Defining repetitive behaviours in frontotemporal dementia.

Repetitive behaviours are common manifestations of frontotemporal dementia (FTD). Patients with FTD exhibit various types of repetitive behaviours with unique behavioural and cognitive substrates, including compulsivity, lack of impulse control, stereotypy and hoarding. Other sources of repetitive behaviours, such as restrictive interests and insistence on sameness, may also be seen in FTD. Although repetitive behaviours are highly prevalent and potentially discriminatory in this population, their expression varies widely between patients, and the field lacks consensus about the classification of these behaviours. Terms used to describe repetitive behaviours in FTD are highly heterogeneous and may lack precise definitions. This lack of harmonization of the definitions for distinct forms of repetitive behaviour limits the ability to differentiate between pathological behaviours and impedes understanding of their underlying mechanisms. This review examines established definitions of well-characterized repetitive behaviours in other neuropsychiatric disorders and proposes operational definitions applicable to patients with FTD. Building on extant models of repetitive behaviours in non-human and lesion work and models of social behavioural changes in FTD, we describe the potential neurocognitive bases for the emergence of different types of repetitive behaviours in FTD and their potential perpetuation by a predisposition towards habit formation. Finally, examples of distinct therapeutic approaches for different forms of repetitive behaviours are highlighted, along with future directions to accurately classify, measure and treat these symptoms when they impair quality of life.

Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers.

While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.

Studying sense of agency online: Can intentional binding be observed in uncontrolled online settings?

Intentional binding is often used as an implicit index of the sense of agency. However, intentional binding research has primarily been conducted in controlled lab environments. During the COVID-19 global pandemic, there has been a shift to implementing studies using online platforms and it is an open question whether the intentional binding effect can be found using an online experimental set-up and participant sample. Here, we address this question by asking online participants to complete the Libet clock version of the intentional binding task, which we make freely available to researchers as a jsPsych (De Leeuw, 2014) plugin. Intentional binding was observed in the form of later keypress estimates and earlier auditory tone estimates, when the auditory tone followed the keypress. These findings confirm that intentional binding can be assessed in online contexts. We discuss these findings in relation to the broader intentional binding literature.

Surgical tracheostomy in children with malignancy receiving intensive chemotherapy: A case series and review of literature.

We retrospectively reviewed a paediatric intensive care unit database that supports a tertiary oncology service to explore safety and outcome of tracheostomy in oncology patients over a 12-year period and reviewed literature. A total of 895 patients were admitted with a haematological or a solid tumour malignancy of which 222 were ventilated. Six of 222 (2.7%) ventilated children were tracheostomised. Four of six children tracheostomised for ventilatory support received intensive chemotherapy complicated by neutropenia and thrombocytopenia. There was no significant tracheostomy-related complication. Tracheostomy improved patient comfort, reduced sedative requirement, and may have helped recovery. Tracheostomy should be considered early in selected children with haemato-oncological diagnoses requiring prolonged ventilation.

Social exclusion reduces the sense of agency: Evidence from intentional binding.

Social exclusion is known to induce an immediate threat to one's perceived sense of control. The sense of agency is an important human experience, strongly associated with volitional action. Healthy participants perceive the temporal interval between a voluntary action and its effect to be shorter than the same interval when it separates an involuntary action and effect. This temporal illusion is known as intentional binding and is used experimentally to index the implicit sense of agency. The current study investigated whether activating memories of social exclusion alters intentional binding. Results show that action-effect interval estimates are significantly longer after remembering an episode of social exclusion than after remembering an episode of social inclusion, or a no priming baseline condition. This study is the first to demonstrate the link between feelings of social exclusion and the pre-reflective sense of agency.

Systematic review and meta-analysis of appendiceal carcinoid tumors in children.

OBJECTIVE: The study's aim was to review the literature regarding past and current practices in managing incidental appendiceal carcinoid tumors and need for more procedures. METHOD: A search of MEDLINE, Embase, CINAHL, and Cochrane databases of systematic reviews was undertaken of the English language literature. The mesh terms used were "carcinoid" or "neuroendocrine," "tumour" or "tumor," "appendix," "appendicectomy," or "appendectomy," and "child," "pediatric," or "paediatric." Of the 369 articles found, 37 met the inclusion criteria. Our hospital records and pathology database identified 11 patients with confirmed histological diagnosis of appendicular carcinoids from January 1996 to December 2016. Those cases were also included in this study. RESULTS: A total of 958 cases were identified from the literature and our own experience. There were 566 females and 343 males giving us a ratio of 1.65:1. The frequency was 0.3% of appendicectomies. There was a 28-fold increase in the risk of having a positive lymph node if the tumor size was >2 cm compared with the risk of having a positive lymph node if the tumor size was ≤2 cm. There was no recurrence or mortality for those with criteria for secondary surgery, who were observed after appendicectomy compared to those that had secondary surgery. Mean follow-up was 58.6 months (4.8 years) with a range of 0-396 months (33 years). CONCLUSION: Appendicectomy alone is an adequate treatment for an appendicular carcinoid in children irrespective of size, position, lymph node, or mesenteric involvement. Post-appendicectomy investigations were found to be not helpful in this study.

Non-literacy biased, culturally fair cognitive detection tool in primary care patients with cognitive concerns: a randomized controlled trial.

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32-5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644 .

The sense of agency for brain disorders: A comprehensive review and proposed framework.

Sense of Agency (SoA) refers to the feeling of control over voluntary actions and the outcomes of those actions. Several brain disorders are characterized by an abnormal SoA. To date, there is no robust treatment for aberrant agency across disorders; this is, in large part, due to gaps in our understanding of the cognitive mechanisms and neural correlates of the SoA. This apparent gap stems from a lack of synthesis in established findings. As such, the current review reconciles previously established findings into a novel neurocognitive framework for future investigations of the SoA in brain disorders, which we term the Agency in Brain Disorders Framework (ABDF). In doing so, we highlight key top-down and bottom-up cues that contribute to agency prospectively (i.e., prior to action execution) and retrospectively (i.e., after action execution). We then examine brain disorders, including schizophrenia, autism spectrum disorders (ASD), obsessive-compulsive disorders (OCD), and cortico-basal syndrome (CBS), within the ABDF, to demonstrate its potential utility in investigating neurocognitive mechanisms underlying phenotypically variable presentations of the SoA in brain disorders.

The 5-Cog paradigm to improve detection of cognitive impairment and dementia: clinical trial protocol.

Cognitive impairment related to dementia is under-diagnosed in primary care despite availability of numerous cognitive assessment tools; under-diagnosis is more prevalent for members of racial and ethnic minority groups. Clinical decision-support systems may improve rates of primary care providers responding to positive cognitive assessments with appropriate follow-up. The 5-Cog study is a randomized controlled trial in 1200 predominantly Black and Hispanic older adults from an urban underserved community who are presenting to primary care with cognitive concerns. The study will validate a novel 5-minute cognitive assessment coupled with an electronic medical record-embedded decision tree to overcome the barriers of current cognitive assessment paradigms in primary care and facilitate improved dementia care.

Dementia is common, though under-recognized, in older adults (OAs). Primary care providers (PCPs) miss opportunities to help patients and their families manage the disease because of failure to, or delay to, make an appropriate diagnosis. Black and Hispanic OAs are more likely than White OAs to experience delayed diagnosis. Most available memory tests are too long for practical use by PCPs, and are ill suited to patients of diverse language, cultural and educational backgrounds. Studies have shown that even when patients test positive for dementia in primary care, PCPs often do not take follow-up action. Our improved memory test, the 5-Cog, is brief (5 min), not biased by language issues (uses pictures and symbols instead of words), and simple (doesn't require expensive technology and complex staff training). The 5-Cog is paired with a clinical decision support tool, providing tailored recommendations directly into the patient's medical record, and making it easier for PCPs to take appropriate action. This study will evaluate whether the 5-Cog paradigm results in improved dementia care.

Telehealth for the cognitively impaired older adult and their caregivers: lessons from a coordinated approach.

The Covid-19 pandemic forced providers to alter their delivery of care to special populations, including older adults with cognitive impairment. The Montefiore-Einstein Center for the Aging Brain, a specialty multidisciplinary center for the evaluation and management of patients with neurodegenerative disorders, developed a coordinated approach (Coordinated Care At Risk/Remote Elderly program [CCARRE]) to reach our diverse population during the initial Covid-19 crisis in New York City, USA. In the tele-evaluation of the first 85 patients seen with CCARRE, we recognized unique factors that could improve patient care, lessen burden and optimize access to community resources. Lessons learned from the experience are shared.

Anterior mediastinal masses - A multidisciplinary pathway for safe diagnostic procedures.

OBJECTIVE: The objective of this study was to report our multidisciplinary diagnostic approach for patients with anterior mediastinal masses (AMM). METHODS: A retrospective review of patients with AMM at a tertiary pediatric surgical oncology centre (January 2011-December 2016) was performed. We analyzed data on clinical presentation, mode of tissue diagnosis, anesthetic techniques, and complications. RESULTS: Of the 44 patients admitted with AMM (median age 11 years, 27 males and 17 females), 22 had respiratory symptoms. Imaging revealed tracheobronchial compression in 26 children. Twenty patients had a lymph node biopsy. Ten patients had image-guided core biopsy of the mediastinal mass, and 2 had mediastinoscopic biopsy of a paratracheal lymph node. One patient with likely recurrence of a relapsed metastatic ethmoid carcinoma did not have a biopsy. The diagnosis was made from alternative tissues, such as pleural fluid in 4 and peripheral blood in 7 patients. Twenty-five anesthetics were assessed, as 14 patients required no or only local anesthesia, and 5 had unavailable anesthetic notes. Eighteen of 25 patients were anesthetized maintaining spontaneous breathing, mostly by means of ketamine sedation. There were no major anesthetic complications. CONCLUSION: Safe tissue diagnosis of anterior mediastinal masses can be obtained by a personalized multidisciplinary approach. Use of alternative tissues, local anesthesia, and ketamine sedation help minimize the need for general anesthesia, muscle paralysis, and controlled ventilation. LEVEL OF EVIDENCE: IV (Case Series with no Comparison Group).

High-dose etoposide and cyclophosphamide in adults and children with primary refractory and multiply relapsed acute leukaemias: The Royal Marsden experience.

INTRODUCTION: For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital. PATIENTS AND METHODS: Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015. RESULTS: Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%). CONCLUSIONS: HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials.

Picture-Based Memory Impairment Screen: Effective Cognitive Screen in Ethnically Diverse Populations.

OBJECTIVES: To describe the psychometric properties of the Picture-based Memory Impairment Screen (PMIS) in a multidisciplinary memory disorder center serving an ethnically and educationally diverse community. DESIGN: Cross-sectional cohort study. SETTING: Montefiore Center for Aging Brain (CAB) PARTICIPANTS: Individuals with cognitive complaints (N=405; average age 76±10, 66% female). MEASUREMENTS: A geriatrician or neurologist administered the PMIS, and a neuropsychologist administered the Blessed Information, Memory, and Concentration (BIMC) test and determined whether participants had dementia, mild cognitive impairment (MCI), or subjective cognitive complaints (SCC). RESULTS: Mean PMIS scores were 4.0±2.6 in participants with dementia (n=194), 6.8±1.5 in those with MCI (n= 155), and 7.0±1.8 in those with SCC (n= 56) (p<.001). PMIS scores showed similar significant linear trends when analyzed according to ethnicity, education, sex, and language. The PMIS was negatively correlated with BIMC score (p<.001). The PMIS had positive predictive value of 77%, negative predictive value of 73%, sensitivity of 68%, and specificity of 81% to detect all-cause dementia in this population of individuals with cognitive complaints. CONCLUSION: The PMIS is a quick, valid screening tool to identify cognitive impairment in individuals with cognitive complaints that accounts for cultural and educational differences.

Montefiore-Einstein Center for the Aging Brain: Preliminary Data.

Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one-year experience with outpatient based dementia care at the Montefiore-Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non-pharmacological treatments as appropriate, and the facilitation of access to clinical trials. The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self-identified ethnicity of patients included Caucasian (26%), African-American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one-year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians.

Older adults with heel ulcers in the acute care setting: frequency of noninvasive vascular assessment, surgical intervention, and 1-year mortality.

OBJECTIVES: To examine how often hospitalized older adults with a diagnosis of heel ulcers are evaluated with noninvasive vascular tests and to determine the impact of invasive vascular or surgical procedures on 1-year mortality. DESIGN: Retrospective review using an electronic database and chart review of all patients discharged with a diagnosis of heel ulcer between 2006 and 2009. SETTING: Urban teaching hospital. PARTICIPANTS: A total of 506 participants aged 65 years and older. MEASUREMENTS: Data collected included resident characteristics (demographics, medical history, and severity of illness using the Charlson comorbidity index), staging of heel ulcers, rates of noninvasive vascular assessments, vascular and surgical procedures, length of stay, and 1-year mortality. RESULTS: Thirty-one percent (155/506) of patients with a heel ulcer underwent noninvasive vascular testing and of these 83% (129/155) were found to have underlying ischemia. Twenty-six percent (130/506) of patients underwent at least 1 vascular or surgical procedure. The 1-year mortality rate for patients with stage 1 or 2 disease was 55%; this rose to 70% for patients with stage 3 or 4 ulcers (P = .01), and could not be explained by differences in the Charlson comorbidity index. Patients who underwent a vascular or surgical procedure had a significantly lower mortality compared with those who did not (59% vs 68% P = .04). CONCLUSION: Older adults with a heel ulcer in the acute care setting are frequently not assessed for underlying ischemia of the lower extremities. The diagnosis carries high 1-year mortality rates. Evidence-based protocols need to be developed to determine which older adults should have a vascular assessment and then undergo an invasive procedure.

Clinical characteristics and outcome of pediatric patients with stage IV Hodgkin lymphoma.

BACKGROUND AND OBJECTIVES: While treatment outcomes for patients with Hodgkin lymphoma (HL) have improved remarkably, patients with disseminated disease still have a poorer outcome. Stage IV HL is often reported with other 'advanced stage' categories, confusing the specific contribution of disease dissemination to the outcome. This single-institution report looks at characteristics and outcomes of this specific category. PATIENTS AND METHODS: The medical records of pediatric HL patients (< 14 years) from 1975 through 2003 were retrospectively reviewed and the data analyzed. RESULTS: Stage IV patients (n = 67) had more poor-risk characteristics than patients in stages I-III (n = 300) (B symptoms 86.6% vs. 19.3%, bulky disease 57.6% vs. 45.5% and mediastinal mass 77.6% vs. 29.7%; P < .001 for all characteristics). The liver was the most common extralymphatic site (in 51.5% of patients with stage IV disease. Stage IV patients received chemotherapy (CT) alone (n = 55) or combined modality therapy (CMT) (n = 12). Fifty-four patients (80.6%) achieved complete remission, 2 (3%) partial remission, 10 (14.9%) had progressive disease and 1 was lost to follow up. Overall survival was 79.4% and event-free survival (EFS) was 63.9% at 5 years. There was a non-significant benefit for CMT (OS = 91.7% v. 77.1%, P = .3; EFS = 70.7% v. 62.7%, P = .3). Ten of 12 relapsed and only 1 of 10 progressive disease patients were salvaged. On multivariate analysis, failure to achieve complete remission with CT was associated with a poorer outcome. CONCLUSION: Stage IV disease is associated with poor risk features and confers a worse outcome than stage I-III disease. Achievement of complete remission with CT is an important prognostic feature. Slow responders may require novel and/or aggressive therapy to achieve complete remission.

Association between alcohol consumption and both osteoporotic fracture and bone density.

OBJECTIVE: Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling. METHODS: MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force. RESULTS: We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk=0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk=1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers. CONCLUSION: Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.

Hodgkin lymphoma in very young children: Clinical characteristics and outcome of treatment.

In developed nations, Hodgkin lymphoma (HL) is rare in <5-year olds and represent a minority in developing countries. Little is reported about the biology and behavior of these very young patients compared with older children. 18.75% of our pediatric HL patients (0 - 14 years) were <5 years at diagnosis. This group had more boys, similar incidence of B-symptoms and stage distribution, less mediastinal involvement and bulky disease, and more mixed cellularity subtype than older children. Treatment included chemotherapy (CT; n = 55), combined modality therapy (CMT; n = 12) and XRT only (n = 2). Ten-year EFS and OS was 81.5% and 90.4%, respectively, versus 75.5% and 90.5% for older children (p > 0.5). A trend toward better survival was seen with CMT, using very LD-XRT, than with CT (OS 100% vs. 86.4%[p = 0.3]; EFS 90.9% vs. 81.0%[p = 0.4]). Although CT could be effective in a subset of LR patients, LD-XRT may be needed to effectively treat most of these patients. This dose reduction may reduce XRT-related toxicity, which can be significant in very young children.

Vitamin D and secondary hyperparathyroidism in the institutionalized elderly: a literature review.

Low vitamin D status is recognized as a prevalent disorder in certain high-risk groups. The greatest prevalence has been reported in the institutionalized elderly. The goal of this article is to review the literature pertaining to vitamin D deficiency in the institutionalized elderly and to highlight the need for treatment in this high-risk group. A computer search for English language articles from 1980 to February 2007 was conducted using the PubMed database and key words vitamin D, hyperparathyroidism, elderly, institutionalization, and nursing home. Several risk factors have been noted, which are more prominent in the institutionalized elderly, including decreased sun exposure, poor oral intake, and multiple comorbidities. Long-term care residents should be prescribed higher doses of calcium and vitamin D for adequate bone mineral density and fracture prevention.