bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of inpatient chemotherapy administration utilizing evaluation intervals.
Authors: Ramanathan Sabarina , Yenamandra Avani , Vuppala Aparna , Shan Khine , Lara-Martinez Hugo R. , Khan Rabia , Hanson Shaun Bryan , Safa Ahmed , McCormack Michael Joseph , Ward Kristine Marie , Styler Michael
Published: October 2019

75

Background: Inpatient chemotherapy requires an interdisciplinary approach to achieve shorter hospital stays and decrease cost. A quality improvement project at Hahnemann University Hospital was undertaken to identify delays in the process from admission to chemotherapy initiation in this population. Methods: Time stamps were recorded for patient arrival (door to floor), order placement (floor to order), and administration (order to chemo) to establish a baseline. A multidisciplinary team of pharmacy, nursing, and physicians was developed to address inefficiencies. There were three evaluation intervals: May - October 2015 (Part I), January 2017 - October 2018 (Part II) and October - December 2018 (Part III). Data collected from Part I established a baseline door-to-chemo time (DTC) of 7.2 hrs. Post Part I, prompt communication of patient arrival and delays in chemotherapy hanging were addressed. Part II interventions were outpatient consents and labs, timely order placement, and utilization of order sets. Pharmacy-nurse communication and equal distribution of patients through the week was implemented in Part III. The primary outcome measure was difference in DTC. Results: 200 admissions were reviewed. Results of the evaluation intervals are shown in Table. After the first evaluation interval, DTC improved from 7.18 to 5.96 hrs. DTC further decreased to 5.78 hrs post intervention II. The longest delay was between chemotherapy order and administration. Conclusions: DTC significantly improved between intervals with the above interventions. Utilizing a standardized nursing checklist and biweekly multidisciplinary meetings to emphasize prioritization will further decrease DTC. DTC reduction will decrease cost and increase patient satisfaction.

[Table: see text]
Implementation of standardized workflows to reduce inpatient length of stay for medical oncology patients.
Authors: Hooley Joseph , Koniarczyk Heather , Carrino Cheryl M. , Primm Kimberly , Westrick Curt , Brusio Michelle , Cummings Chad W.
Published: October 2019

80

Background: Reducing length of stay (LOS) is an important initiative for hospitals for both clinical and financial reasons. Patients who are hospitalized for extended lengths of time may be more susceptible to hospital-acquired infections and other complications. Reducing LOS can also decrease cost of care and allow for more streamlined patient throughput. Our institution sought to evaluate opportunities to reduce LOS for our medical oncology patient population. Methods: Several interventions were implemented to streamline discharge planning. The structure of rounding was evaluated and standardized on each inpatient oncology unit to ensure that it was multidisciplinary and occurred each day at an established time. A process was established for Advanced Practice Providers (APPs) to write prescriptions the day before discharge (delivered directly to the bedside), and for APPs to begin discharge of patients early the following morning with use of a new discharge checklist. Standardized workflow was also created for instances where prior authorizations were required for prescriptions. We partnered with our Home Care providers to streamline the process for patients anticipated to be discharged to that service. Partnership was also established with physical therapy (PT) to avoid ordering low-value consults and to provide enhanced education to nursing staff about early patient mobility. Another project is being piloted to move lab draws six hours earlier the night prior to discharge. This provides the medical team additional time to assess and treat based on lab results if the patient required blood product transfusions or electrolyte replacement prior to discharge. Results: Implementation of interventions began throughout the first several months of 2019. Each of the first four months of 2019 saw consecutive improvements in both observed average LOS and LOS observed-to-expected ratios. Overall, a 2% decrease was seen in both of these metrics when comparing January to April 2019 to the 2018 baseline. Conclusions: Implementing several interventions to streamline workflows and processes leading up to a patient’s discharge can be effective in reducing both overall LOS and LOS observed-to-expected ratios.
The Oncology Evaluation Center: Implementation of a same-day evaluation and treatment center to avoid unnecessary ED visits.
Authors: Zinck Lindsey , McGettigan Suzanne , Braun Jennifer , Walsh Abbey , Cullen Lauren
Published: October 2019

81

Background: Oncology patients have high rates of both Emergency Department (ED) visits and readmissions. The Hematology-Oncology Division at this urban, 776-bed academic medical center established the Oncology Evaluation Center (OEC) to provide cancer patients with prompt ambulatory evaluation for new symptoms that may otherwise lead to ED visits and unplanned admissions. With new therapeutic options associated with unique complications, the OEC Advanced Practice Providers are knowledgeable in providing care to this high-risk population. ED providers can lack oncology-specific training, comfort, and confidence when caring for cancer patients, resulting in sub-optimal care. Methods: A retrospective review of the chief complaints (CC) of oncology patients presenting to the ED was conducted. Using Plan Do Study Act methodology, in 2016 the OEC was opened to provide same day evaluations and interventions to patients with symptoms related to their cancer diagnosis, their treatment, or their comorbidities. Inclusion and exclusion criteria were developed to ensure appropriate referrals to the OEC. A hospital awareness campaign launched to promote OEC referrals, including educational sessions at multidisciplinary tumor boards. Additionally, two Lean Six Sigma trained infusion RNs led initiatives to promote OEC utilization. Results: The OEC resulted in quick evaluation and intervention for oncology patients. The most common CC are pain, dehydration, fever, nausea/vomiting, and fatigue. Of the 2721 patients seen to date in the OEC, 72% were discharged to home. According to survey results, 81% of oncology providers agree that if the OEC were not in existence, patients referred to the OEC would be referred to the ED. Oncology readmission rates have decreased from 14% (2016) to 12% (2018). Conclusions: The OEC has proven to be an innovative solution for prompt evaluation and ambulatory treatment of cancer patients with complications. This is a valuable component of comprehensive patient-focused care, resulting in ED visit and readmission avoidance. The OEC is an effective low cost, high reward programmatic strategy to expand access to care while improving patient experience.
Pharmacy involvement in an oral anticancer management program: Drug acquisition and safety in an ambulatory comprehensive care center.
Authors: Szabatura Audrea H , Kaymakcalan Marina D. , Cao Cathy , Nguyen Phuong
Published: October 2019

85

Background: Oral anticancer agents (OACA) offer benefits of convenience, flexibility and quality of life; however, similar to intravenous therapy, OACA can be prone to medication ordering errors, drug-interactions, and administration errors. Additionally, they carry unique challenges such as treatment delay due to acquisition barriers and errors related to self-administration and monitoring. An oral anticancer management program was implemented to address vulnerable aspects of the outpatient OACA medication use process. Pharmacy benefit specialists (PBS) assist with prior authorizations (PA) and drug acquisitions; while, clinical pharmacists perform medication assessments and patient education. Methods: A retrospective review of patients prescribed OACAs between January 1 - March 31, 2019 was performed. A review of all PAs facilitated by our PBS was conducted and included date of prescription, date of submission to insurance, and date of PA approval. An assessment of pharmacist interventions on the prevention of medication-related errors and toxicity was conducted and was defined by any clarification or recommendation regarding medication dose, administration instructions, drug interactions, symptom management, medication reconciliation, and/or medication monitoring. Results: A total of 567 PAs were processed. Twenty-eight PA requests were denied and 539 were approved. The average time to approval was 1.5 days (range 0-13 days). 299 of the 567 patients were prescribed a new OACA and were enrolled into our education program. Pharmacists educated 191 patients. Pharmacists intervened 175 times for the 191 patients counseled. Interventions included recommendations/clarifications for symptom management (21.5%), medication reconciliation (19.5%), drug administration (16.2%), drug interactions (13.6%), and medication monitoring (7.3%). Conclusions: Pharmacy staff can make a valuable contribution to drug acquisition and overall clinical care of patients receiving OACAs. Our PBS reduced delays in acquisition and clinical pharmacists minimized medication-related errors and toxicity.
Successful creation of an outpatient team-based model for traditionally inpatient chemotherapy.
Authors: Kubal Timothy Edward , Salamanca Christopher , Tobon Katherine , Lubas Amber , Frantz Diedra K. , Nelson Rebecca , Smith Melissa , Wartenberg Karen , Lancet Jeffrey E.
Published: October 2019

86

Background: In 2014, due to increased demand for inpatient hospital beds and subsequent patient dissatisfaction due to delays for patients receiving scheduled chemotherapy, Moffitt Cancer Center created a multi-disciplinary team to transition traditionally inpatient chemotherapy regimens into the outpatient setting. Methods: A Team composed of Physicians, Pharmacists, PA’s/ARNP’s, Social work, Infusion Nursing and IT drove initiation and implementation of new processes from 2014-Current with gradual increases in patient volumes and continued high quality and patient safety. Results: Over the examined 5 year time period, HyperCVAD Arm A, DA-EPOCH, Blinatumomab and Liposomal Daunorubicin and Cytarabine (Vyxeos) were transitioned into the outpatient setting. 667 total cycles of chemotherapy were transitioned into the outpatient setting, saving 4,386 inpatient days over the examined time period. Hospitalization was required in 22 of 667 cycles (3.3%) with no attributable mortality due to outpatient administration. Examination of potential financial impact was consistent with an estimated favorable impact to overall margin of $3,153,534 due to backfill of inpatient beds. Conclusions: Outpatient delivery of traditionally inpatient chemotherapy is safe and effective with the potential for reduction in delays for scheduled chemotherapy patients and favorable financial impact. Critical to success is the creation of an empowered, cross functional leadership team and a gradual and sequential approach to implementation.
Development of a multidisciplinary approach to supportive care for patients with genitourinary cancers.
Authors: Yocavitch Liana , Garber Gregory D. , Petok Alison , Worster Brooke , Handley Nathan
Published: October 2019

88

Background: Patients with cancer who engage early with palliative care may experience improved quality of life (QOL), increased overall survival (OS), and decreased acute care utilization. The Neu Center for Supportive Medicine and Cancer Survivorship (NCSMC) at Thomas Jefferson University is a program designed to identify patients who would benefit from early intervention palliative and supportive care and deliver appropriate services. After initial experience with the model in patients with gastrointestinal and head and neck malignancies, the NCSMC is expanding to patients with genitourinary cancers. Methods: A multidisciplinary team consisting of palliative care physicians, social work, psychology, and navigation conducts biopsychosocial screening (using the NCCN Distress Thermometer) and initiates a personalized care plan for each patient to clarify treatment goals and offer assistance. Prior to deploying the program, multiple stakeholders were engaged to discuss optimal screening points in the patient journey. Patients with a new cancer diagnosis are approached at a post-operative visit in the urology clinic; patients with high distress or significant barriers are discussed at a weekly interdisciplinary meeting with a team of physicians, nurses, social workers, and psychiatry. Patients are subsequently referred to services identified as potentially beneficial. Results: In the first 10 weeks of the program, 67 patients with new diagnoses of bladder (28, 41.8%), prostate (21, 31.3%), kidney (12, 17.9%), urothelial (5, 7.5%), and testicular (1, 1.5%) cancers were screened. 38 (59.4%) patients were identified as low distress; 24 patients (36%) were identified as high distress and offered NCSMC services. Two patients utilized services. Conclusions: Distress and barriers to care amongst patients with newly diagnosed genitourinary cancers are highly variable. While evaluating all patients in the immediate post-operative period is effective at identifying affected patients, the process is resource intensive. An iterative approach testing the intervention at different points in the patient journey is ongoing. As the program matures, impact on QOL, OS, and utilization will be measured.
Implementing an early discharge initiative for patients receiving high-dose methotrexate.
Authors: Binder Adam , Burdette Samantha , Galanis Patricia , Birchmeier Katlin , Handley Nathan , Piddoubny Maria
Published: October 2019

90

Background: Over 70% of patients are hospitalized in the first year after a cancer diagnosis. While some admissions are unplanned and potentially preventable, many are planned admissions for intensive chemotherapy. High Dose Methotrexate (HD-MTX) is commonly used for the treatment of osteosarcoma or CNS involvement in lymphoproliferative neoplasms. It is given in the inpatient setting due to monitoring requirements after administration. We postulated that changing discharge criteria for HD-MTX from 0.05 µmol/L to ≤0.1 µmol/L would be feasible and safe, and would reduce length of stay (LOS) for patients receiving HD-MTX. Cost savings were also calculated. Methods: Following an assessment of drivers of LOS amongst patients receiving HD-MTX, we identified discharge criteria as an actionable factor. We developed a workflow to discharge patients with 3 days of oral leucovorin and sodium bicarbonate when MTX level reached ≤0.1 µmol/L. Patient demographics, chemotherapy regimen, cycle, dose, and LOS data were collected for a 7 month period before and a 4 month period after the intervention. Cost savings were estimated based on the daily cost of a hospital bed at the institution. Results: Mean LOS for the pre-intervention and post-intervention group was 4.84 days (n=49) and 3.67 days (n=42), respectively (p=0.007). This resulted in a 24.4% reduction in length of stay. Average reduction in LOS of 1.17 days resulted in a decrease in cost of $1,828.73 per admission, with a 4 months savings of $76, 806.56 and projected annualized savings of $230,419.67. No patient experienced complications because of change in discharge criteria. Conclusions: Liberalizing discharge criteria for HD-MTX is feasible, safe, and cost-effective. Further efforts to reduce LOS for elective chemotherapy admissions or safely transition some of these complex regimens to the home setting are currently underway at our institution.
Health insurance literacy, status, and financial toxicity in women receiving treatment for metastatic breast cancer.
Authors: Williams Courtney , Ingram Stacey A. , Lawhon Valerie , Wan Clara , Kenzik Kelly , Azuero Andres , Pisu Maria , Young Pierce Jennifer , Lowman Janel , Jones Jonathan , Dekle Kendal , Mennemeyer Stephen T. , Nipp Ryan David , Rocque Gabrielle Betty
Published: October 2019

96

Background: Though uninsurance rates declined after the Affordable Care Act, the number of underinsured, or individuals who spend > 10% of their income on out-of-pocket (OOP) medical costs, continues to rise. In patients with metastatic breast cancer (MBC), underinsurance may lead to financial toxicity (FT), or patient-level financial burden and distress, since diagnosis and treatment is extremely costly. This study explores health insurance literacy and the association between FT and health insurance status in women receiving treatment for MBC. Methods: This cross-sectional study utilized survey data collected from 2017-2019 in women age ≥18 receiving treatment for MBC at two academic medical centers in Alabama. FT was measured by the Comprehensive Score for Financial Toxicity (COST) tool (11-item scale from 0-44, with lower scores indicating worse FT). Health insurance status and OOP costs were self-reported. Effect sizes were calculated using Cohen’s d or Cramer’s V. Mixed and generalized linear models clustered by site and treating medical oncologist estimated the association between FT and health insurance status. Results: In 81 women with MBC, median COST score was 24 (interquartile range [IQR] 17-30), 44% had private insurance, 40% Medicare, and 16% Medicaid. Though 25% and 33% of surveyed patients did not know their health insurance premium or deductible cost, respectively, privately insured patients more often knew the cost of their premiums (97%; V = 0.58) and deductibles (81%; V = 0.33) compared to publicly insured patients. In adjusted models, FT levels did not differ significantly based on health insurance type (private insurance COST 21, 95% confidence interval [CI] 18-25; Medicaid COST 23, 95% CI 17-29; Medicare COST 24, 95% CI 20-27). However, risk of severe FT (COST ≤13) was 147% higher for privately insured patients versus Medicare beneficiaries (risk ratio 2.47, 95% CI 1.44-4.21). Conclusions: Despite higher levels of health insurance literacy, privately insured patients receiving treatment for MBC may be at increased risk of severe FT. Further research is needed to understand causes of underinsurance in patients with MBC, which could lead to cancer-related FT.
Outcomes of immunotherapy administration for hospitalized cancer patients.
Authors: Dougherty David W. , Leblebjian Houry , Duperrault Megan , Awad Mark M. , Bartel Sylvia , McDonnell Anne , Bunnell Craig A. , Wagner Andrew J. , Pandya Chintan , Hamel Lauren M. , Glotzbecker Brett
Published: October 2019

98

Background: With approvals across multiple cancer types and favorable toxicity profiles, oncologists may consider using immunotherapy (IMT) while their patients are hospitalized. Inpatient IMT may be cost-prohibitive to administer for most institutions due to high cost and inpatient payment structure, but little data are available to evaluate outcomes for IMT in hospitalized patients. We investigated the survival benefit of administering IMT to hospitalized patients with cancer at an NCI-designated cancer center. Methods: We conducted a retrospective chart review of all patients receiving ipilimumab, nivolumab, or pembrolizumab during inpatient admission at Dana-Farber Cancer Institute/Brigham & Women’s Hospital in 2017. For each patient, we assessed: total dose, indication for dosing, cancer type, time between dose and discharge, time between discharge and death, and total cost (average wholesale price). Study follow up was January 1, 2017 to July 1, 2018. Results: Fifty doses of IMT were administered to 44 patients. Most patients (40) received 1 dose, 2 patients received 3 doses, 1 patient received 2 doses, and 1 patient received a combination of ipilimumab/nivolumab. The most common cancer types were lung (41%), gastrointestinal (18%), and head and neck (16%). Indications for IMT administration were: patient due for next dose (48%), disease progression (42%), and new diagnosis (11%). The majority of doses (70%) were received within 7 days prior to discharge, with 32% of doses within 1 day of discharge. The majority of patients (86%) died in the study period; 14% of patients died during admission. Average survival between discharge and death was 54 days (range: 0-444 days). Total cost of inpatient IMT administration was $413,370, an average of $9,395 per patient. Conclusions: To our knowledge, this is the largest analysis of outcomes for patients receiving IMT during a hospitalization. Inpatient use of IMT in cancer patients is associated with high cost and poor clinical outcomes. Dosing within one week prior to hospital discharge was common. Clinical factors such as PD-L1 status, disease status, and reason for admission, which may be important to understand which patients may benefit most from inpatient IMT, should be examined.
Treatment patterns and cost of care in commercially insured relapsed acute myeloid leukemia (AML) patients in the outpatient setting.
Authors: Qian Chunlin , Lin Feng , Kwong Jackie
Published: October 2019

99

Background: Outpatient administration of cancer therapy has become more common in recent years. The objective of this study was to evaluate treatment patterns and cost of care for relapsed AML patients in the outpatient setting. Methods: A retrospective analysis was performed using the IQVIA Health Plan Claims Data–US database. Patients were eligible if they had at least one outpatient claim associated with relapsed AML diagnosis as identified by ICD-9 (205.02) and ICD-10 (C92.02, C92.42, C92.52, C92.62, C92.A2) codes between 1/1/2009 to 12/31/2017, had no inpatient claim for AML diagnosis within 30 days of index claim, and received treatment for relapsed AML as recommended by NCCN guidelines within 30 days of index outpatient claim. Utilization of high intensity chemotherapy (HIC), hypomethylating agent (HMA), low-dose cytarabine (LoDAC) and sorafenib, duration of treatment and the cost per 28-day treatment cycle were examined. Patients were censored at either treatment switching or end of follow-up. Results: Of the 6,242 patients with relapsed AML diagnosis in the IQVIA™ database, 709 did not have inpatient claim of which only 281 patients [26.0% >65 years; 43.8% females] met inclusion criteria and received a total of 1,336 treatment cycles of NCCN recommended treatment as outpatient. About 75% of patients (n=209) received HMA, 6% (n=17) received HIC and 19.6% (n=55) received LoDAC. Patients >65 years were more likely to receive HMA than HIC and LoDAC (p=0.003). Mean (SD) number of treatment cycles for HMA, high-intensity chemotherapy and LoDAC was 5.7 (5.2), 1.2 (0.4) and 2.2 (1.4), respectively. Sorafenib was used in 4.8%, 17.6% and 3.6% patients treated with HMA, HIC and LoDAC. Mean (SD) cost per cycle was $11,246 (8,895), $10,620 (16,722), $3,254 (2,948), and $10,799 (3,057) for HMA, HIC, LoDAC and sorafenib, respectively. Conclusions: Treatment for relapsed AML in the outpatient setting without hospitalization was uncommon during the study period. Low-intensity regimens remain the mainstay of therapy in the outpatient setting, suggesting that treatment toxicities and monitoring requirement are key determinants for treatment setting for relapsed AML.
Combined PIK3CA and FGFR Inhibition With Alpelisib and Infigratinib in Patients With PIK3CA-Mutant Solid Tumors, With or Without FGFR Alterations
Authors: Hyman David M. , Tran Ben , Paz-Ares Luis , Machiels Jean-Pascal , Schellens Jan H. , Bedard Philippe L. , Campone Mario , Cassier Philippe A. , Sarantopoulos John , Vaishampayan Ulka , Chugh Rashmi , Mahipal Amit , Lockhart A. Craig , Sessa Cristiana , Zander Thomas , Ng Matthew , Curigliano Giuseppe , Bendiske Jennifer , Chen Xueying , Choudhury Somesh , Graus-Porta Diana , Lewis Nancy , Perez Garcia Jose Manuel , de Miguel-Luken María José
Published: October 2019

PURPOSE

Concurrent PIK3CA mutations and fibroblast growth factor receptor (FGFR) alterations occur in multiple cancer types, including estrogen receptor–positive breast cancer, bladder cancer, and endometrial cancer. In this first-in-human combination trial, we explored safety and preliminary efficacy of combining the PI3Kα selective inhibitor alpelisib with the FGFR1-4 selective inhibitor infigratinib.

PATIENTS AND METHODS

Patients with PIK3CA-mutant advanced solid tumors, with or without FGFR1-3 alterations, were enrolled in the dose escalation or one of three molecular-defined dose-expansion cohorts. The primary end point was the maximum tolerated dose. Secondary end points included safety, pharmacokinetics, and response. Archival tumor samples were sequenced to explore genomic correlates of response.

RESULTS

In combination, both agents were escalated to full, single-agent recommended doses (alpelisib, 300 mg per day continuously; infigratinib, 125 mg per day 3 weeks on followed by 1 week off). The toxicity profile of the combination was consistent with the established safety profile of each agent, although 71% of all patients required at least one treatment interruption or dose reduction. Molecularly selected dose expansions in breast cancer and other solid tumors harboring PIK3CA mutations, alone or in combination with FGFR alterations, identified sporadic responses, predominately in tumor types and genotypes previously defined to have sensitivity to these agents.

CONCLUSION

The combination of alpelisib and infigratinib can be administered at full single-agent doses, although the high rate of dose interruption or reduction suggests long-term tolerability may be challenging. In exploratory signal-seeking cohorts of patients harboring dual PIK3CA and FGFR1-3 alterations, no clear evidence of synergistic activity was observed.
Is Testicular Germ Cell Cancer Estrogen Dependent? The Role of Endocrine Disrupting Chemicals
Authors: Fénichel Patrick , Chevalier Nicolas
Published: October 2019

Testicular germ cell cancer (TGCC) is the most frequent cancer of the young male, with an increasing incidence worldwide. The pathogenesis and reasons for this increase remain unknown. However, epidemiological and experimental data have suggested that, similar to genital malformations and sperm impairment, it could result from the interaction of genetic and environmental factors including fetal exposure to endocrine-disrupting chemicals (EDCs) with estrogenic effects. In this review, we analyze the expression of classic and nonclassic estrogen receptors by TGCC cells, the way they may influence germ cell proliferation induced by EDCs, and discuss how this estrogen dependency supports the developmental and environmental hypothesis.
Toward a Local Queer Aesthetics
Authors: Ula Duygu
Published: October 2019

Focusing on photographs by Nilbar Güreş, a visual and performance artist, this article analyzes how her images deconstruct and reimagine the various identities of the Turkish nation and Western discourses of homosexuality at once. By depicting seemingly conventional women in traditional settings (such as the living room and the mosque) and imbuing them with a queer currency of desire, Güreş calls into question the stability of national and cultural narratives about these women’s lives as well as the stereotypes of an increasingly globalizing queer culture. Through close readings and cultural and political contextualization, the article positions her work vis-à-vis the tensions between global and local, rural and urban, traditional and marginal, and argues that her images form a visual archive of local queer aesthetics that positions itself in opposition to both national discourses of gender and sexuality in the contemporary Turkish context and Western-centric discourses of queerness.
Malignant Peritoneal Mesothelioma: Patterns of Care and Survival in the Netherlands: A Population-Based Study
Authors: de Boer Nadine L. , van Kooten Job P. , Damhuis Ronald A. M. , Aerts Joachim G. J. V. , Verhoef Cornelis , Madsen Eva V. E.
Published: October 2019

Background

Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. Recently, focus has shifted toward a more aggressive and multimodal treatment approach. This study aimed to assess the patterns of care and survival for MPM patients in the Netherlands on a nationwide basis.

Methods

The records of patients with a diagnosis of MPM from 1993 to 2016 were retrieved from the Dutch Cancer Registry. Data regarding diagnosis, staging, treatment, and survival were extracted. Cox regression analyses and Kaplan–Meier survival curves were used to study overall survival.

Results

Between 1993 and 2016, MPM was diagnosed for 566 patients. Overall, the prognosis was very poor (24% 1-year survival). The most common morphologic subtype was the epithelioid subtype (88%), followed by the biphasic (8%) and sarcomatoid (4%) subtypes. Surgical treatment has become more common in recent years, which most likely has resulted in improved survival rates. In this study, improved survival was independently associated with hyperthermic intraperitoneal chemotherapy (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.21–0.55) and surgery with adjuvant systemic chemotherapy (HR, 0.33; 95% CI, 0.23–0.48). Nonetheless, most patients (67%) do not receive any form of anti-cancer treatment.

Conclusion

This study indicated that MPM still is a rare and fatal disease. The survival rates in the Netherlands have improved slightly in the past decade, most likely due to more aggressive treatment approaches and increased use of surgery. However, most patients still do not receive cancer-directed treatment. To improve MPM management, and ultimately survival, care should be centralized in expert medical centers.
Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases
Authors: Enblad Malin , Graf Wilhelm , Terman Alexei , Pucholt Pascal , Viklund Björn , Isaksson Anders , Birgisson Helgi
Published: October 2019

Purpose

Genetic alterations in colorectal peritoneal metastases (PM) are largely unknown. This study was designed to analyze whole-genome copy number alterations (CNA) in colorectal PM and to identify alterations associated with prognosis after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

All patients with PM, originating from a colorectal adenocarcinoma, who were treated with CRS and HIPEC in Uppsala Sweden, between 2004 and 2015, were included (n = 114). DNA derived from formalin-fixed paraffin-embedded (FFPE) specimens were analyzed for CNA using molecular inversion probe arrays.

Results

There were extensive but varying degrees of CNA, ranging from minimal CNA to total aneuploidy. In particular, gain of parts of chromosome 1p and major parts of 15q were associated with poor survival. A combination of gains of 1p and 15q was associated with poor survival, also after adjustment for differences in peritoneal cancer index and completeness of cytoreduction score [hazard ratio (HR) 5.96; 95% confidence interval (CI) 2.19–16.18]. These patients had a mean copy number (CN) of 3.19 compared with 2.24 in patients without gains. Complete CN analysis was performed in 53 patients. Analysis was unsuccessful for the remaining patients due to insufficient amounts of DNA and signals caused by interstitial components and normal cells. There was no difference in survival between patients with successful and unsuccessful CN analysis.

Conclusions

This study shows that gains of parts of chromosome 1p and of major parts of chromosome 15q were significantly associated with poor survival after CRS and HIPEC, which could represent future prognostic biomarkers.
Mutations in the anticodon stem of tRNA cause accumulation and Met22-dependent decay of pre-tRNA in yeast
Authors: Payea Matthew J. , Hauke Alayna C. , De Zoysa Thareendra , Phizicky Eric M.
Published: October 2019

During tRNA maturation in yeast, aberrant pre-tRNAs are targeted for 3′–5′ degradation by the nuclear surveillance pathway, and aberrant mature tRNAs are targeted for 5′–3′ degradation by the rapid tRNA decay (RTD) pathway. RTD is catalyzed by the 5′–3′ exonucleases Xrn1 and Rat1, which act on tRNAs with an exposed 5′ end due to the lack of certain body modifications or the presence of destabilizing mutations in the acceptor stem, T-stem, or tRNA fold. RTD is inhibited by mutation of MET22, likely due to accumulation of the Met22 substrate adenosine 3′,5′ bis-phosphate, which inhibits 5′-3′ exonucleases. Here we provide evidence for a new tRNA quality control pathway in which intron-containing pre-tRNAs with destabilizing mutations in the anticodon stem are targeted for Met22-dependent pre-tRNA decay (MPD). Multiple SUP4οc anticodon stem variants that are subject to MPD each perturb the bulge-helix-bulge structure formed by the anticodon stem–loop and intron, which is important for splicing, resulting in substantial accumulation of end-matured unspliced pre-tRNA as well as pre-tRNA decay. Mutations that restore exon–intron structure commensurately reduce pre-tRNA accumulation and MPD. The MPD pathway can contribute substantially to decay of anticodon stem variants, since pre-tRNA decay is largely suppressed by removal of the intron or by restoration of exon–intron structure, each also resulting in increased tRNA levels. The MPD pathway is general as it extends to variants of tRNATyr(GUA) and tRNASer(CGA). These results demonstrate that the integrity of the anticodon stem–loop and the efficiency of tRNA splicing are monitored by a quality control pathway.
Evaluation of post-bleaching hypersensitivity using desensitizing agent before and /or after in-office bleaching: A randomized clinical trial.
Authors: Sabry Tawfik Silvia , Khairy Mohamed Adel Ezzat , ElBaz Maha Abd Elsalam , El korashy Maha Ebrahim Mohamed
Published: October 2019

Background: Dental bleaching has become one of the most demanded aesthetic procedures as it is very simple and gives fast results that satisfy the patient’s wishes. However, unfortunately, it has the annoying side effect of tooth sensitivity. This clinical trial was designed to evaluate the efficacy of using a desensitizing agent, which was applied during in-office bleaching with 30% HP (hydrogen peroxide).

Methods: 36 participants were divided into four groups (N = 9). According to the intended intervention as follows: Group I:—Application of Relief ®Amorphous Calcium Phosphate (ACP) before in-office bleaching; Group II—Application of Relief ®ACP before and after in-office bleaching; Group III—Application of Relief ®ACP after in-office bleaching; and Group IV: placebo was applied before and after in-office bleaching.  Then, three hydrogen peroxide bleaching applications for a total of 45 minutes were performed. The primary outcome variable was hypersensitivity, assessed with (VAS) scale immediately and 24h, 1 week and 1 month after the procedure; while the secondary outcome was teeth shade assessed using the VITAPAN ® classical shade guide.

Results: Statistical analysis was done using Kolmogorov-Smirnov, Shapiro-Wilk tests, Kruskal-Wallis test and Dunn’s test. Immediately after bleaching, there was statistically significant distinction in the median pain score between the groups. After 1 day, the ACP gel before and after bleaching group showed the lowest median score, while, the control group confirmed the highest median score. After 2 days, no statistically sizable difference was observed between all groups. The group receiving ACP gel before and after showed the highest change in median of classical shade guide scores while, (ACP gel after) and control group; showed the lowest change.

Conclusion: The application of the desensitizing agent prior to and after in–office bleaching was successful in lowering post-bleaching hypersensitivity.

Trail Registration: Clinical trial.gov NCT02942082 21/10/2016
ROLE OF HYPERCORTISOLEMIA IN PROGRESSION OF THE COMORBID COURSE OF CORONARY ARTERY DISEASE, DIABETES MELLITUS TYPE 2 AND ANEMIA
Authors: Pavliukovych Nataliia , Pavliukovych Oleksandr , Buriak Oleksandr , Kopchuk Tamara , Vivsyannuk Volodymyr
Published: October 2019

INTRODUCTION: Hyperactivation of stress-limiting mechanisms of the organism is a unique physiological response of the human being to chronic hypoxia of different origins.

OBJECTIVES: Investigation of dynamics of cortisol synthesis changes in patients with coronary artery disease with comorbid diabetes mellitus type 2 and anemic syndrome in patients of older age groups.

METHODS: Blood cortisol level was measured in 40 old and senile coronary artery disease patients with comorbid diabetes mellitus type 2 and anemic syndrome of different degrees of severity. The control group consisted of 12 patients with coronary artery disease without comorbidities that were not significantly different through gender and age from the patients of the research groups. Possible effects of telmisartan on the degree of chronic hypoxia were also investigated.

RESULTS: In patients of old and senile age with coronary artery disease  and comorbid anemic syndrome, same as in case of coronary artery disease and anemic syndrome on the background of diabetes mellitus type 2, activation of the cortisol synthesis is observed, likely in response to hypoxia as a stress factor in anemia. The degree of severity of the detected changes was different depending on the degree of anemia severity. There was no normalization of cortisol content in blood in any of the major experimental groups regardless the prescribed treatment with ACE inhibitors or telmisartan.

CONCLUSIONS: In patients with coronary artery disease, same as in the case of a comorbid course of coronary artery disease and diabetes mellitus type 2, an increase of cortisol secretion in response to anemic hypoxia was observed. As the degree of severity of the anemic syndrome progressed, gradual decreasing of cortisol blood level was detected. Reduction of the intensity of stress-limiting systems in the organism by telmisartan prescription may help to eliminate the adverse effects of hypercortisolemia on the progression of coronary artery disease, especially on the background of comorbid diabetes mellitus type 2 and anemia.
EPIDEMIOLOGY AND RISK FACTORS OF SUDDEN DEATH DUE TO PULMONARY THROMBOEMBOLISM: A RETROSPECTIVE STUDY
Authors: Šimakauskas Rokas , Baltuonis Martinas , Laima Sigitas , Chmieliauskas Sigitas , Fomin Dmitrij , Jasulaitis Algimantas , Stasiūnienė Jurgita
Published: October 2019

Introduction. Pulmonary thromboembolism (PTE) is not an uncommon cause of sudden, unexpected death. Autopsy is the gold standard for cause of death determination in cases of suspected PTE. Mortality rates due to PTE are not estimated accurately.

Objective. The aim of this study was to analyze distribution patterns and risk factors of sudden deaths due to PTE.

Methods. Retrospective analysis of Lithuanian State Forensic Medicine Service autopsy data, period 2014-2018. A total of 4533 cases were reviewed; 80 cases met the criteria of immediate cause of death being PTE and were included in the study. PTE epidemiology, risk factors, clinical and pathoanatomical characteristics were described by reviewing scientific literature and statistical databases.

Results. PTE as the cause of sudden death was diagnosed in 37(46.25%) men and 43(53.75%) women. Median age at the time of death was 62.8±17.2 years. Death occurred in hospital in 21(26.25%) cases. Trauma was the underlying cause of PTE in 11(13.75%) cases; 9(81.8%) patients were admitted to hospital after a traumatic event. Cardiac hypertrophy was observed in 70(87.5%) autopsies. Abdominal subcutaneous fat thickness was 4.08±2.64 cm in men and 5.35±2.69 cm in women. Deep vein thrombosis (DVT) was confirmed upon microscopic examination in all cases, being the underlying cause of death in 67(83.75%) cases.

Conclusion. Sudden death due to PTE usually occurs at an older age and in absence of medical care. PTE is common after sustaining severe traumatic injuries which, when not immediately lethal, are managed in hospital. Cardiac hypertrophy and obesity may increase risk of death due to PTE. Undiagnosed and untreated DVT is often the underlying cause of sudden death due to PTE.
OUR EXPERIENCE IN CARPAL TUNNEL SYNDROME THERAPEUTIC EFFECTIVENESS EVALUATION
Authors: Umure Jolanta , Logina Ināra , Mihailova Marija
Published: October 2019

Objectives: Analyze the literature data on the incidence and manifestation of carpal tunnel syndrome (CTS), as well as the pathogenesis and treatment options. Perform a specially designed, validated test - Pain Detection. Evaluate the objective state of patients with CTS - sensory impairment, compression test. Assess patients’ neurologic and neurophysiologic data before and after the blockade and evaluate its effectiveness. Perform a specially designed, validated test - Patients` Global Impression of Change scale (PGIC) one month after corticosteroid injection (CSI).Methods and Materials: The study includes an analysis of 55 arms of patients of different age with mild and moderate CTS who came for a neurological examination at the Neurology Outpatient Department of the Pauls Stradiņš Clinical University Hospital during the period of 01.08.2018 – 01.01.2019. All patients were analyzed clinically and neurophysiologically before CSI and one month after CSI. A Pain Detect scale, PGIC scale, compression tests and sensory tests were used for the evaluation of clinical symptom. A median nerve sensory and motor nerve conduction study was performed.Results: According to the Pain Detect scale, 60% of patients showed neuropathic pain before CSI, and 78% of patients presented clinical effectiveness after CSI. 98% of patients present clinical effectiveness after CSI in the PGIC scale. 85% of patients had improvement in neurophysiological studies – motor distal latency decreased after CSI. Before CSI, the average motor distal latency was 5.7ms (range 4.5-12.9ms SD±1.5), which was on average 130% from the maximal norm (range 102- 293 SD±36). After the CSI, the average motor distal latency was 5.2ms (range 3.8-10.7ms SD±1.3), which was on average 120% from the maximal norm (range 88-243 SD±30). We didn’t find any significant correlation between the improvement of the patient's clinical condition and the improvement of electrophysiological outcomes.Conclusions: The study concludes that the Pain Detect sensitivity for neuropathic pain evaluation of patients with CTS is 60%. Patients show clinical and neurophysiological improvement after CSI, but there is no correlation between neurophysiological and clinical improvement. The study concludes that the PGIC scale can be used to quickly assess the effectiveness of therapy.
THE USE OF FORENSIC CHEMISTRY METHODS IN THE DETERMINATION OF COUNTERFEIT DRUGS
Authors: Welchinska Elena , Velchynskyi Volodymyr
Published: October 2019

The problem of illegal circulation of drugs, their support and falsification are relevant not only in Ukraine. Experts believe that about 10% of the global medicinal drug market is fake and fraud. Counterfeit drugs may contain the active ingredient with its exact content as well as non-relevant ingredients, may not contain the active ingredient at all or may contain unrefined ingredients. In any case, this leads to a lack of therapeutic effect in the treatment, poisoning and, even, death of patients. As a result of our research, the presence of highly dangerous and toxic components in the composition of drugs (antifreeze, tar, arsenic, mercury and others) was established. In case of poisoning or death of a patient after the use of a counterfeit medicinal drug, an examination is carried out, and the presence of the active and additional ingredients of the drug is confirmed by chemical toxicological analysis. Chemical-toxicological analysis is a part of the science "Forensic chemistry" and allows us to confirm the presence of the drug in the body, the purity of the drug, the presence of the active ingredient of the drug, and therefore allows us to confirm the fact of poisoning or death of a person under the action of a chemical substance (for example, a falsified drug).
HUMAN AS A PHYSIOLOGICAL SOURCE OF DETERIORATION OF THE AIR QUALITY AND COMFORT CONDITIONS INDOORS
Authors: Angelova Radostina A. , Stankov Peter , Markov Detelin , Velichkova Rositsa , Simova Iskra
Published: October 2019

It is imperative a model be developed that can assess the difference between the amount of CO2, generated within the human body and the amount of CO2 that is ejected by the body as a function of indoor air parameters. This model would allow the assessment of the amount of the CO2 which is not ejected by the body through exhalation and which have to be neutralized and ejected by the body through other mechanisms or have to be accumulated in the body depots. Currently, there is no experimental data that allows for predicting the amount of CO2, ejected through the blood gas exchange in the lungs as a function of CO2 concentration in the inhaled air. Our study, conducted within the AIRMEN project, aims to research the phenomenology of the human body as a physiological source of the deterioration of both the indoor environment and conditions of comfort and in particular on the indoor air quality. It is based on an experimental investigation of the external result from the human body metabolism and gas exchange in the lungs. The results of this study make it possible to logically define the limits of the permissible CO2 concentration in the indoor air for the different air quality categories indoors.
IMPACT OF PHYSICAL MUTAGENS ON THE MALE GAMETOPHYTE OF THE TEA PLANT FOR ITS FURTHER USE IN HYBRIDIZATION
Authors: Baratashvili Davit , Lomtatidze Nino , Dumbadze Guguli , Khalvashi Neli , Kedelidze Nino
Published: October 2019

The migration of the radioisotopes - P32 and S35 from the soil to the tea plant (flowers) was studied. It is shown that their accumulation intensity in pollen sacs increases in proportion to the dose and reaches its maximum in the P32 variant after using a 8.0 MBq / ml dose. The migration intensity was the lowest in the 2.0 MBq / ml variant (0.14-0.223 MBq / 100 mg). It is estimated that P32 and S35 have significantly affected the vitality of tea plant pollens through the anomalies of their development. After using 2.0 and 4.0 MBq / ml doses, the vitality of the pollen is reduced in proportion to the dose and the development anomalies increase. Particulalry, the viability of pollen decrease compared to the control group, but the frequency and range of development anomalies increases. These include the slow development of the plant or the acceleration of the development of the primary nucleus, polyspermia, undeveloped pollen tube, etc. The use of processed P32 and S35 tea pollens in hybridization significantly increases the frequency of new formations and results in variability in the domination of signs.  Among the new formations include the induction of haploids and triploids.