Men Are at Higher Risk of Screening Positive for Vascular Cognitive Impairment Compared to Women after Stroke and Transient Ischemic Attack.

While women have greater incidence of dementia, men have higher prevalence of vascular risk factors. This study examined sex differences in risk of screening positive for cognitive impairment after stroke. Ischemic stroke/TIA patients (N = 5969) participated in this prospective, multi-centered study, which screened for cognitive impairment using a validated brief screen. Men showed a higher risk of screening positive for cognitive impairment after adjusting for age, education, stroke severity, and vascular risk factors, suggesting that other factors may be contributing to increased risk among men (OR = 1.34, CI 95% [1.16, 1.55], p < 0.001). The effect of sex on cognitive impairment after stroke warrants further attention.

Language discordance as a marker of disparities in cerebrovascular risk and stroke outcomes: A multi-center Canadian study.

Background: Differences in ischemic stroke outcomes occur in those with limited English proficiency. These health disparities might arise when a patient's spoken language is discordant from the primary language utilized by the health system. Language concordance is an understudied concept. We examined whether language concordance is associated with differences in vascular risk or post-stroke functional outcomes, depression, obstructive sleep apnea and cognitive impairment. Methods: This was a multi-center observational cross-sectional cohort study. Patients with ischemic stroke/transient ischemic attack (TIA) were consecutively recruited across eight regional stroke centers in Ontario, Canada (2012 - 2018). Participants were language concordant (LC) if they spoke English as their native language, ESL if they used English as a second language, or language discordant (LD) if non-English speaking and requiring translation. Results: 8156 screened patients. 6,556 met inclusion criteria: 5067 LC, 1207 ESL and 282 LD. Compared to LC patients: (i) ESL had increased odds of diabetes (OR = 1.28, p = 0.002), dyslipidemia (OR = 1.20, p = 0.007), and hypertension (OR = 1.37, p<0.001) (ii) LD speaking patients had an increased odds of having dyslipidemia (OR = 1.35, p = 0.034), hypertension (OR = 1.37, p<0.001), and worse functional outcome (OR = 1.66, p<0.0001). ESL (OR = 1.88, p<0.0001) and LD (OR = 1.71, p<0.0001) patients were more likely to have lower cognitive scores. No associations were noted with obstructive sleep apnea (OSA) or depression. Conclusions: Measuring language concordance in stroke/TIA reveals differences in neurovascular risk and functional outcome among patients with limited proficiency in the primary language of their health system. Lower cognitive scores must be interpreted with caution as they may be influenced by translation and/or greater vascular risk. Language concordance is a simple, readily available marker to identify those at risk of worse functional outcome. Stroke systems and practitioners must now study why these differences exist and devise adaptive care models, treatments and education strategies to mitigate barriers influenced by language discordance.

KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction.

Progression of virtually all forms of chronic kidney disease (CKD) is associated with activation of pro-inflammatory and pro-fibrotic signaling pathways. Despite extensive research, progress in identifying therapeutic targets to arrest or slow progression of CKD has been limited by incomplete understanding of basic mechanisms underlying renal inflammation and fibrosis in CKD. Recent studies have identified Kruppel-like transcription factors that have been shown to play critical roles in renal development, homeostasis, and response to injury. Although KLF11 deficiency has been shown to increase collagen production in vitro and tissue fibrosis in other organs, no previous study has linked KLF11 to the development of CKD. We sought to test the hypothesis that KLF11 deficiency promotes CKD through upregulation of pro-inflammatory and pro-fibrogenic signaling pathways in murine unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis. We found that KLF11-deficiency exacerbates renal injury in the UUO model through activation of the TGF-ß/SMAD signaling pathway and through activation of several pro-inflammatory chemokine signaling pathways. Based on these considerations, we conclude that agents increase KLF11 expression may provide novel therapeutic targets to slow the progression of CKD.

Symptoms of depression and cognitive impairment in young adults after stroke/transient ischemic attack.

Depression and cognitive complaints are common after stroke; these issues have been studied in older populations, but not in the young. Two hundred and seventy four eligible stroke and TIA patients consented to participate and complete the Center for Epidemiologic Studies Depression Scale, and National Institute of Neurological Disorders and Stroke - Canadian Stroke Network 30-min neuropsychological battery; 57 (21%) were ≤ 50 years of age. Younger patients reported greater symptoms of depression and less executive dysfunction than older patients. This study highlights age differences in post-stroke depression symptoms and cognitive impairment, and emphasizes the need for screening across ages.

The Role of Apathy and Depression on Verbal Learning and Memory Performance After Stroke.

OBJECTIVE: Psychiatric symptoms, including depression and apathy, may significantly impede functional and cognitive capabilities following a cerebrovascular event. This study examined the role of apathy and depression on learning and memory performance in stroke patients. METHOD: Stroke patients (n = 140 [119 ischemic, 21 hemorrhagic], mean age = 60.6 [SD = 15.1]) completed the Apathy Evaluation Scale (AES), the Center for Epidemiologic Studies Depression Scale (CES-D), and the California Verbal Learning Test-Second Edition (CVLT-II). RESULTS: Using a 2 × 2 MANOVA with depression (CESD ≥ 16) and apathy (AES ≥ 34) as the independent variables and cognitive performance (i.e., verbal acquisition, short-term free recall, and long-term free recall) as the dependent variables, we found a main effect for apathy (F[3,134] = 2.98, p = .034), such that apathetic stroke patients (n = 24) performed significantly worse on verbal acquisition (F[1,136] = 6.44; p = .012), short-term free recall (F[1,136] = 7.86; p = .006), and long-term free recall (F[1,136] = 8.37; p = .004) than nonapathetic stroke patients (n = 116). There was no main effect of depression on cognitive performance (F[1,136] = 1.72, p = .155). CONCLUSIONS: These results suggest that apathy, not depression, is related to verbal memory performance in stroke patients. Future research should explore whether treatment of apathy (e.g., improving motivation) could be a novel target for improving cognition after stroke. Researchers should also examine whether this model can be applied to other aspects of cognition, including executive function and other areas of memory including autobiographical and working memory.

Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension.

Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.

Apathy, not depressive symptoms, as a predictor of semantic and phonemic fluency task performance in stroke and transient ischemic attack.

OBJECTIVES: This study examined the relationship between apathy and cognition in patients with cerebrovascular disease. Apathy may result from damage to frontal subcortical circuits causing dysexecutive syndromes, but apathy is also related to depression. We assessed the ability of apathy to predict phonemic fluency and semantic fluency performance after controlling for depressive symptoms in 282 individuals with stroke and/or transient ischemic attack. METHOD: Participants (N = 282) completed the Phonemic Fluency Test, Semantic Fluency Test, Center for Epidemiologic Studies Depression Scale, and Apathy Evaluation Scale. A cross-sectional correlational design was utilized. RESULTS: Using hierarchical linear regressions, apathy scores significantly predicted semantic fluency performance (ß = -.159, p = .020), but not phonemic fluency performance (ß = -.112, p = .129) after scaling scores by age and years of education and controlling for depressive symptoms. Depressive symptoms entered into the first step of both hierarchical linear regressions did not predict semantic fluency (ß = -.035, p = .554) or phonemic fluency (ß = -.081, p = .173). Apathy and depressive symptoms were moderately correlated, r(280) = .58, p < .001. CONCLUSIONS: The results of this study are consistent with research supporting a differentiation between phonemic and semantic fluency tasks, whereby phonemic fluency tasks primarily involve frontal regions, and semantic fluency tasks involve recruitment of more extended networks. The results also highlight a distinction between apathy and depressive symptoms and suggest that apathy may be a more reliable predictor of cognitive deficits than measures of mood in individuals with cerebrovascular disease. Apathy may also be more related to cognition due to overlapping motivational and cognitive frontal subcortical circuitry. Future research should explore whether treatments for apathy could be a novel target for improving cognitive outcomes after stroke.

Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-ß signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

The "DOC" screen: Feasible and valid screening for depression, Obstructive Sleep Apnea (OSA) and cognitive impairment in stroke prevention clinics.

BACKGROUND: Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment ("DOC") are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool ("DOC" screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment. METHODS: All consecutive new referrals to a regional Stroke Prevention Clinic who were English-speaking and non-aphasic were eligible to be screened. Time for screen completion was logged. DOC screen results were compared to the neuropsychological battery and polysomnogram assessments using a modified receiver operator characteristic and area under the curve analysis. Data is reported to conform to STARD guidelines. FINDINGS: 1503 people were screened over 2 years. 89% of eligible patients completed the screen in 5 minutes or less (mean 4.2 minutes), less than half the time it takes to complete the Montreal Cognitive Assessment (MoCA). 437 people consented to detailed testing. Of those, 421 completed the Structured Clinical Interview for Depression within 3 months of screening, 387 completed detailed neuropsychological testing within 3 months, and 88 had overnight polysomnograms. Screening scores combined with demographic variables (age, sex, education, body mass index), had excellent validity compared to gold standard diagnoses: DOC-Mood AUC 0.90; DOC-Apnea AUC 0.80; DOC-Cog AUC 0.81. DOC screen scores can reliably categorize patients in to low-, intermediate- or high-risk groups for further action and can do so with comparable accuracy to more time-consuming screens. CONCLUSIONS: Systematic screening of depression, obstructive sleep apnea, and cognitive impairment in 5 minutes or less is feasible and valid in a high volume stroke clinic using the DOC screen. The DOC screen may facilitate improved identification and treatment of these comorbidities to improve function in patients after stroke and in those with other neurological diseases that share these comorbid conditions (e.g. Alzheimer's disease/mild cognitive impairment, Parkinson's disease, Traumatic Brain Injury, multiple sclerosis).

Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress.

Thermal ablative therapies are important treatment options in the multidisciplinary care of patients with hepatocellular carcinoma (HCC), but lesions larger than 2-3 cm are plagued with high local recurrence rates and overall survival of these patients remains poor. Currently no adjuvant therapies exist to prevent local HCC recurrence in patients undergoing thermal ablation. The molecular mechanisms mediating HCC resistance to thermal ablation induced heat stress and local recurrence remain unclear. Here we demonstrate that the HCC cells with a poor prognostic hepatic stem cell subtype (Subtype HS) are more resistant to heat stress than HCC cells with a better prognostic hepatocyte subtype (Subtype HC). Moreover, sublethal heat stress rapidly induces phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dependent-protein kinase B (AKT) survival signaling in HCC cells in vitro and at the tumor ablation margin in vivo. Conversely, inhibition of PI3K/mTOR complex 2 (mTORC2)-dependent AKT phosphorylation or direct inhibition of AKT function both enhance HCC cell killing and decrease HCC cell survival to sublethal heat stress in both poor and better prognostic HCC subtypes while mTOR complex 1 (mTORC1)-inhibition has no impact. Finally, we showed that AKT isoforms 1, 2 and 3 are differentially upregulated in primary human HCCs and that overexpression of AKT correlates with worse tumor biology and pathologic features (AKT3) and prognosis (AKT1). Together these findings define a novel molecular mechanism whereby heat stress induces PI3K/mTORC2-dependent AKT survival signaling in HCC cells and provide a mechanistic rationale for adjuvant AKT inhibition in combination with thermal ablation as a strategy to enhance HCC cell killing and prevent local recurrence, particularly at the ablation margin.

Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening.

Stroke can cause neurological impairment ranging from mild to severe, but the impact of stroke extends beyond the initial brain injury to include a complex interplay of devastating comorbidities including: post-stroke depression, obstructive sleep apnea, and cognitive impairment ("DOC"). We reviewed the frequency, impact, and treatment options for each DOC condition. We then used the Ottawa Model of Research Use to examine gaps in care, understand the barriers to knowledge translation, identification, and addressing these important post-stroke comorbidities. Each of the DOC conditions is common and result in poorer recovery, greater functional impairment, increased stroke recurrence and mortality, even after accounting for traditional vascular risk factors. Despite the strong relationships between DOC comorbidities and these negative outcomes as well as recommendations for screening based on best practice recommendations from several countries, they are frequently not assessed. Barriers related to the nature of the screening tools (e.g., time consuming in high-volume clinics), practice environment (e.g., lack of human resources or space), as well as potential adopters (e.g., equipoise surrounding the benefits of treatment for these conditions) pose challenges to routine screening implementation. Simple, feasible approaches to routine screening coupled with appropriate, evidence-based treatment protocols are required to better identify and manage depression, obstructive sleep apnea, and cognitive impairment symptoms in stroke prevention clinic patients to reduce the impact of these important post-stroke comorbidities. These tools may in turn facilitate large-scale randomized controlled treatment trials of interventions for DOC conditions that may help to improve cardiovascular outcomes after stroke or TIA.

Adjusting for Drug Wastage in Economic Evaluations of New Therapies for Hematologic Malignancies: A Systematic Review.

PURPOSE: As costs of cancer care rise, there has been a shift to focus on value. Drug wastage affects costs to patients and health care systems without adding value. Historically, cost-effectiveness analyses have used models that assume no drug wastage; however, this may not reflect real-world practices. We sought to identify the frequency of drug wastage modeling in economic evaluations of modern parenteral therapies for hematologic malignancies. METHODS: We conducted a systematic literature review of economic evaluations of new US Food and Drug Administration-approved parenteral chemotherapies with indications for the treatment of hematologic malignancies. The primary outcome of interest was the proportion of studies that modeled drug wastage in base-case analyses. If wastage was considered in primary analyses, we reported the impact of wastage on incremental cost-effectiveness ratios (ICERs) and drug acquisition costs. RESULTS: Wastage was considered in base-case analyses in less than one third of all publications reviewed (12 of 38; 32%). Of these, two studies went on to complete sensitivity analyses and reported significant changes in the calculated ICER as a result. In one study, the ICER increased by 32%, and in the second, accounting for wastage changed a positive ICER to a dominant result. CONCLUSION: Potential costs associated with drug wastage are considered in only one third of modern cost-effectiveness models. The impact of wastage on calculated ICERs and drug acquisition costs is potentially substantial. The modeling of wastage in base-case and sensitivity analyses is recommended for future economic evaluations of new intravenous therapies for hematologic malignancies.

Blockade of CCR2 reduces macrophage influx and development of chronic renal damage in murine renovascular hypertension.

Renovascular hypertension (RVH) is a common cause of both cardiovascular and renal morbidity and mortality. In renal artery stenosis (RAS), atrophy in the stenotic kidney is associated with an influx of macrophages and other mononuclear cells. We tested the hypothesis that chemokine receptor 2 (CCR2) inhibition would reduce chronic renal injury by reducing macrophage influx in the stenotic kidney of mice with RAS. We employed a well-established murine model of RVH to define the relationship between macrophage infiltration and development of renal atrophy in the stenotic kidney. To determine the role of chemokine ligand 2 (CCL2)/CCR2 signaling in the development of renal atrophy, mice were treated with the CCR2 inhibitor RS-102895 at the time of RAS surgery and followed for 4 wk. Renal tubular epithelial cells expressed CCL2 by 3 days following surgery, a time at which no significant light microscopic alterations, including interstitial inflammation, were identified. Macrophage influx increased with time following surgery. At 4 wk, the development of severe renal atrophy was accompanied by an influx of inducible nitric oxide synthase (iNOS)+ and CD206+ macrophages that coexpressed F4/80, with a modest increase in macrophages coexpressing arginase 1 and F4/80. The CCR2 inhibitor RS-102895 attenuated renal atrophy and significantly reduced the number of dual-stained F4/80+ iNOS+ and F4/80+ CD206+ but not F4/80+ arginase 1+ macrophages. CCR2 inhibition reduces iNOS+ and CD206+ macrophage accumulation that coexpress F4/80 and renal atrophy in experimental renal artery stenosis. CCR2 blockade may provide a novel therapeutic approach to humans with RVH.

Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-ß-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

New Considerations in the Design of Clinical Trials for Bone Metastases.

Palliative radiotherapy (RT) is prescribed to patients with bone metastases to alleviate symptoms and improve quality of life. The lack of consistent endpoints for such trials has made cross study comparison difficult and has led to contradictory conclusions. The International Bone Metastases Consensus Working Party was established to create a standard set of endpoints and recommendations for future clinical trials. Recommendations were included regarding eligibility criteria, pain assessments, follow-up assessments, timing, as well as radiation techniques. Suggestions were also made to facilitate the ease with which different studies could be compared as well as to encourage widespread consistency in certain aspects of trial design. Investigators conducting clinical trials in bone metastases should continue to adopt these recommendations to ensure consistent guidelines based on the most recent literature.

The EORTC QLQ-BN20 for assessment of quality of life in patients receiving treatment or prophylaxis for brain metastases: a literature review.

INTRODUCTION: Brain metastases occur in approximately 20-40% of cancer patients during the course of disease. As treatment for brain metastases is palliative over curative, quality of life (QoL) is emphasized over prolonged survival. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20 is a QoL assessment specific to brain neoplasms. We aim to provide a review of the current use of the EORTC QLQ-BN20 for patients with brain metastases. MATERIALS & METHODS: All studies utilizing the QLQ-BN20 for QoL assessment in patients receiving treatments related to brain metastases were included. Study information including treatment type, assessment periods, patient enrolment and all information pertaining to the QLQ-BN20 were extracted. RESULTS: A total of 13 studies were identified, five of which were randomized trials assessing prophylactic whole brain radiation for patients with small-cell lung cancer. The QLQ-BN20 was used in conjunction with the core QLQ-C30 questionnaire in all but one of the studies and together these comprised the entire QoL assessments for 11 of the 13 studies. Neurocognitive function assessments supplemented QoL in four studies and accompanying performance status indices used with the QLQ-BN20 varied. Compliance issues were commonly cited. QoL changes during study periods varied as improvements, deteriorations and stabilizations were all observed. CONCLUSION: QoL assessments should be conducted using disease-specific tools. Future studies should minimize patient burden in order to maximize data collection and accrual. A common set of QoL end points for patients with brain metastases should be created.

FACT-Br for assessment of quality of life in patients receiving treatment for brain metastases: a literature review.

INTRODUCTION: Brain metastases are a significant cause of morbidity and mortality for patients with advanced cancers, and quality-of-life (QoL) end points are most appropriate for this population. The Functional Assessment of Cancer Therapy (FACT) questionnaires are commonly used to assess cancer-related QoL issues. The FACT-Brain (FACT-Br) provides an additional set of disease-specific questions pertaining to brain neoplasms. We aim to provide a comprehensive review to examine the use of the FACT-Br as a QoL assessment for patients with brain metastases. MATERIALS & METHODS: A review of the literature was conducted and all studies utilizing the FACT-Br for QoL assessment of patients with brain metastases were included. Study information and relevant information regarding the FACT-Br were extracted. RESULTS: A total of 14 studies were identified representing various treatment options (radiation, chemotherapy and surgery) for patients with brain metastases. All studies utilized at least part of the FACT-Br as the main QoL assessment. In addition, neurocognitive and performance status assessments were performed in nine and 12 out of 14 studies, respectively. Issues of poor accrual, compliance and attrition were common and posed problems in reaching statistically significant changes in QoL despite changes in raw QoL scores. CONCLUSION: Studies involving patients with brain metastases should continue to utilize QoL tools such as the FACT-Br; however, this tool still requires validation for use in this patient population. Additional studies should observe the relationship between neurocognitive function and QoL, and attempt to minimize poor accrual and compliance issues through modifications of trial design and reduction of patient burden.

Comparison of the EORTC QLQ-C15-PAL and the FACIT-Pal for assessment of quality of life in patients with advanced cancer.

Shorter quality-of-life (QoL) assessments are beneficial for palliative patients as they reduce burden associated with completing personal, and at times stressful, questionnaires. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL) and the Functional Assessment of Chronic Illness Therapy - Palliative Care (FACIT-Pal) are two palliative QoL tools that have been validated for use in this population. The purpose of this article was to conduct a review of studies utilizing these two palliative-specific QoL instruments, their development and their relative strengths for use in advanced cancer patients. Studies detailing the development process for the QLQ-C15-PAL and the FACIT-Pal were identified. A comparison between both questionnaires in terms of development, characteristics, validation and use was conducted. The QLQ-C15-PAL was developed via structured shortening of the longer core instrument, the Quality of Life Questionnaire Core 30 (QLQ-C30), whereas the FACIT-Pal includes the Functional Assessment of Cancer Therapy - General tool plus a new 19-item palliative scale created through interviews with patients and healthcare professionals. Although significant overlap exists between both tools, there is a marked difference in the aspects of QoL assessed. Scoring, organization and item format are different; however, response options and recall period are the same. Both tools cover the core items relevant to patients with advanced cancers and can be supplemented with disease-specific tools. Both QLQ-C15-PAL and FACIT-Pal allow for assessment of QoL issues specific to patients with advanced diseases. Each instrument has unique strengths and weaknesses and choice between these tools is dependent on the investigator and study needs. Future studies should directly compare these two tools and validate their use through a number of administration modes.

In utero cell transfer between porcine littermates.

Trafficking of cells between mother and fetus during the course of normal pregnancy is well documented. Similarly, cells are known to travel between twins that share either a placenta (i.e. monozygotic) or associated chorion (i.e. monochorionic). Transferred cells are thought to be channelled via the vessels of the placenta or vascular connections established via the chorion and the long-term presence of these cells (i.e. microchimerism) can have important consequences for immune system function and reparative capacity of the host. Whether cells can be transferred between twins with separate placentas and separate chorions (i.e. no vascular connections between placentas) has not been investigated nor have the biological consequences of such a transfer. In the present study, we tested the possibility of this type of cell transfer by injecting human cord blood-derived cells into a portion of the littermates of swine and probing for human cells in the blood and tissues of unmanipulated littermates. Human cells were detected in the blood of 78% of unmanipulated littermates. Human cells were also detected in various tissues of the unmanipulated littermates, including kidney (56%), spleen (33%), thymus (11%) and heart (22%). Human cells were maintained in the blood until the piglets were sacrificed (8 months after birth), suggesting the establishment of long-term microchimerism. Our findings show that the transfer of cells between fetuses with separate placentas and separate chorions is significant and thus such twins may be subject to the same consequences of microchimerism as monozygotic or monochorionic counterparts.

Poor Accrual in Palliative Research Studies: An Update From the Rapid Response Radiotherapy Program.

BACKGROUND: In June 2003, the Rapid Response Radiotherapy Program (RRRP) implemented changes to recruitment strategies in attempts to increase patient accrual to research studies. Such modifications included the use of a dedicated research assistant to screen for and identify eligible study patients, the introduction of more appropriate inclusion criteria, and the switch towards telephone interviews to minimize patient burden. The purpose of this study is to provide an update on patient accrual in the RRRP. METHODS: All patients seen in the RRRP from January 2002 to December 2009 were recorded in a prospective database. Reasons for referral, eligibility for clinical trials, reasons for non-accrual, and various demographics information were recorded. Descriptive statistics summarized findings. RESULTS: A total of 4726 patient visits were recorded from January 1st, 2002 to December 31st, 2009. Prior to changes, the overall rate of accrual into research studies was 14.9% versus 48.1% after changes were implemented. Patients were not accrued onto studies mainly to due ineligibility according to study protocol. Other reasons such as language barrier (12.1%), physician objection (3.5%), patient declining participation (11.3%) and lack of a research assistant (9.3%) were cited. CONCLUSIONS: Changes in clinical structure and study design can significantly impact accrual patterns in palliative radiotherapy studies. Despite these changes however, the majority of patients are still not enrolled in studies. Therefore additional efforts need to be made to maximize patient accrual and minimize attrition.