 men [66%]). Beginning February 23, 2020, AMI-associated hospitalizations decreased at a rate of -19.0 (95% CI, -29.0 to -9.0) cases per week for 5 weeks (early COVID-19 period). Thereafter, AMI-associated hospitalizations increased at a rate of +10.5 (95% CI, +4.6 to +16.5) cases per week (later COVID-19 period). No appreciable differences in patient demographics, cardiovascular comorbidities, and treatment approaches were observed across periods. The O/E mortality ratio for AMI increased during the early period (1.27; 95% CI, 1.07-1.48), which was disproportionately associated with patients with STEMI (1.96; 95% CI, 1.22-2.70). Although the O/E mortality ratio for AMI was not statistically different during the later period (1.23; 95% CI, 0.98-1.47), increases in the O/E mortality ratio were noted for patients with STEMI (2.40; 95% CI, 1.65-3.16) and after risk adjustment (odds ratio, 1.52; 95% CI, 1.02-2.26). Conclusions and Relevance: This cross-sectional study found important changes in AMI hospitalization rates and worse outcomes during the early and later COVID-19 periods. Future studies are needed to identify contributors to the increased mortality rate among patients with STEMI.

Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma.

BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS: Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS: Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION: A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients.

OBJECTIVES: Aortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions. METHODS: Using a patient-level simulation model, the potential cost-effectiveness of TEHV compared with bioprostheses was predicted from a societal perspective. Anticipated, but currently hypothetical improvements in performance of TEHV, divided in durability, thrombogenicity, and infection resistance, were explored in scenario analyses to estimate quality-adjusted life-year (QALY) gain, cost reduction, headroom, and budget impact. RESULTS: Durability of TEHV had the highest impact on QALY gain and costs, followed by infection resistance. Improved TEHV performance (- 50% prosthetic valve-related events) resulted in lifetime QALY gains of 0.131 and 0.043, lifetime cost reductions of €639 and €368, translating to headrooms of €3255 and €2498 per hypothetical TEHV compared to SAVR and TAVI, respectively. National savings in the first decade after implementation varied between €2.8 and €11.2 million (SAVR) and €3.2-€12.8 million (TAVI) for TEHV substitution rates of 25-100%. CONCLUSIONS: Despite the relatively short life expectancy of elderly patients undergoing SAVR/TAVI, hypothetical TEHV are predicted to be cost-effective compared to bioprostheses, commercially viable and result in national cost savings when biomedical engineers succeed in realising improved durability and/or infection resistance of TEHV.

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

A permutation two one-sided tests procedure to detect minimal fold changes of gene expression levels.

Current approaches to identifying differentially expressed genes are based either on the fold changes or on the traditional hypotheses of equality. However, the fold changes do not take into consideration the variation in estimation of the average expression. In addition, the use of fold changes is not in the frame of hypothesis testing, and hence the probability associated with errors for decision making of identification of differentially expressed genes cannot be quantified and evaluated. On the other hand, the traditional hypothesis of equality fails to take into consideration the magnitudes of the biologically meaningful fold changes that truly differentiate the genes between populations. Because of the large number of genes tested and small number of samples available for microarray experiments, the false positive rate for differentially expressed genes is quite high and requires further multiplicity adjustments, or use of an arbitrary cutoff for the p-values. However, all these adjustments do not have any biological justification. Hence, based on the interval hypothesis, Liu and Chow proposed a two one-sided tests procedure by consideration of both the minimal biologically meaningful fold changes and statistical significance simultaneously. To incorporate the correlation structure of expression levels among different genes and possible violation of normality assumption, we propose to apply a permutation method to the two one-sided tests procedure. A simulation study is conducted to empirically compare the type I error rate and power of the procedures based on the traditional hypothesis and the proposed permutation two one-sided tests procedure based on the interval hypothesis under various combinations of fold changes, variability, and sample sizes. Simulation results show that the proposed permutation two one-sided tests procedure based on the interval hypothesis not only can control the type I error rate at the nominal level but also provide adequate power to detect differentially expressed genes. Numerical data from public domains illustrate the proposed methods.

Self-assembly and ring-opening metathesis polymerization of cyclic conjugated molecules on highly ordered pyrolytic graphite.

Cyclic conjugated monomers comprising cyclopentadithiophene-vinylene trimers and their polymers on HOPG are observed using STM and AFM. ROMP of the monomers is performed using a Grubbs catalyst. Their STM images exhibit single chains of planar polymers, whereas their AFM images show elongation of the polymer chains on HOPG.

Clinical Performance of Prediction Rules and Nasogastric Lavage for the Evaluation of Upper Gastrointestinal Bleeding: A Retrospective Observational Study.

Introduction. The majority of patients with acute upper gastrointestinal bleeding (UGIB) are admitted for urgent endoscopy as it can be difficult to determine who can be safely managed as an outpatient. Our objective was to compare four clinical prediction scoring systems: Glasgow Blatchford Score (GBS) and Clinical Rockall, Adamopoulos, and Tammaro scores in a sample of patients presenting to the emergency department of a large US academic center. Methods. We performed a retrospective cohort study of patients during 2008-2010. Our outcome was significant UGIB defined as high-risk stigmata on endoscopy, or receipt of blood transfusion or surgery, or death. Results. A total of 393 patients met inclusion criteria. The GBS was the most sensitive for detecting significant UGIB at 98.30% and had the highest negative predictive value (90.00%). Adding nasogastric lavage data to the GBS increased the sensitivity to 99.57%. Conclusions. Of all four scoring systems compared, the GBS demonstrated the highest sensitivity and negative predictive value for identifying a patient with a significant UGIB. Therefore, patients with a 0 score can be safely managed as an outpatient. Our results also suggest that performing a nasogastric lavage adds little to the diagnosis UGIB.