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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.

BackgroundThe DOC screen was developed to identify Depression, Obstructive sleep apnea, and Cognitive impairment (“DOC” comorbidities) after stroke. Each component has its own score, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure. We assessed the added value of using DOC screen completion time as a predictor of impairment on detailed cognitive assessments.MethodsConsecutive English-speaking new referrals to the stroke prevention clinic were consented to participate in detailed neuropsychological testing (n=437). DOC screen scores and times were compared to cognitive test scores using multiple linear regression and receiver operating characteristic (ROC) analysis. All linear regression analyses controlled for age, sex, years of education, and functional outcome as assessed by the modified Rankin score.ResultsAverage completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for age, sex and cognitive screen score, completion time was a significant independent predictor, of speed of processing (p = .002, 95% CI: -0.016 to -0.004), verbal fluency (p < .001, CI: -0.012 to -0.006) and executive (p = .004, CI: -0.006 to -0.001), but not memory, function. Completion time above 5.5 minutes (332.5 seconds) was associated with a high likelihood of impairment on gold standard executive (likelihood ratios 3.9-5.2) and speed of processing (likelihood ratio = 5.2) tasks.ConclusionsDOC screen completion time is easy to collect in routine care and is independently associated with speed of processing, language and executive dysfunctions after stroke. People who take more than 5.5 minutes to complete the DOC screen are likely to have deficits in executive functioning and speed of processing. These domains can be challenging to screen for in stroke survivors, and this measure provides a simple, clinically feasible method to screen for these under-appreciated concerns.Clinical Trials Registration Identifier:NCT02363114Clinical Trials URL:https://clinicaltrials.gov/ct2/show/NCT02363114

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.

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.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.Using hierarchical linear regressions, apathy scores significantly predicted semantic fluency performance (β = -.159, p = .020), but not phonemic fluency performance (β = -.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 (β = -.035, p = .554) or phonemic fluency (β = -.081, p = .173). Apathy and depressive symptoms were moderately correlated, r(280) = .58, p .001.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.

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.

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.

We report the ccase of a 65-year-old woman presenting with urosepsis in the context of a one-week history of progressive right flank pain and a past medical history of type 2 diabetes mellitus. Computed Tomography (CT) demonstrated evidence of emphysematous pyelitis, a rare infection caused by gas-producing bacteria associated with elevated blood glucose. The patient responded well to fluid resuscitation and was discharged home with follow-up arranged for blood sugar management and outpatient lithotripsy addressing obstructive renal calculus.

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.

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).

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.

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. doi:10.4021/wjon357w

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.

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.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.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.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.

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.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.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.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.

Well-being falls within a broad category of quality of life indicators and encompasses both physical and emotional factors. Identification of the most important factors affecting overall well-being may allow health care practitioners to target these symptoms and improve patients' quality of life. The purpose of this study was to determine factors most predictive of well-being in advanced cancer patients.Patients referred to the Rapid Response Radiotherapy Program completed the Edmonton Symptom Assessment System (ESAS) at consultation. ESAS scores and demographics were analysed for their predictive ability for well-being via regression analysis of the raw and categorical scores.In total, 1439 ESAS assessments were analysed; the median age was 69 years (range 21-95). The most common primary cancers were of the lung (36%), breast (21%) and prostate (18%). Greater distress in all ESAS items, lower Karnofsky performance status (KPS) and referral for bone metastases significantly predicted for worse well-being (all P0.0001). However, referral for brain metastases predicted for better well-being. In multivariate analysis, the most predictive factors for worse well-being were lower KPS (P = 0.003) and greater distress in drowsiness (P = 0.01), pain (P0.0001), fatigue (P0.0001), depression (P0.0001) and appetite loss (P0.0001). Repeated analyses with categorical scores led to similar results.Greater distress in physical and emotional symptoms assessed by ESAS contributes significantly to poorer well-being. Management for patients with advanced cancer should be directed towards these symptoms, as they form the basis for well-being. Although emotional symptoms may be scored lower than physical symptoms by patients, both significantly affect well-being.

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.