bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polypharmacy and medication costs at end of life among commercially insured adults age 65 and older with cancer.
Authors: McDermott Cara L. , Fedorenko Catherine R. , Sun Qin , Curtis J. Randall , Kreizenbeck Karma L. , Conklin Ted , Smith Bruce , Lyman Gary H. , Ramsey Scott David 
Published: November 2018

65 Background: Polypharmacy, or the concurrent use of multiple medications, may expose patients to drug-drug interactions and excessive costs. There are limited data on polypharmacy for commercially insured older adults, primarily Medicare Advantage patients, that may have better access to medication management services than Medicare fee-for-service patients. We characterized medication use and out-of-pocket (OOP) medication costs in the last month of life among patients age 65+ who did not enroll in hospice to examine medication use in this population. Methods: We linked enrollment and claims records from two regional commercial insurers to Surveillance, Epidemiology, and End Results (SEER) Cancer Surveillance System and Washington State Cancer Registry records for patients diagnosed with a stage IV malignancy in Washington State between January 1, 2007-December 31, 2016. We calculated OOP costs as the difference between allowed and paid claim amounts and adjusted OOP costs (aOOP) for inflation to 2017 dollars. Results: Among 345 patients with medication claims in their last month, 156 (45%) had a chemotherapy claim. Average age was 74 years (range 65-95), 55% (n = 190) were male, and 150 had lung cancer (44%). Patients averaged 7.7 medication claims (range 1-50); 151 (44%) had 1-4, 99 (29%) had 5-9, and 95 (27%) had 10+. Common symptom-related medications were opioids, benzodiazepines, anti-emetics. Chemotherapy was associated with higher odds of 10+ prescriptions (OR 1.38, 95% CI 1.26-1.51). Excluding four patients with aOOP chemotherapy costs > $14,000, average aOOP costs were $101 for chemotherapy claims (range $0-$8957) and $33 for non-chemotherapy claims ($0-$1993). Costs for those in the highest quartile ranged from $320-$8957 for chemotherapy claims and $100-1993 for non-chemotherapy claims. Conclusions: Most subjects had at least five medication claims in their last 30 days. One-quarter had 10+ claims, which was associated with chemotherapy receipt. Hospice enrollment could reduce OOP costs, as hospice provides symptom-related medications. Interventions facilitating hospice enrollment and reducing chemotherapy use may minimize polypharmacy and cost burden for patients and families.
Factors associated with receipt of palliative-only care among survivors with head and neck cancer.
Authors: Osazuwa-Peters Nosayaba , Bukatko Aleksandr R , Simpson Matthew C , Gaubatz Matthew , Polednik Katherine M. , Adjei Boakye Eric 
Published: November 2018

73 Background: Head and neck cancer (HNC) survivors with end-stage disease may receive multimodal treatment with non-curative intent. However, besides clinical indications for palliative care, there is a paucity of data describing nonclinical factors associated with receipt of palliative care. This study aimed at characterizing sociodemographic factors associated with HNC survivors receiving palliative-only care. Methods: We used data from the National Cancer Database from 2004-2014, restricting our cohort to adult HNC survivors receiving palliative-only care. Multivariate logistic regression estimated association between sociodemographic factors and receiving palliative-only care. Survival of palliative-only patients was assessed via Cox proportional hazards model. Final regression models were adjusted for clinical/nonclinical covariates, including: age, comorbidity score, tumor site, cancer stage, histology, HPV status, and population density/urbanization. Results: Out of 325,489 HNC survivors, 2,404 received palliative-only treatment. Mean age was 69.1 years, and median survival was 4.9 months. Sociodemographic factors associated with receiving palliative-only care were gender: (female aOR=1.11; 95% CI 1.02, 1.22), race/ethnicity: [(Hispanic aOR=0.77; 95% CI 0.62, 0.97), (Non-Hispanic Black aOR=1.35; 95% CI 1.20, 1.52)], insurance status: [(uninsured aOR=2.59; 95% CI 2.13, 3.14), (Medicaid aOR=3.11; 95% CI 2.67, 3.61), (Medicare aOR=1.71; 95% CI 1.50, 1.95)], travel distance for care: (≥50 miles aOR=0.64; 95% CI 0.55, 0.74). Additionally, survivors receiving palliative-only care who were uninsured (aHR=1.34; 95% CI 1.08, 1.65), under Medicaid (aHR=1.29; 95%CI 1.10, 1.52), or Medicare (aHR=1.16; 95%CI 1.01, 1.33) were significantly more likely to die compared with those privately insured. Conclusions: Females, blacks, and those uninsured, under Medicaid/Medicare disproportionately contribute to the palliative-only population among HNC survivors. Disparities persist even at end-stage disease among HNC survivors and impact disease outcome.
A single-center randomized clinical trial of palliative rehabilitation versus standard care alone in patients with newly diagnosed non-resectable cancer.
Authors: Nottelmann Lise , Groenvold Mogens , Petersen Morten Aagard , Vejlgaard Tove , Jensen Lars Henrik 
Published: November 2018

75 Background: Palliative care and rehabilitation may both improve quality of life, but research on their combination and early integration into oncology care is sparse. Methods: Adults diagnosed with non-resectable cancers within the last 8 weeks were randomized to standard oncology care alone or an additional offer of individually tailored palliative rehabilitation. Two mandatory consultations and a 12 week open contact with a specialized palliative care team were offered. An additional opportunity was participation in a multidisciplinary group program combining a patient/caregiver school with physical exercise, individual consultations, or both. Participants were assessed at baseline and after 6 and 12 weeks with an extended version of the EORTC QLQ-C30 questionnaire using the item banks for computer-adaptive testing to obtain improved measurement. At baseline participants were asked to choose what they needed help with the most from a list of possible 'primary problems' corresponding to 12 of the 15 QLQ-C30 scales. The primary outcome was the change in that "primary problem" scale measured as area under the curve across the 12 weeks. Group differences were tested in an adjusted linear regression model. Results: 301 patients with lung- (40%), gastrointestinal- (27%), prostatic- (18%), and various other solid tumors (15%) were included. 139 patients were allocated to the intervention group and 149 to the standard care group. The palliative rehabilitation intervention was received by 132. Of those, 26 received the two mandatory consultations only, 59 additionally participated in a group program, and 47 additionally received individual consultations without participation in a group. The intervention showed an effect for the primary outcome with an absolute between-group difference of 3.0 (0.0;6.0) p = 0.047. The result was confirmed by a sensitivity analysis of the change from baseline to 12 weeks showing an absolute difference of 3.3 (1.0; 5.6) p = 0.005. Conclusions: A palliative rehabilitation intervention initiated soon after diagnosis and integrated in the standard oncology treatment improved quality of life. Clinical trial information: NCT02332317.
A randomized controlled trial of a novel artificial-intelligence based smartphone application to optimize the management of cancer-related pain.
Authors: Kamdar Mihir M. , Centi Amanda Jayne , Fischer Nils , Jethwani Kamal 
Published: November 2018

76 Background: Cancer pain affects 70-90% of advanced malignancy patients, resulting in impaired quality of life and increased healthcare utilization. Novel care delivery models are needed to optimize care for patients dealing with cancer-related pain in between clinic visits. ePAL is a smartphone application(app) that regularly monitors pain and uses artificial intelligence(AI) to differentiate urgent from non-urgent issues to intercede in real time. The purpose of this randomized controlled trial was to determine ePAL's impact on pain severity, attitudes toward cancer treatment, and healthcare utilization in patients with cancer pain. Methods: MGH Palliative Care Clinic Patients with pain from metastatic, solid-organ cancer (n=112) were recruited and randomized to either a control group (n=56) that received usual care or an intervention group (n=56) that used the ePAL app in addition to usual care for 8 weeks. The app assessed pain 3 times/week and questionnaires about pain (BPI), attitudes towards cancer treatment(BQ-II), and general anxiety(GAD-7) were given at 0, 4, and 8 weeks. A repeated measures mixed model approach assessed how outcome measures changed over time. Models controlled for baseline differences at enrollment and random slopes in addition to baseline depression score, age and sex(alpha=0.05). Results: Pain severity (BPI) and negative attitudes toward cancer pain treatment (BQ-II) decreased significantly for those using the app compared to controls(coeff. -0.09, 95% CI: -0.17, -0.007, p=0.034 and coeff. -0.037, 95% CI: -0.072, -0.001, p=0.042 respectively). Anxiety scores increased for those using ePAL compared to controls (coeff. 0.21, 95% CI: 0.039, 0.37, p=0.015). Over 8-weeks, ePAL users had 40% fewer inpatient hospital admissions compared to controls (n=15 vs. n=25, p=0.048). Conclusions: To our knowledge, this is the first mobile app to utilize AI and clinical algorithms to significantly decrease pain and reduce overall inpatient hospitalizations in patients with cancer-related pain. Clinical trial information: NCT02069743.
Palliative radiotherapy education in hospice and palliative medicine fellowship: A national needs assessment.
Authors: Martin Emily Jean , Jones Joshua Adam 
Published: November 2018

87 Background: Educational deficiencies among hospice and palliative medicine (HPM) physicians are thought to contribute to sub-optimal utilization of palliative radiotherapy (PRT) for patients with advanced cancer. We conducted a national survey of HPM fellowship program directors and fellows to assess the need for increased PRT education in HPM fellowship. Methods: A 17-item, anonymous, electronic survey was distributed via email in May 2018 to the directors of all US Accreditation Council for Graduate Medical Education-accredited HPM fellowship programs with at least one enrolled fellow. A similar 19-item survey was emailed to the coordinators of these programs for distribution to enrolled fellows. Three reminder emails were sent over a one-month period. Results: Eighty-one (68%) of 120 eligible program directors and 114 (34%) of 338 eligible fellows completed the surveys. Nearly all respondents (98% of program directors and 99% of fellows) agreed that HPM physicians should be familiar with the principles of PRT and 95% of both groups agreed that this topic should be taught in HPM fellowship. Thirty percent of programs, however, lacked any PRT curriculum and 57% of programs provided only 1 or 2 hours of didactic PRT education. The minority of fellows felt confident in their ability to identify radiation oncology emergencies (43%) or to manage symptoms associated with radiotherapy toxicities (42%) and only 56% felt confident in their ability to assess which patients should be referred to radiation oncology for possible PRT. Notably, the majority of fellows reported that if they were more knowledgeable about PRT they would be more likely to consider referral to radiation oncology (78%), to collaborate with the radiation oncologists involved in their patients’ care (76%), and to advocate for shorter fractionation schedules or possible omission of radiation therapy altogether based on a patient’s prognosis or goals of care (78%). Conclusions: HPM fellowship program directors and fellows agree that that there is a need for increased education in PRT in HPM fellowship. Curricular interventions that address this need may result in more appropriate utilization of PRT.
Disentangled: A single institutional analysis comparing differences in end-of-life patterns and resource utilization in acute leukemia and bone marrow transplant units.
Authors: Decastro Gene , Anandan Samuel , Ginsberg Adam , Lopez Santiago 
Published: November 2018

90 Background: The impact of palliative medicine in patients with hematologic malignancies is a growing area of investigation. Over the last year, the Palliative Medicine service at North Shore University Hospital (NSUH) has developed and sustained a co-management model for patients admitted to the acute leukemia (ALU) or bone marrow transplant (BMTU) units. Methods: The primary outcome measure was the time from admission to initial consult. The secondary outcome measure was length of stay in a goal concordant setting to receive end of life (EOL) care, namely our inpatient palliative care unit (PCU). Results: There were 106 new consults in twelve months (45 acute leukemia/lymphoma consults and 61 bone marrow transplant consults). The principal diagnosis seen on the ALU was acute myeloid leukemia (56%), whereas on the BMTU it was multiple myeloma (28%). The average time to consult for the ALU decreased from 18.8 days at 6 months to 8.8 days at 12 months. For the BMTU, time to consult decreased from 10.2 days at 6 months to 4.6 days at 12 months. The mortality rate of patients seen from the ALU and BMTU was 40% and 12%, respectively. Of the ALU population deaths, 83% were 65 or older, compared to 29% of the BMTU deaths. Mortality events in the ICU were greater for BMTU patients (43%) relative to ALU patients (11%). Fifty percent of the ALU inpatient expirations were able to receive EOL care in our PCU. The remaining deaths were in the ALU (39%) or ICU (11%). For BMT patients, 57% died on the BMTU, and 43% in the MICU. Despite comparable numbers of PCU transfers during the pre- and post-intervention period, our initiative increased the average LOS in the PCU from 1.1 to 5.7 days. Of the ALU patients electing DNR prior to death (83%), the average DNR-to-death days was 10.6 days, whereas BMTU patients who elected DNR prior to death (50%) had an average of 6.5 DNR-to-death days. Conclusions: This partnership allowed for recognition of differences in EOL care patterns across these populations. It has demonstrated a benefit by accelerating time to consult and enhancing transitions to goal concordant settings for patients with hematologic malignancies at the end of their lives.
Emergent palliative radiotherapy: Dedicated personnel resources to improve workflow.
Authors: Wu Susan Y. , Boreta Lauren , Chan Jason , Chapman Christopher H. , Yee Emily , Braunstein Steve E. 
Published: November 2018

93 Background: Approximately half of patients undergoing radiotherapy (RT) do so with palliative intent. Urgent indications for RT may include neurologic compromise, pain, or bleeding. While some practices have a dedicated palliative RT team, the majority utilize an “on-call” system with a rotating outpatient radiation oncologist. We report our experience with a dedicated nurse practitioner (NP) to assist with palliative RT workflow, with the goal of expediting patient care. Methods: 226 inpatients treated with RT to a site of metastatic disease from May 2012 to May 2018 were included. Since August 2017, an NP has helped expedite emergent RT referrals. Mann-Whitney U tests were used to compare days between steps in the treatment planning process before and after integration of an NP. Results: The median age at RT was 60 years (IQR 49–69). The most common primary sites were lung (26%) and breast (12%). The most common indication for RT was symptomatic brain metastases (SBM, 33% of patients), followed by pain (27%) and spinal cord compression or cauda equina syndrome (SCC) (21%). The median time from referral (defined as initial contact by the primary team) to consultation was one day (IQR 0-2), and from referral to RT was four days (IQR 2-6). Median time from referral to RT was shorter for SCC (two days, IQR 1-4.5) and SBM (three days, IQR 1–6), than pain (five days, IQR 2–8) (p = 0.001 and p = 0.015, respectively). 68% of patients with SCC (32/47) and 35% of patients with SBM (26/74) started RT within one day of consultation. With an NP, patients were more likely to undergo simulation (sim) the same day as consultation (74% vs. 58%, p = 0.03). Same day sim was more common in patients with neurologic deficits (SCC+SBM) than those without (87% vs. 62%, p = 0.02). In those with neurologic deficits, time from consultation to sim decreased from 0.85 to 0.23 days (p = 0.04) and time from sim to RT decreased from 2.7 to 1.8 days (approaching significance, p = 0.06). In patients treated for pain, time from consultation to RT was reduced from 6.3 to 2.1 days (p = 0.02). Conclusions: For practices without a dedicated palliative RT team, involvement of an NP can improve workflow and expedite urgent RT. Further research is needed to rigorously explore quality improvement in the delivery of palliative RT.
Integration and delivery of palliative and supportive care.
Authors: Okinyi Fredrick Otieno , Dower Joshua , Serubuga Makory Germaine , Orndorff Christy , Gallegos Jarred , Indalo Edwin , Musau Helena , Adhiambo Catharine , Wangechi Catherine , Rochford Rosemary , Sirengo Brigid , Remick Scot C. , Mwanda Walter 
Published: November 2018

97 Background: Pediatric palliative care (PC) and end-of-life (EoL) planning and support for children, families, and providers are under-developed in Kenya. PC providers in Kenya want to build advocacy and teams to support children with life-threatening or limiting diseases and their families. Methods: KEHPCA in collaboration with UoN/KNH and US pediatric PC providers solicited applications from across the country to participate in a weeklong “train-the-trainer” workshop. The program was entirely devoted to pediatric PC and EoL care and is the “first-like” workshop to our knowledge. The program incorporated a variety of teaching and training tools that were used to support children, their families and caregivers suitable for the Kenyan setting. The cases of 7 children (7 mos. to 11 yrs) served as the focal point for training including extensive role-play scenarios. Results: The workshop convened 9-13th July 2018 in Nairobi. KEHPCA selected 31 providers from among 130 across Kenya to participate and included medical officers, nurses, pharmacists, psychosocial workers, spiritual care, and a school teacher. Expectations were identified by participants at the start, pre- and post-conference surveys were completed, and the identical survey was submitted twice to more than 5,000 physicians listed in the Kenya Board of Medicine directory. There is a lack of awareness of the importance of PC by physicians listed in the directory responding to the same survey. The workshop was well received and ways forward identified. Conclusions: There is consensus among participants that there are five critical gaps in pediatric PC in Kenya: 1) PC requires an interdisciplinary team; 2) interdisciplinary family visits are seldom done; 3) there is a need to facilitate EoL and serious illness conversations with families/guardians and children as appropriate (adolescents in particular); 4) identify ways to support the legacy of infants and young children who pass away; and 5) a clear desire to support the healthcare team. These observations will form a solid departure point for developing programs and ways forward for Kenyan children with life-threatening illnesses. [Supported in part by: KEHPCA and NIH grant nos.: D43 TW009333.]
A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I− Symporter
Authors: Martín Mariano , Modenutti Carlos Pablo , Peyret Victoria , Geysels Romina Celeste , Darrouzet Elisabeth , Pourcher Thierry , Masini-Repiso Ana María , Martí Marcelo Adrián , Carrasco Nancy , Nicola Juan Pablo 
Published: November 2018

Abstract
The Na+/iodide (I−) symporter (NIS), a glycoprotein expressed at the basolateral plasma membrane of thyroid follicular cells, mediates I− accumulation for thyroid hormonogenesis and radioiodide therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit lower I− transport than normal thyroid tissue (or even undetectable I− transport). Paradoxically, the majority of differentiated thyroid cancers show intracellular NIS expression, suggesting abnormal targeting to the plasma membrane. Therefore, a thorough understanding of the mechanisms that regulate NIS plasma membrane transport would have multiple implications for radioiodide therapy. In this study, we show that the intracellularly facing carboxy-terminus of NIS is required for the transport of the protein to the plasma membrane. Moreover, the carboxy-terminus contains dominant basolateral information. Using internal deletions and site-directed mutagenesis at the carboxy-terminus, we identified a highly conserved monoleucine-based sorting motif that determines NIS basolateral expression. Furthermore, in clathrin adaptor protein (AP)-1B–deficient cells, NIS sorting to the basolateral plasma membrane is compromised, causing the protein to also be expressed at the apical plasma membrane. Computer simulations suggest that the AP-1B subunit σ1 recognizes the monoleucine-based sorting motif in NIS carboxy-terminus. Although the mechanisms by which NIS is intracellularly retained in thyroid cancer remain elusive, our findings may open up avenues for identifying molecular targets that can be used to treat radioiodide-refractory thyroid tumors that express NIS intracellularly.
Ovulation: Parallels With Inflammatory Processes
Authors: Duffy Diane M , Ko CheMyong , Jo Misung , Brannstrom Mats , Curry Thomas E 
Published: November 2018

AbstractThe midcycle surge of LH sets in motion interconnected networks of signaling cascades to bring about rupture of the follicle and release of the oocyte during ovulation. Many mediators of these LH-induced signaling cascades are associated with inflammation, leading to the postulate that ovulation is similar to an inflammatory response. First responders to the LH surge are granulosa and theca cells, which produce steroids, prostaglandins, chemokines, and cytokines, which are also mediators of inflammatory processes. These mediators, in turn, activate both nonimmune ovarian cells as well as resident immune cells within the ovary; additional immune cells are also attracted to the ovary. Collectively, these cells regulate proteolytic pathways to reorganize the follicular stroma, disrupt the granulosa cell basal lamina, and facilitate invasion of vascular endothelial cells. LH-induced mediators initiate cumulus expansion and cumulus oocyte complex detachment, whereas the follicular apex undergoes extensive extracellular matrix remodeling and a loss of the surface epithelium. The remainder of the follicle undergoes rapid angiogenesis and functional differentiation of granulosa and theca cells. Ultimately, these functional and structural changes culminate in follicular rupture and oocyte release. Throughout the ovulatory process, the importance of inflammatory responses is highlighted by the commonalities and similarities between many of these events associated with ovulation and inflammation. However, ovulation includes processes that are distinct from inflammation, such as regulation of steroid action, oocyte maturation, and the eventual release of the oocyte. This review focuses on the commonalities between inflammatory responses and the process of ovulation.