In situ mycoremediation of acid rain and heavy metals co-contaminated soil through microbial inoculation with Pleurotus ostreatus.

The combined pollution of acid rain and heavy metals in soil is a pressing environmental problem, especially in the regions with large-scale heavy industrial production activities. Low remediation efficiency and weak long-lasting stability are major challenges when disposing the heavy metals contaminated soil in acid rain polluted sites. Herein, a specific microbe, strain CT13 was isolated and domesticated to exhibit high tolerance to both acid rain and cadmium (Cd). Then, an in situ mycoremediation method by adopting a bioaugmentation technology of strain CT13 inoculation with Pleurotus ostreatus was developed. The remediation performance was investigated in acidic conditions with Cd concentrations in soil ranging from 0 to 15 mg/kg. While most of the bacteria strains (e.g. strain CT6/13) significantly improved the dry weight of mushroom and Cd accumulation in neutral environment, the performance of strain CT6 was remarkably deteriorated in acid rain environment. In contrast, strain CT13 maintained its behavior in acidic conditions, displaying ∼30 % and 150 % enhancements (vs the neutral environment) in the dry weight of mushroom and Cd accumulation, respectively. In addition, inoculation of strain CT13 led to significant reductions in the content of superoxide dismutase, peroxidase and lipid peroxidation in the fruiting body of P. ostreatus, indicating an improvement in the mushroom's tolerance to both acid rain and heavy metals. The synergistic effect of strain CT13 and P. ostreatus realized the significant improvement in soil remediation efficiency and long-lasting stability in acidic conditions, providing valuable insights into the remediation of heavy metal contaminated soil in the regions affected by acid rain.

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

BACKGROUND: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. MATERIALS AND METHODS: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. RESULTS: Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). CONCLUSION: OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Clinical and Economic Outcomes in Patients With Metastatic Urothelial Carcinoma Receiving First-Line Systemic Treatment (the IMPACT UC I Study).

BACKGROUND: The IMPACT UC I study assessed real-world treatment patterns, outcomes, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic treatment after the FDA approval of 1L immune checkpoint inhibitor (ICI) monotherapy. PATIENTS AND METHODS: This retrospective study used 100% Medicare fee-for-service claims from 1/1/2015 to 6/30/2019 to identify patients aged ≥18 years diagnosed with UC with evidence of metastatic disease, continuously enrolled for 6 months before and after initial diagnosis. Patients were grouped by 1L treatment: cisplatin-containing chemotherapy, carboplatin-containing chemotherapy, ICI monotherapy, or nonplatinum-containing therapy. Unadjusted time on 1L treatment (TOT), overall survival (OS), HCRU, and total healthcare costs were analyzed. RESULTS: Of 18 888 patients with mUC, 8630 (45.7%) had received identified 1L systemic treatment; platinum-containing chemotherapy was the most common (cisplatin-containing chemotherapy, 37.6%; carboplatin-containing chemotherapy, 30.2%). Cisplatin- and carboplatin-containing chemotherapy had the shortest time-to-treatment initiation (median, 1.7-3.0 months) and longest TOT (median, 4.0-4.3 months). Median OS was longest with cisplatin-containing chemotherapy (20.0 months) and shortest with ICI monotherapy (7.6 months). Cisplatin- and carboplatin-containing chemotherapy were associated with highest HCRU; total healthcare costs were approximately 2-fold higher with ICI monotherapy vs other 1L treatments ($10 359 vs $5042-$5709 per patient per month). CONCLUSION: 1L platinum-containing chemotherapy resulted in the longest median OS and highest HCRU, whereas 1L ICI treatment had the shortest median OS and the highest costs. Over 50% of patients diagnosed with advanced UC (aUC) received no systemic therapy, highlighting the importance of optimal 1L treatment decisions in aUC.

Recent progress in nucleic acid detection with CRISPR.

Recent advances in CRISPR-based biotechnologies have greatly expanded our capabilities to repurpose CRISPR for the development of molecular diagnostic systems. The key attribute that allows CRISPR to be widely utilized is its programmable and highly specific nature. In this review, we first illustrate the principle of the class 2 CRISPR nucleases for molecular diagnostics which originates from their immunologic defence systems. Next, we present the CRISPR-based schemes in the application of diagnostics with amplification-assisted or amplification-free strategies. By highlighting some of the recent advances we interpret how general bioengineering methodologies can be integrated with CRISPR. Finally, we discuss the challenges and exciting prospects for future CRISPR-based biosensing development. We hope that this review will guide the reader to systematically learn the start-of-the-art development of CRISPR-mediated nucleic acid detection and understand how to apply the CRISPR nucleases with different design concepts to more general applications in diagnostics and beyond.

Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments.

Introduction: Mesenchymal-epidermal transition factor gene amplification (METamp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary METamp, as well as the testing procedures used to identify METamp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for METamp were also examined. Methods: Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps. Results: The median rate of primary METamp in NSCLC across the references was 4.8% (n=4 studies) and of secondary METamp (epidermal growth factor receptor [EGFR]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). METamp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of METamp NSCLC. Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines. Conclusion: Primary METamp occurs in approximately 5% of NSCLC cases, and secondary METamp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.

Isothermal Background-Free Nucleic Acid Quantification by a One-Pot Cas13a Assay Using Droplet Microfluidics.

High sensitivity and specificity nucleic acid detection has been achieved by the Cas13a collateral effect in combination with a separate recombinase polymerase amplification (RPA). However, these emerging methods cannot provide accurate quantification of nucleic acids because the two-step assay performance may be compromised if the RPA and Cas13a reactions are simply unified in a single step. In this work, we first addressed the challenges associated with enzymatic incompatibility and the macromolecular crowding effect in the one-pot assay development, making the consolidated RPA-Cas13a assay a facile and robust diagnostic tool. Next, we found that the one-pot reaction cannot precisely quantify the targets at low concentrations. Thus, by leveraging droplet microfluidics, we converted the one-pot assay to a digital quantification format, termed Microfluidics-Enabled Digital Isothermal Cas13a Assay (MEDICA). Due to the droplet compartmentation, MEDICA greatly accelerates the reaction and enables relative detection in 10 min and the end-point quantification in 25 min. Moreover, MEDICA facilitates the droplet binarization for counting because of background-free signals generated by trans-cleavage reporting of Cas13a. Our clinical validation highlights that CRISPR-based isothermal assays are promising for the next generation of nucleic acid quantification methods.

Droplet digital recombinase polymerase amplification (ddRPA) reaction unlocking via picoinjection.

Recombinase polymerase amplification (RPA) has been recognized as a promising isothermal amplification method for nucleic acid detection. However, the digital format of RPA is still challenging to implement due to its MgOAc-initiated reaction feature and the inherent non-specific amplification. Here we develop a Picoinjection Aided Digital reaction unLOCKing (PADLOCK) approach utilizing droplet microfluidics to achieve droplet digital RPA (ddRPA) for absolute nucleic acid quantification. By coupling a microfluidic picoinjector with a droplet generator, the reaction initiator MgOAc is dosed into droplets containing MgOAc-deprived RPA master mix for controlled digital reaction unlocking, which completely circumvents premature amplification. The discretization of the targets to a single-molecule level in confined droplets endows absolute quantification of the copy number. Coupled with CRISPR/Cas13a sensing, the ddRPA demonstrates single molecule detection ability within 30 min with significantly enhanced signal-to-noise ratio (S/N ratio>6) and uniform fluorescence signal reporting, facilitating the precise quantification of nucleic acids. Furthermore, the utility of the PADLOCK-CRISPR assay has been validated with 22 clinical samples, which generated results in 100% concordance with qPCR. We believe the coupling of droplet microfluidic technology with digital RPA will pave the way towards ultrasensitive and precise nucleic acid quantification.

Diagnostic and economic value of biomarker testing for targetable mutations in non-small-cell lung cancer: a literature review.

We aimed to assess the diagnostic and economic value of next-generation sequencing (NGS) versus single-gene testing, and of liquid biopsy (LBx) versus tissue biopsy (TBx) in non-small-cell lung cancer biomarker testing through literature review. Embase and MEDLINE were searched to identify relevant studies (n = 43) from 2015 to 2020 in adults with advanced non-small-cell lung cancer. For NGS versus single-gene testing, concordance was 70-99% and sensitivity was 86-100%. For LBx versus TBx, specificity was 43-100% and sensitivity was ≥60%. Turnaround times were longer for NGS versus single-gene testing (but not vs sequential testing) and faster for LBx versus TBx. NGS was cost-effective, and LBx reduced US per-patient costs. NGS versus single-gene testing and LBx versus TBx were concordant. NGS and LBx may be cost-effective for initial screening.

Plain language summary Patients with lung cancer with specific genetic mutations can benefit from medications that are specific to those mutations, known as targetable mutations. There are many methods to test for specific genetic mutations in patients with lung cancer. To detect genetic mutations, doctors can test the blood or urine, or they can test biopsy tissue; a small piece of the tumor removed from the lung. These tests can either look for mutations in one specific gene at a time, or they can use technology that reads the entire DNA sequence to observe multiple genes at once. In this review, we examined scientific reports to answer important questions about using genetic testing to find targetable mutations in patients with lung cancer. How accurate are different genetic tests? How fast can doctors get results from different genetic tests? How much do different genetic tests cost? We found that reading the entire DNA sequence was as accurate as testing one specific gene. Reading the entire DNA sequence takes more time than testing one specific gene, but it might reduce overall costs. Testing blood or urine was not as accurate as testing tissue, but it took less time for doctors to receive genetic test results and reduced costs.

Real-World Clinical Outcomes in Patients with Locally Advanced or Metastatic Merkel Cell Carcinoma Treated in U.S. Oncology Clinical Practices: Results from SPEAR-Merkel.

BACKGROUND: Immunotherapy (IO) has been associated with improved outcomes in patients with locally advanced Merkel cell carcinoma (laMCC) and metastatic Merkel cell carcinoma (mMCC). The primary objective of SPEAR-Merkel was to explore treatment patterns, clinical outcomes, and health care resource utilization (HCRU) in patients with laMCC or mMCC initiating first-line (1L) treatment with avelumab, non-avelumab IO, or chemotherapy in a U.S. community oncology setting. METHODS: Adult patients with laMCC or mMCC initiating 1L avelumab, non-avelumab IO, or chemotherapy from January 1, 2015, to March 31, 2019, were identified from the U.S. Oncology Network electronic health care record database and followed up through September 30, 2019. Baseline characteristics and HCRU were analyzed descriptively, including physician-stated overall response rate in the real-world clinical setting. Kaplan-Meier methods were used to measure duration of response, real-world progression-free survival (rwPFS), and overall survival (OS). RESULTS: Among the overall population (n = 94), 28 received 1L avelumab (9 laMCC, 19 mMCC), 26 received 1L non-avelumab IO (8 laMCC, 18 mMCC), and 40 received 1L chemotherapy (10 laMCC, 30 mMCC). The real-world overall response rate was 64.3%, 61.5%, and 42.5%, respectively. From 1L treatment initiation, median rwPFS was 11.4, 8.1, and 6.1 months, and median OS was 20.2 months, not reached, and 14.7 months for the respective cohorts. CONCLUSION: SPEAR-Merkel showed that patients with laMCC or mMCC treated with IO had improved outcomes compared with chemotherapy in clinical practice. The study provides insight on utilization and clinical outcomes associated with newer, more innovative therapies in clinical practice, which may help clinicians understand the variety of newer treatment options for both laMCC and mMCC. IMPLICATIONS FOR PRACTICE: To the authors' knowledge, SPEAR-Merkel is the first study to evaluate real-world clinical outcomes in patients with locally advanced Merkel cell carcinoma (laMCC) and metastatic Merkel cell carcinoma (mMCC) receiving first-line (1L) avelumab, non-avelumab immuno-oncology therapies, or chemotherapy in a real-world setting. SPEAR-Merkel showed clinical benefit for immuno-oncology therapies compared with chemotherapy. The study provides insight on uses and clinical outcomes associated with innovative therapies in clinical practice, which may help clinicians understand the variety of newer treatment options for both laMCC and mMCC. The study is of particular importance as it shows that chemotherapy is still being used as 1L treatment despite its inferior clinical and safety profile.

Effects of early vs delayed progression on clinical and economic outcomes in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors as first-line therapy: results from the IMPACT RCC claims data analysis.

BACKGROUND: A key therapeutic goal of metastatic renal cell carcinoma (mRCC) treatment is delayed disease progression. The degree to which early therapeutic success affects downstream outcomes is not well established. OBJECTIVE: To assess the clinical and economic impact of early vs delayed disease progression in patients with mRCC treated with first-line (1L) tyrosine kinase inhibitors (TKIs) followed by second-line (2L) therapy in the US Veterans Health Administration (VHA) database. METHODS: Adult patients newly diagnosed with mRCC who were treated with a TKI as 1L therapy and who progressed to 2L therapy from October 1, 2013, through March 31, 2018, were identified from the US VHA database. Patients were stratified by median time from initiation of 1L therapy to initiation of 2L therapy into early (median time or sooner)and delayed (longer than the median) progression cohorts. Clinical outcomes (time to 2L therapy discontinuation, time to third-line [3L] treatment initiation, and overall survival) were assessed descriptively, and health care resource utilization and costs were compared between patients in the early and those in the delayed progression cohorts. Survival analyses (Kaplan-Meier curves) were used to estimate descriptively the median time to discontinuation, time to next line of treatment, and time to death for each cohort. Multivariate analysis was performed to adjust for the influence of differences in cohort characteristics, and Cox proportional hazards models were used to descriptively assess the impact of predictive factors on clinical outcomes. RESULTS: 289 patients were included in the analysis: 145 in the early progression cohort and 144 in the delayed progression cohort. Baseline characteristics were similar between the early and delayed progression cohorts. Median time from 1L therapy initiation to 2L therapy discontinuation was 7.9 months in the early progression cohort and 18.0 months in the delayed progression cohort, whereas time from 1L therapy initiation to 3L therapy initiation was 9.4 and 21.8 months, respectively; overall survival was 19.7 and 36.4 months, respectively. Descriptive analysis revealed generally lower risks for 2L therapy discontinuation (HR = 0.40, 95% CI = 0.31-0.52), 3L therapy initiation (HR = 0.42, 95% CI = 0.32-0.55), and death (HR = 0.46, 95% CI = 0.33-0.64) for those with delayed progression. After adjustment for possible confounding factors, comparative analysis during the follow-up period showed that delayed progression was associated with a shorter median all-cause hospital length of stay (0.4 days vs 0.8 days for early progression; P = 0.0004), fewer pharmacy visits (3.57 vs 4.08 visits; P = 0.0266), and lower total health care costs ($10,342 vs $13,388; P = 0.0347) per patient per month. CONCLUSIONS: In patients with mRCC, early progression after 1L therapy initiation is associated with generally worse clinical outcomes and statistically significantly greater health care resource utilization and costs than delayed progression. This finding highlights the importance of initiating therapy with an optimal 1L treatment regimen that has been proven to delay disease progression. DISCLOSURES This study was sponsored by EMD Serono Inc., an affiliate of Merck KGaA, and Pfizer Inc. EMD Serono Inc. and Pfizer Inc. were involved in the study design; the collection, analysis, and interpretation of the data; the writing of the report; and the decision to submit the report for publication. Liu and Bhanegaonkar are employed by EMD Serono Inc., an affiliate of Merck KGaA. Kasturi was employed by EMD Serono Inc., an affiliate of Merck KGaA, at the time of this study. Kim and Krulewicz are employed by Pfizer Inc. Dieyi is an employee of STATinMED Research, which received consulting fees from EMD Serono Inc. and Pfizer Inc. Hutson has received grants from Pfizer Inc., Astellas Pharma Inc., Janssen Pharmaceuticals, Exelixis, Inc., and Eisai Co., Ltd., outside of this work. Data from this analysis were presented at the Virtual International Society for Pharmacoeconomics and Outcomes Research 2020 conference, May 18-20, 2020; the virtual American Society of Clinical Oncology Annual Meeting, May 29-31, 2020; and AMCP Nexus 2020 Virtual, October 20-23, 2020.

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: We investigated the association between adverse events (AEs) suspected to be immune-related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, or Merkel cell carcinoma. PATIENTS AND METHODS: We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S. commercial and Medicare Advantage with Part D enrollees in the Optum Research Database from March 1, 2014, through April 30, 2019. Claims were linked with mortality data from the Social Security Death Index and the National Death Index. Eligible patients had at least one ICI claim between September 1, 2014, and April 30, 2019. RESULTS: After adjusting for potential confounding variables, we found patients with AEs had more than double the risk of an inpatient stay (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.9-2.5) and an 80% higher risk of an emergency visit (HR, 1.8; 95% CI, 1.6-2.1) than patients without AEs. Adjusted 6-month total costs were $24,301 higher among patients with an AE versus those without ($99,037 vs. $74,736; 95% CI, $18,828-29,774; p < .001). Mean ± SD AE-related medical costs averaged $2,359 ± $7,496 per patient per month, driven by inpatient visits, which accounted for 89.9% of AE-related costs. Adjusted risk of mortality was similar in patients with and without AEs. CONCLUSION: Patients with AEs had higher risks of hospitalizations, emergency room visits, and higher health care costs, driven by inpatient stays, than patients without AEs. The adjusted risk of mortality was similar between the two cohorts. IMPLICATIONS FOR PRACTICE: Patients taking immune checkpoint inhibitors (ICIs) who had adverse events (AEs) had significantly higher health care costs and utilization, driven by inpatient stays, compared with patients who did not. Given this high cost associated with AEs and the differences in the side effect profile of ICIs versus traditional chemotherapy, it is important for physicians to be cognizant of these differences when treating patients with ICIs. Ongoing evaluation, earlier recognition, and more effective, multidisciplinary management of AEs may improve patient outcomes and reduce the need for costly inpatient stays.

Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel.

Aim: To assess clinical outcomes in patients with locally advanced (la) or metastatic (m) Merkel cell carcinoma (MCC) initiating first-line (1L) avelumab in a USA community oncology setting. Materials & methods: Adults with laMCC or mMCC initiating 1L avelumab were identified from The US Oncology Network electronic health record database and chart review. Results: Median overall survival and progression-free survival were not reached in laMCC (n = 9) vs 20.2 and 10.0 months in mMCC (n = 19); response rates were similar (66.7% vs 63.2%). Conclusion: This is the first study to show clinical benefit in patients with laMCC receiving 1L avelumab in a US real-world setting. Response rates in patients with mMCC were consistent with pivotal trials.

Lay abstract Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Because MCC progresses quickly, many patients have a poor prognosis. Avelumab is a type of drug that helps the patient's immune system to fight cancer. Avelumab was the first such drug approved by the US FDA for treating metastatic MCC based on the results of the JAVELIN Merkel 200 clinical trial. In SPEAR-Merkel, we studied how MCC patients with locally advanced as well as metastatic disease responded when they were treated with first-line avelumab in a real-world setting. These patients were from oncology practices in communities throughout the USA. Overall response rates in SPEAR-Merkel were comparable between patients with locally advanced and metastatic MCC. Importantly, we found that these patients experienced survival benefit similar to patients in the JAVELIN Merkel 200 (part B) study and other real-world studies.

Real-world symptoms, disease burden, resource use and quality of life in US patients with advanced renal cell cancer.

Aim: To assess symptoms, healthcare resource utilization and health-related quality of life in advanced renal cell carcinoma (aRCC) clinical practice. Materials & methods: The USA point-in-time survey of physicians and patients was conducted between February and September 2019. Results: Data were available for 227 patients. Mean (standard deviation) number of symptoms was 3.4 (3.2); differences were observed across International Metastatic RCC Database Consortium risk categories (p < 0.001), with fewer symptoms in favorable-risk patients. Disease burden, measured by greater healthcare resource utilization and worse health-related quality of life, was high, particularly in International Metastatic RCC Database Consortium intermediate- or poor- versus favorable-risk patients. In total, 45 patients (21.6%) were hospitalized due to aRCC within a 6-month period, 35 (16.8%) had one hospitalization and ten (4.8%) experienced ≥2 hospitalizations due to aRCC. Mean (standard deviation) 19-Item Functional Assessment of Cancer Therapy Kidney Symptom Index score was 53.6 (13.2) for this population, significantly lower than the reference value (59.8; p < 0.001). Conclusion: A clear need exists for improved disease management in patients with aRCC.

Lay abstract Late-stage/advanced renal cell carcinoma (aRCC) is kidney cancer that has spread to other body parts. aRCC is expensive to treat and affects patients in many ways. New treatments have become available, including tyrosine kinase inhibitors and immuno-oncology therapies. The type of treatment recommended depends on the patient's International Metastatic RCC Database Consortium risk score. This is a way of classifying patients as having a good, intermediate or poor survival risk. We asked physicians questions about their patients such as their age, how long they had aRCC, their treatment and symptoms, and asked patients how aRCC affected their lives, including how often they visited doctors and hospitals. aRCC had the greatest effect on patients with poor-risk scores. Those patients had more symptoms and worse quality of life than patients with intermediate or good risk scores. Treatment also affected patients' lives, although not as much as risk score. Patients with aRCC need better treatment options to help improve their quality of life.

Treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma: a real-world US study.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February-September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of 60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of 16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

Experience of establishing an acute geriatric outreach service versus subacute service to nursing homes.

To share our experience of establishing an acute outreach service to nursing homes and to evaluate the impact of such service on emergency department presentations, data were drawn from a pre-existing database from 2013 to 2017. Of the 986 acute patients treated in 12 nursing homes over a 23-month period, the acute geriatric outreach service was shown to be safe, with few adverse events (one allergic reaction) and 5.3% of patients required transfer to hospital. The acute service decreased emergency department presentation of nursing home patients by 10% compared to the subacute service (incidence rate ratio = 0.90; 95% confidence interval: 0.84-0.96; P = 0.001). Cost-benefit analysis showed for every $1 spent, a saving of $5 was realised.

Financial implications to Medicare from changing the dialysis modality mix under the bundled prospective payment system.

BACKGROUND: The economic burden of treating end-stage renal disease (ESRD) continues to grow. As one response, effective January 1, 2011, Medicare implemented a bundled prospective payment system (PPS, including injectable drugs) for dialysis patients. This study investigated the 5-year budget impact on Medicare under the new PPS of changes in the distribution of patients undergoing peritoneal dialysis (PD), in-center hemodialysis (ICHD), and home hemodialysis (HHD). METHODS: An Excel-based budget impact model was created to assess dialysis-associated Medicare costs. The model accounted for dialysis access establishment, the current monthly capitation physician payment for ESRD, Medicare dialysis payments (including start-up costs), training, oral drug costs, and the costs and probabilities of adverse events including access failure, hospitalization for access infection, pneumonia, septicemia, and cardiovascular events. United States Renal Data System (USRDS) data were used to project the US Medicare dialysis patient population across time. The baseline scenario assumed a stable distribution of PD (7.7%), HHD (1.3%) and ICHD (91.0%) over 5 years. Three comparison scenarios raised the proportions of PD and HHD by (1) 1% and 0.5%, (2) 2% and 0.75%, and (3) 3% and 1% each year; a fourth scenario held HHD constant and lowered PD by 1% per year. RESULTS: Under the bundled PPS, scenarios that increased PD and HHD from 7.7% and 1.3% over 5 years resulted in cumulative savings to Medicare of $114.8M (Scenario 1, 11.7% PD and 3.3% HHD at year 5), $232.9M (Scenario 2, 15.7% PD and 4.3% HHD at year 5), and $350.9M (Scenario 3, 19.7% PD and 5.3% HHD at year 5). When the PD population was decreased from 7.7% in 2013 to 3.7% by 2017 with a constant HHD population, the total Medicare payment for dialysis patients increased by over $121.2M. CONCLUSIONS: Under Medicare bundled PPS, increasing the proportion of patients on PD and HHD vs ICHD could generate substantial savings in dialysis-associated costs to Medicare.

Is there a difference in bloodstream infections in critically ill patients associated with ready-to-use versus compounded parenteral nutrition?

BACKGROUND & AIMS: Parenteral nutrition is widely used in critically ill patients receiving nutritional support. Several previous studies associated the use of parenteral nutrition with the development of bloodstream infections. This study compared bloodstream infections in critical care patients receiving parenteral nutrition (PN) prepared via conventional compounding versus premixed multichamber bags. METHODS: Records in the Premier Perspective™ database for all in patients ≥ 18 years of age, with a minimum 3-day intensive care unit stay, who received PN between 2005 and 2007 were analyzed (n = 15,328). Statistical analysis of data, grouped according to preparation method, compared differences in both observed bloodstream infection rates and adjusted rates, using logistic regression to examine the impact of hospital and patient baseline characteristics. RESULTS: Patients receiving compounded parenteral nutrition had longer intensive care unit stays (11.3 vs. 9.1 days) and longer hospital stays (22.6 vs. 19.4 days); both P < .001. After adjusting for baseline differences, the probability for bloodstream infections was 19% higher when using compounded parenteral nutrition vs. multichamber bags (29.6 vs. 24.9%; odd ratio = 1.29; 95% confidence interval = 1.06-1.59). CONCLUSION: In this retrospective review of a large patient database the adjusted probability of bloodstream infection was significantly lower in patients receiving multichamber bags than compounded parenteral nutrition. These findings need to be investigated further in high quality observational studies and prospective clinical trials.