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Objective To describe adaptations necessary for effective use of direct-to-consumer (DTC) cameras in an inpatient setting, from the perspective of health care workers. Methods Our qualitative study included semi-structured interviews and focus groups with clinicians, information technology (IT) personnel, and health system leaders affiliated with the Mount Sinai Health System. All participants either worked in a coronavirus disease 2019 (COVID-19) unit with DTC cameras or participated in the camera implementation. Three researchers coded the transcripts independently and met weekly to discuss and resolve discrepancies. Abiding by inductive thematic analysis, coders revised the codebook until they reached saturation. All transcripts were coded in Dedoose using the final codebook. Results Frontline clinical staff, IT personnel, and health system leaders (N  = 39) participated in individual interviews and focus groups in November 2020–April 2021. Our analysis identified 5 areas for effective DTC camera use: technology, patient monitoring, workflows, interpersonal relationships, and infrastructure. Participants described adaptations created to optimize camera use and opportunities for improvement necessary for sustained use. Non-COVID-19 patients tended to decline participation. Discussion Deploying DTC cameras on inpatient units required adaptations in many routine processes. Addressing consent, 2-way communication issues, patient privacy, and messaging about video monitoring could help facilitate a nimble rollout. Implementation and dissemination of inpatient video monitoring using DTC cameras requires input from patients and frontline staff. Conclusions Given the resources and time it takes to implement a usable camera solution, other health systems might benefit from creating task forces to investigate their use before the next crisis. [ABSTRACT FROM AUTHOR]

Background: Research has shown that internet-based cognitive behavioural therapy (iCBT) can be a very promising solution to increase access to and the dissemination of evidence-based treatments to all of the population in need. However, iCBT is still underutilized in clinical contexts, such as primary care. In order to achieve the effective implementation of these protocols, more studies in ecological settings are needed. The Unified Protocol (UP) is a transdiagnostic CBT protocol for the treatment of emotional disorders, which includes depression, anxiety and related disorders, that has shown its efficacy across different contexts and populations. An internet-based UP (iUP) programme has recently been developed as an emerging internet-based treatment for emotional disorders. However, the internet-delivered version of the UP (iUP) has not yet been examined empirically. The current project seeks to analyse the effectiveness of the iUP as a treatment for depression, anxiety and related emotional disorders in a primary care public health setting.Methods: The current study will employ a parallel-group, randomized controlled trial design. Participants will be randomly assigned to (a) the internet-based Unified Protocol (iUP), or (b) enhanced waiting list control (eWLC). Randomization will follow a 2:1 allocation ratio, with sample size calculations suggesting a required sample of 120 (iUP=80; eWLC=40). The Mini-International Neuropsychiatric Interview (M.I.N.I.) will be used for assessing potential participants. The Overall Anxiety Severity and Impairment Scale (OASIS) and the Overall Depression Severity and Impairment Scale (ODSIS) as well as other standardized questionnaires will be used for assessments at baseline, 4 weeks, 8 weeks and 12 weeks from baseline and for the iUP condition during the follow-up.Discussion: Combining the advantages of a transdiagnostic treatment with an online delivery format may have the potential to significantly lower the burden of emotional disorders in public health primary care setting. Anxiety and depression, often comorbid, are the most prevalent psychological disorders in primary care. Because the iUP allows for the treatment of different disorders and comorbidity, this treatment could represent an adequate choice for patients that demand mental health care in a primary care setting.Trial Registration: ISRCTN18056450 https://doi.org/10.1186/ISRCTN18056450 . [ABSTRACT FROM AUTHOR]

Purpose: At diagnosis and throughout the disease course, patients with high-grade glioma (HGG) experience a diminished quality of life (QOL) and increased fatigue. Naltrexone, an orally semisynthetic opiate antagonist, is FDA-approved for the treatment of heroin/alcohol addiction, and low-dose naltrexone (LDN) has been observed to improve QOL and lower fatigue in other neurological illnesses, such as multiple sclerosis. LDN is believed to function as a partial agonist and can lead to shifts in neurochemicals that reduce fatigue. Based on this, we sought to study whether LDN has an impact on QOL and fatigue in patients with HGG. Methods: In a placebo-controlled, double-blind study, we randomized 110 HGG patients to receive placebo (N = 56) or LDN 4.5 mg orally at night (N = 54). Subjects received LDN or placebo at day 1 of concurrent radiation and temozolomide therapy and continued for 16 weeks. Change from baseline in patient-reported outcomes of QOL (Functional Assessment of Cancer Therapy-Brain) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) was assessed. Results: Demographics were WHO grade IV (85%), male (56%), KPS 90–100 (51%), grossly resected (55%), and mean age of 56 years. QOL and fatigue changes between baseline and post concurrent chemotherapy and radiation therapy were not significantly different between patients receiving LDN or placebo. The adverse event profiles for LDN and placebo were similar and attributed to concomitant use of temozolomide. Conclusions: LDN has no effect on QOL and fatigue in HGG patients during concurrent chemotherapy and radiation therapy. Trial registration: United States National Library of Medicine Clinical Trials.gov NCT01303835, Date 2/25/2011. [ABSTRACT FROM AUTHOR]

Background Outpatient clinics treating neuro-oncology patients are becoming more multidisciplinary. Utilization of all team members is critical for the holistic care of these complex patients. Specifically, the role of clinical pharmacist (CP) in the ambulatory clinic remains undefined and will likely evolve as more therapeutics are developed for CNS malignancies. We queried the Society for Neuro-Oncology (SNO) membership about the availability of a CP in their ambulatory setting and, if present, the role of that CP. Methods In an IRB-exempt study, we surveyed the SNO community and analyzed responses to queries about CPs in the ambulatory setting. Results Of the 65 SNO members who responded, 52 were clinical members. Of these 52 clinicians, the majority were physicians (88.5%, n = 46). Of these physicians, most were in academic practices (93.5%, n = 43). Over half of the 52 clinical respondents (51.9%, n = 27) reported that they saw ≥30 primary brain tumor patients per month, thus typifying busy clinics. Despite having busy clinics, only 12 (28.6%) of 42 providers with access to a CP reported that their CP was solely dedicated to neuro-oncology patients. For the respondents who had access to a CP, only ~two-thirds of those CPs had direct patient interaction. The top 3 roles of the CP included medication review, chemotherapy dosing/modifications, and practice guideline development; none of which involve direct patient interaction. Conclusions We found that while our surveyed population of SNO clinical members have demanding outpatient practices, most do not have the support or expertise of dedicated neuro-oncology CPs. [ABSTRACT FROM AUTHOR]

Background: Retrospective analyses of randomized trials suggest that Black men with metastatic castration‐resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. Methods: This race‐stratified, multicenter study estimated radiographic progression‐free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate‐specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome‐wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self‐identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. Results: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. Conclusions: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side‐effect rates than White men. This exploratory genome‐wide analysis of TTP identified a possible candidate marker of ancestry‐dependent treatment outcomes. This is the first prospective, race‐stratified study in advanced prostate cancer demonstrating important trends in outcomes previously only observed in retrospective reports. These results demonstrate the feasibility of this approach in a multicenter setting and establish important preliminary data with regard to differences in toxicity profiles and predictive biomarkers by race. [ABSTRACT FROM AUTHOR]

Background Spirituality can impact patients' attitudes and decisions about treatment and end-of-life care when coping with cancer. Previous studies documented health-related quality of life (HRQoL) and spiritual well-being (SWB) as positively correlated within a general cancer patient population, but little is known about their association in the primary brain tumor population. We sought to measure SWB in primary brain tumor patients and evaluate whether it was associated with HRQoL. Methods Six-hundred and six patients treated at The Preston Robert Tisch Brain Tumor Center at Duke between December 16, 2013 and February 28, 2014 with data in the PRoGREss registry are included in this retrospective analysis. Each patient completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-Sp-12) and -Fatigue (FACIT-F), and the Functional Assessment of Cancer Therapy-General and -Brain (FACT-G and FACT-Br). Results Mean age was 49.1 years (SD = 13.5 years), male (N = 328, 54.1%), married (N = 404, 66.7%), at least college-educated (N = 381, 62.9%), and diagnosed with a high-grade glioma (N = 412, 68.0%). Multiple regression analyses were performed on both the FACT-G and the FACT-Br using the FACIT-Sp-12 sub-scales of Meaning/Peace and Faith, FACIT-F, belief in God or a higher power, prayer, gender, tumor grade, and Karnofsky Performance Status (KPS) as predictors. We found that greater SWB (measured by FACIT-Sp-12) was associated with better HRQoL (measured by FACT-G and FACT-Br; p <.0001). Conclusion The association between reported SWB and reported improved HRQoL emphasizes the importance of spirituality in primary brain tumor patients, suggesting SWB must be considered in strategies to improve HRQoL. [ABSTRACT FROM AUTHOR]

PURPOSE: Androgen receptor splice variant 7 (AR-V7) detection in circulating tumor cells (CTCs) is associated with a low probability of response and short progression-free (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy. PATIENTS AND METHODS: PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy. We assessed AR-V7 status using the Johns Hopkins modified AdnaTest CTC AR-V7 messenger RNA assay and the Epic Sciences CTC nuclear-localized AR-V7 protein assay before treatment. The primary objective was to validate the independent prognostic value of CTC AR-V7 status based on radiographic/clinical PFS. OS, confirmed prostate-specific antigen (PSA), and objective radiologic responses were secondary end points. RESULTS: We enrolled 118 men with mCRPC treated with abiraterone or enzalutamide, 51 of whom received subsequent docetaxel or cabazitaxel. Pretreatment CTC AR-V7 status by the Johns Hopkins and Epic Sciences assays was independently associated with worse PFS (hazard ratio [HR], 1.7; 95% CI, 1.0 to 2.9 and HR, 2.1; 95% CI, 1.0 to 4.4, respectively) and OS (HR, 3.3; 95% CI, 1.7 to 6.3 and HR, 3.0; 95% CI, 1.4 to 6.3, respectively) and a low probability of confirmed PSA responses, ranging from 0% to 11%, during treatment with abiraterone or enzalutamide. At progression, subsequent CTC AR-V7 detection was not associated with an inferior PSA or radiographic response or worse PFS or OS with subsequent taxane chemotherapy after adjusting for CellSearch CTC enumeration and clinical prognostic factors. CONCLUSION: Detection of AR-V7 in CTCs by two different blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, but such men with AR-V7–positive disease still experience clinical benefits from taxane chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated.Methods: One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150-200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL).Results: Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity.Conclusions: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone. [ABSTRACT FROM AUTHOR]

Purpose: Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin's lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of systemic disease. This rare disease accounts for ~ 3% of all primary central nervous system (CNS) tumors. Methotrexate-based regimens are the standard of care for this disease with overall survival rates ranging from 14 to 55 months. Relapse after apparent complete remission can occur. We sought to understand the outcomes of patients who relapsed. Methods: This is an IRB-approved investigation of patients treated at our institution between 12/31/2004 and 10/12/2016. We retrospectively identified all cases of PCNSL as part of a database registry and evaluated these cases for demographic information, absence or presence of relapse, location of relapse, treatment regimens, and median relapse-free survival. Results: This analysis identified 44 patients with a pathologically confirmed diagnosis of PCNSL. Mean age at diagnosis was 63.1 years (range 20–86, SD = 13.2 years). Of the 44 patients, 28 patients successfully completed an initial treatment regimen without recurrence or toxicity that required a change in therapy. Relapse occurred in 11 patients with the location of relapse being in the CNS only (n = 5), vitreous fluid only (n = 1), outside CNS only (n = 3), or a combination of CNS and outside of the CNS (n = 2). Sites of relapse outside of the CNS included testes (n = 1), lung (n = 1), adrenal gland (n = 1), kidney/adrenal gland (n = 1), and retroperitoneum (n = 1). Median relapse-free survival after successful completion of therapy was 6.7 years (95% CI 1.1, 12.6). Conclusion: After successful initial treatment, PCNSL has a propensity to relapse, and this relapse can occur both inside and outside of the CNS. Vigilant monitoring of off-treatment patients with a history of PCNSL is necessary to guide early diagnosis of relapse and to initiate aggressive treatment. [ABSTRACT FROM AUTHOR]

Background: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immune responses through the activation of T cells. However, glioblastoma-induced immune suppression is a major obstacle to an effective and durable immunotoxin-mediated antitumor response. We hypothesized that D2C7-IT-induced immune response could be effectively augmented in combination with αCTLA-4/αPD-1/αPD-L1 therapies in murine models of glioma. Methods: To study this, we overexpressed the D2C7-IT antigen, murine EGFRvIII (dmEGFRvIII), in established glioma lines, CT-2A and SMA560. The reactivity and therapeutic efficacy of D2C7-IT against CT-2A-dmEGFRvIII and SMA560- dmEGFRvIII cells was determined by flow cytometry and in vitro cytotoxicity assays, respectively. Antitumor efficacy of D2C7-IT was examined in immunocompetent, intracranial murine glioma models and the role of T cells was assessed by CD4+ and CD8+ T cell depletion. In vivo efficacy of D2C7-IT/αCTLA-4/αPD-1 monotherapy or D2C7-IT+αCTLA-4/ αPD-1 combination therapy was evaluated in subcutaneous unilateral and bilateral CT-2A-dmEGFRvIII glioma-bearing immunocompetent mice. Further, antitumor efficacy of D2C7-IT+αCTLA-4/αPD-1/αPD-L1/αTim-3/αLag-3/αCD73 combination therapy was evaluated in intracranial CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII glioma-bearing mice. Pairwise differences in survival curves were assessed using the generalized Wilcoxon test. Results: D2C7-IT effectively killed CT-2A-dmEGFRvIII (IC50 = 0.47 ng/mL) and SMA560-dmEGFRvIII (IC50 = 1.05 ng/mL) cells in vitro. Treatment of intracranial CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII tumors with D2C7-IT prolonged survival (P = 0.0188 and P = 0.0057, respectively), which was significantly reduced by the depletion of CD4+ and CD8+ T cells. To augment antitumor immune responses, we combined D2C7-IT with αCTLA-4/αPD-1 in an in vivo subcutaneous CT-2A-dmEGFRvIII model. Tumor-bearing mice exhibited complete tumor regressions (4/10 in D2C7-IT+αCTLA-4 and 5/10 in D2C7-IT+αPD-1 treatment groups), and combination therapy-induced systemic antitumor response was effective against both dmEGFRvIII-positive and dmEGFRvIII-negative CT-2A tumors. In a subcutaneous bilateral CT-2A-dmEGFRvIII model, D2C7-IT+αCTLA-4/αPD-1 combination therapies showed dramatic regression of the treated tumors and measurable regression of untreated tumors. Notably, in CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII intracranial glioma models, D2C7-IT+αPD-1/αPD-L1 combinations improved survival, and in selected cases generated cures and protection against tumor re-challenge. Conclusions: These data support the development of D2C7-IT and immune checkpoint blockade combinations for patients with malignant glioma. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)‐high or mismatch repair‐deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. Methods: We performed a single institution retrospective review of men with metastatic castrate‐resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. Results: We identified 48 men who received ≥1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ≥3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ≥50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ≥90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b, one of whom also had MSH2 loss and was MSI‐H and TMB‐high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression‐free‐survival was 1.8 months (range 0.4‐13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow‐up of 7.1 months. Conclusions: In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 17% (8/48) of men, including a dramatic ≥90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD‐1 inhibitor responsiveness in prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment. Methods: We conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues. Results: We enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC. Conclusions: Osteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy. [ABSTRACT FROM AUTHOR]

Background: In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control.Methods: We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54-60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m(2)/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules.Results: We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67-79 %.Conclusion: Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ. [ABSTRACT FROM AUTHOR]

There are over one million mobile applications or "apps" available for use in improving health. One population that could potentially benefit from the use of mobile applications is the elderly. Choosing appropriate applications can be daunting, however, and there is a paucity of research identifying which applications are useful for elderly patients. The aim of this study is to perform a literature review regarding the available mobile applications for health and fitness and to provide health care providers with evidence-based information about other potentially useful and novel applications for their older patients. In an attempt to address the need for identifying useful mobile applications for the elderly, I conducted a literature review on health and technology articles published within the last ten years. Search terms included mobile app*, smartphone app*, elderly, older, and aged. Eight articles are identified and discussed here that meet the inclusion criteria. Six of these articles reported effectiveness of the application, while all reported positive feedback from elderly users. Two of the studies were randomized controlled trials, and four were pilot or feasibility studies. Three notable apps that received positive feedback--"Its LiFE", "Heart Coach", and "Stim' Art"-- were all supplemented by another form of technology and human interaction. The sample sizes of these studies are small, and knowledge related to the effectiveness of these apps in older adults is limited; therefore, further research is necessary to evaluate the effectiveness of apps in improving the health of all patients. [ABSTRACT FROM AUTHOR]

Primary brain tumor patients experience high levels of distress. The purpose of this cross-sectional, retrospective study is to evaluate the level and different sources of psychosocial distress and how these pertain to health-related quality of life (HRQoL). The Primary and Recurrent Glioma registry at Duke's The Preston Robert Tisch Brain Tumor Center was queried retrospectively for demographic and clinical information on patients seen between December 2013 and February 2014. Data also included the National Comprehensive Cancer Network's Distress Thermometer (NCCN-DT), Functional Assessment of Cancer Therapy-Brain Cancer (FACT-Br), and Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F). 829 subjects completed questionnaires. 54% were male; 96% completed the NCCN-DT; 33.3% had a DT score ≥4 (moderate/severe distress). Women reported DT ≥ 4 more often than men (38.6 vs 29.0%; p = 0.005). Patients within 1 year of diagnosis reported DT ≥ 4 more often than those 1+ years after diagnosis (38.8 vs 30.9%; p = 0.034). 73.0% reported physical problems; the most frequent being fatigue (43.2%) and memory/concentration (40.9%). 42.0% complained of emotional problems with worry (29.4%) and nervousness (22.4%) being the most common. Patients who reported at least one practical, family, emotional or physical problem had significantly lower HRQoL scores (p < 0.001). Primary brain tumor patients experience memory dysfunction, fatigue, nervousness, worry, and financial concerns, which have a negative effect on the patient's HRQoL. By identifying and addressing these stressors, it may be possible to improve patient HRQoL. [ABSTRACT FROM AUTHOR]

Purpose: Given that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan-bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2-5), overall CINV CR (days 1-5), and QoL, fatigue, and toxicity.Materials and Methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL-DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL-DEX dose administrations 1-3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade ≥3 PAL-DEX treatment-related toxicities.Conclusion: Data suggest that PAL-DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma. [ABSTRACT FROM AUTHOR]

In this paper, we present a dynamic algorithm that checks if a single-source embedded digraph is upward planar in the presence of edge insertions and edge deletions without changing the embedding of the digraph. We show that it can be checked in O(log n) amortized time whether the updated graph is a single-source upward planar digraph with a fixed external face. [ABSTRACT FROM AUTHOR]

Regulatory B cells that secrete IL-10 (IL-10 B) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10 B biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10 B responses within this patient population and demonstrate that the IL-10 B compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10 B frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10 B frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10 B. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM. [ABSTRACT FROM AUTHOR]

Automatic layout of tables is useful in word processing applications and is required in online applications because of the need to tailor the layout to viewport width, choice of font, and dynamic content. However, if the table contains text, minimizing the height of the table for a given maximum width is a difficult combinatorial optimization problem because of the need to find the right choice of height/width configuration for each cell in the table. We investigate the modelling decisions involved in formulating this problem for use with standard combinatorial optimization techniques that are guaranteed to find the minimal-height table. To the best of our knowledge, we are the first to do so. We provide a detailed empirical evaluation of the resulting models using mixed integer programming and constraint programming with lazy clause generation. [ABSTRACT FROM AUTHOR]

Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may represent objective markers of post-operative survival (Progression Free and Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from patients aged 22 years or less were studied. The original histologic grade was recorded, H&E sections were reviewed for vascular proliferation status, and immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank = 0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX ≤ 5 % total area localization were alive at last follow-up. Perinecrotic CA IX staining was also associated with vascular proliferation (p = 0.006), though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI 1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and MIB-1 expression are predictive biomarkers for survival in children with posterior fossa ependymomas. These markers represent objective indicators of survival that supplement H&E grading alone. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression. [ABSTRACT FROM AUTHOR]

The author analyzes the written work of philosopher Henri Bergson on the writings of Roman philosopher and poet Titus Carus Lucretius. It is stated that, by studying the philosophical past Bergson went on to become the event of his own thinking. It is stated that, Bergson starts his writing on Lucretius by highlighting the fact that very little is known about the surroundings and environment in which Lucretius lived.

Background: Chemotherapy-associated neutropenia has been reported to be a pharmacodynamic marker of response in some advanced solid tumors. Factors that accelerate drug clearance lead to lower plasma concentrations and toxicity, including neutropenia. Smoking accelerates the metabolism of several drugs, including chemotherapy. We sought to study the effects of smoking on gemcitabine-induced neutropenia in this retrospective study. Methods: Smoking status and neutropenia along with other clinical parameters were recorded in 151 patients receiving first-line gemcitabine-based chemotherapy for advanced solid tumors. Results: Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary (70.9%), or other/unknown primary cancer (15.2%). Logistic regression showed that never smokers had increased neutropenia versus current smokers (odds ratio: 3.5; 95% confidence interval, CI: 1.1-11.4). A 5-unit increase in pack-years reduced the odds of having higher neutropenia toxicity by 6.3% (95% CI 12 to 1%; p = 0.036). Conclusion: Smokers had less neutropenia than nonsmokers, a finding that was more pronounced with increasing pack-years. This pharmacodynamic marker of gemcitabine-induced neutropenia may result in less efficacy of gemcitabine. Future prospective trials should correlate smoking, metabolizing phenotype, neutropenia, and response to gemcitabine therapy. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L ( n = 150) were reviewed to quantify the lobular component (≤20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade ( p < 0.001), be positive for estrogen receptor (96 vs. 70 %; p < 0.0001) and progesterone receptor (84 vs. 57 %; p < 0.0001), and less likely to overexpress HER-2/neu (12 vs. 23 %; p = 0.001). Despite these favorable prognostic features, IDC-L had a higher frequency of nodal metastases (51 vs. 34 %; p < 0.0001) and a worse 5-year disease-free survival than IDC (hazard ratio = 0.454; p = 0.0004). ILC and IDC-L had similar clinicopathologic features and outcomes. The proportion of the lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC. [ABSTRACT FROM AUTHOR]

We show how to compute a maximum upward planar single-source subgraph of a single-source embedded DAG G. We first show that finding a maximum upward planar subgraph of a single-source embedded digraph is NP-complete. We then give a new characterization of upward planar single-source digraphs. We use this characterization to present an algorithm that computes a maximum upward planar single-source subgraph of a single-source embedded DAG. This algorithm takes O( n) time in the worst case and O( n) time on average. [ABSTRACT FROM AUTHOR]