Smoking histories: a bioarchaeological approach to tobacco consumption in two skeletal populations from The Netherlands (1300-1829 CE).

Over the past decade, the history of tobacco's introduction to Europe and its societal impact has been extensively studied, resulting in prevailing narratives about its adoption and consumption. In the Netherlands, historical records generally concur that: (I) tobacco rose in popularity among all socioeconomic classes between 1590 and 1630 CE; and (II) it spread throughout the Country as a male habit. However, the presence and consumption of tobacco have exhibited profound variations across diverse societies throughout history, manifesting dissimilar patterns of employment and significance over varying temporal and spatial dimensions. By analysing a sample of 351 human skeletons dating from 1300 to 1829 CE, the present study challenges the limited historical narratives presented above and emphasizes the diverse contextual factors that influenced tobacco's prevalence in two different Dutch centres. Our results suggest that in certain areas of the Netherlands tobacco was likely present and widely consumed well before 1630 CE, while also highlighting overall substantial female participation in the practice. Furthermore, our analysis hints at the possibility of divergent methods of tobacco consumption between sexes, suggesting that the historical narrative of tobacco as solely a male habit may warrant reconsideration. Overall, our study contributes to a deeper understanding of the complex history of tobacco in the Netherlands, shedding light on historical trends and cultural practices.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Richter's transformation: Transforming the clinical landscape.

Richter transformation (RT) represents an aggressive histological transformation from chronic lymphocytic leukaemia, most often to a large B cell lymphoma. It is characterised by chemo-resistance and subsequent short survival. Drug development has struggled over recent years in light of the aggressive kinetics of the disease, lack of pivotal registrational trials and relative rarity of the phenomenon. In this review we will highlight the diagnostic and therapeutic challenges of managing patients with RT as well as taking a look to the future therapeutic landscape. Highly active therapies developed across B cell malignancies are starting to impact this field, with T-cell activation therapies (CAR-T, bispecific antibodies), antibody-drug conjugates, and novel small molecule inhibitor combinations (e.g. BTKi-BCL2i) being actively studied. We will highlight the data supporting these developments and look to the studies to come to provide hope for patients suffering from this devastating disease.

Recent advances in treatment of spatial neglect: networks and neuropsychology.

INTRODUCTION: Spatial neglect remains an underdiagnosed and undertreated consequence of stroke that imposes significant disability. A growing appreciation of brain networks involved in spatial cognition is helping us to develop a mechanistic understanding of different therapies under development. AREAS COVERED: This review focuses on neuromodulation of brain networks for the treatment of spatial neglect after stroke, using evidence-based approaches including 1) Cognitive strategies that are more likely to impact frontal lobe executive function networks; 2) Visuomotor adaptation, which may depend on the integrity of parietal and parieto- and subcortical-frontal connections and the presence of a particular subtype of neglect labeled Aiming neglect; 3) Non-invasive brain stimulation that may modulate relative levels of activity of the two hemispheres and depend on corpus callosum connectivity; and 4) Pharmacological modulation that may exert its effect primarily via right-lateralized networks more closely involved in arousal. EXPERT OPINION: Despite promising results from individual studies, significant methodological heterogeneity between trials weakened conclusions drawn from meta-analyses. Improved classification of spatial neglect subtypes will benefit research and clinical care. Understanding the brain network mechanisms of different treatments and different types of spatial neglect will make possible a precision medicine treatment approach.

Telemedicine impact on post-stroke outpatient follow-up in an academic healthcare network during the COVID-19 pandemic.

BACKGROUND: The expansion of telemedicine associated with the COVID-19 pandemic has influenced outpatient medical care. The objective of our study was to determine the impact of telemedicine on post-acute stroke clinic follow-up. METHODS: We retrospectively evaluated the impact of telemedicine in Emory Healthcare, an academic healthcare system of comprehensive and primary stroke centers in Atlanta, Georgia, on post-hospital stroke clinic follow-up. We compared the frequency of 90-day follow-up in a centralized subspecialty stroke clinic among patients hospitalized before the local COVID-19 pandemic (January 1, 2019- February 28, 2020), during (March 1- April 30, 2020) and after telemedicine implementation (May 1- December 31, 2020). A comparison was made across hospitals less than 1 mile, 10 miles, and 25 miles from the stroke clinic. RESULTS: Of 1096 ischemic stroke patients discharged home or to a rehab facility during the study period, 342 (31%) had follow-up in the Emory Stroke Clinic (comprehensive stroke center 46%, primary stroke center 10 miles away 18%, primary stroke center 25 miles away 14%). Overall, 90-day follow-up increased from 19% to 41% after telemedicine implementation (p<0.001) with telemedicine appointments amounting for up to 28% of all follow-up visits. In multivariable analysis, factors associated with teleneurology follow-up (vs no follow-up) included discharge from the comprehensive stroke center, thrombectomy treatment, private insurance, private transport to the hospital, NIHSS 0-5 and history of dyslipidemia. CONCLUSIONS: Despite telemedicine implementation at an academic healthcare network successfully increasing post-stroke discharge follow-up in a centralized subspecialty stroke clinic, the majority of patients did not complete 90-day follow-up during the COVID-19 pandemic.

Impacts of Prism Adaptation Treatment on Spatial Neglect and Rehabilitation Outcome: Dosage Matters.

We examined whether number of prism adaptation treatment (PAT) sessions in regular clinical practice would predict spatial neglect (SN) improvement and rehabilitation outcomes. We reviewed clinical records from 16 U.S. rehabilitation hospitals where neurological patients were assessed for SN using the Catherine Bergego Scale (CBS) and if SN was detected, and may have received PAT. Multiple linear regression was used to predict CBS Change (indicating SN improvement) in 520 patients who received PAT while considering age, sex, diagnosis, time post diagnosis, CBS at baseline, neglected side of space, and length of stay. Another set of regression models including the same variables and adding Function Independent Measure (FIM®) at admission was used to predict FIM Gains (indicating rehabilitation outcomes) in 1720 patients receiving PAT or not. We found that greater number of PAT sessions predicted greater CBS Change, especially in patients with moderate-to-severe neglect. Number of PAT sessions also positively correlated with Total FIM, Motor FIM, and Cognitive FIM Gains regardless of SN severity classification at baseline. Furthermore, number of PAT sessions predicted CBS Change and FIM Gains among patients completing ≤8 PAT sessions but not among patients with ≥8 sessions, who however, showed greater CBS Change with increased PAT frequency (i.e., fewer days between two consecutive sessions). Receiving more once-daily PAT sessions predicted greater improvement in SN and rehabilitation outcomes. Receiving PAT at a higher frequency for 8 or more sessions predicted better SN improvement. Thus, dosage matters. The study provides practice-based evidence that PAT is appropriate for inpatient rehabilitation.

Efficacy of contralaterally controlled functional electrical stimulation compared to cyclic neuromuscular electrical stimulation and task-oriented training for recovery of hand function after stroke: study protocol for a multi-site randomized controlled trial.

BACKGROUND: Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites. METHODS: Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment. DISCUSSION: Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018.

Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study.

BACKGROUND: Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. METHODS: This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. RESULTS: A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin's tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours. CONCLUSIONS: This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

Prism Adaptation Treatment of Spatial Neglect: Feasibility During Inpatient Rehabilitation and Identification of Patients Most Likely to Benefit.

Objective: Spatial Neglect is prevalent among stroke survivors, yet few treatments have evidence supporting efficacy. This study examines the feasibility of Prism Adaptation Treatment (PAT) within an inpatient rehabilitation facility and the degree by which PAT improves symptoms of spatial neglect and functional independence among sub-acute survivors of right hemispheric stroke. Design: In this retrospective cohort study, 37 right hemispheric stroke patients were identified as having received at least 4 PAT sessions during their inpatient stay. Spatial neglect and functional independence levels of patients in the PAT cohort were compared to a matched active control group comprised of rehabilitation patients receiving alternative therapies to address neglect admitted during the same time period. Results: Most patients received the full recommended 10 sessions of PAT (average sessions completed = 8.6). A higher percentage of severe neglect patients receiving PAT (69%) displayed clinically significant gains on FIM (≥22 points) compared to those receiving alternative treatments (6%). Patients with mild or moderate neglect in the PAT cohort did not exhibit greater benefit than controls. Conclusion: Provision of PAT for treatment of spatial neglect in right hemispheric stroke patients was feasible during the inpatient rehabilitation admission. Patients with severe neglect showed the most benefit from PAT. Clinical Trial Registration: This study was registered as a retrospective observational study on Itab Clinical Trials.gov. NCT04977219.

Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT.

Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of <20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 × 107/m2. Twenty-three BMT recipients with relapsed/refractory (n = 11) and/or high-risk (n = 12) acute myeloid leukemia (n = 20) and acute lymphoblastic leukemia (n = 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n = 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post-TAA-T. The poorest prognosis patients (relapsed <6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n = 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n = 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-ß sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.

Effect of Missed Items on the Reliability of the Kessler Foundation Neglect Assessment Process.

OBJECTIVE: To determine the maximum permissible number of missed items on the 10-item Catherine Bergego Scale administered after the Kessler Foundation Neglect Assessment Process (KF-NAP). Secondary objectives were to determine the frequency, characteristics, and most commonly cited reasons reported for missed items. DESIGN: Retrospective diagnostic accuracy study. SETTING: Sixteen inpatient rehabilitation facilities in the United States. PARTICIPANTS: A consecutive clinical sample of 4256 patients (N=4256) with stroke or other neurologic deficits who were assessed for spatial neglect with the KF-NAP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Catherine Bergego Scale via KF-NAP. RESULTS: The majority (69.7%) of patients had at least 1 missed item on their KF-NAP. Among those with missed items, it was most common to have 2 missed items (51.4%), and few had more than 3 missed items (11.3%). The most commonly missed items were Collisions (37.2%), Cleaning After Meals (36.1%), Meals (34.0%), and Navigation (19.7%). The most commonly reported reasons for missed items included time constraints, cognitive or communication deficits, and behavior or refusal of the therapy session. These reasons were reported for nearly all item types. Item-specific reasons were also commonly reported, such as a lack of a needed resource for task completion or low functional status of the patient. Prorated scoring of measures with up to 3 missed items maintained an acceptable level of concordance with complete measures (Lin's Concordance Correlation Coefficient=0.96, 95% CI, 0.9478-0.9626) for the combination of 3 missed items with lowest concordance. CONCLUSIONS: Clinicians should make every effort to capture all items on the KF-NAP. However, missed items occur in the majority of cases because of patient factors and barriers inherent to the inpatient hospital setting. When missed items are necessary, clinicians can confidently interpret a prorated score when 7 or more items are scored.

The Implementation Process of Two Evidence-Based Protocols: A Spatial Neglect Network Initiative.

Introduction: Spatial neglect, a neurocognitive disorder of lateralized spatial attention, is prevalent among stroke survivors especially in inpatient rehabilitation facilities (IRFs). The ultimate goal of the project was to improve spatial neglect care in inpatient rehabilitation and trained as many OTs as possible using both tools in their regular practices as the means to achieve our overall objective. Therefore, we conducted a project aimed at implementing two evidence-based protocols, one for assessment (KF-NAP®) and the other for treatment (KF-PAT®), and share the implementation process, which included barriers and facilitators identified during and after the process, and implementation outcomes. Methods: Sixteen IRFs were involved. The Knowledge-To-Action Cycle was used to describe the process of knowledge inquiry (training), translating knowledge (implementation) and evaluating the use of knowledge in clinical practice (outcomes). Barriers and strategies were reported using the Consolidated Framework for Implementation Research and identified through a survey, after the study concluded. Results: Thirty-two therapists at the participating sites were trained to some level of the KF-NAP and KF-PAT. Throughout the project and also once after it finished, different barriers were identified by researchers and clinicians, who then determined together actions to eliminate or minimize the barriers. For example, multiple sites reported: "not having time to train other staff at their hospital due to high patient volume and other responsibilities." Discussion: The project shared our implementation process which demonstrated the importance of using implementation methods and incorporating a researcher-clinician partnership, not only for knowledge generation but also knowledge translation. Frequent communications and exchanging information with stakeholders at different levels, may be determinant to the success of each implementation phase. Further research is needed.

Human papillomavirus and head and neck squamous cell carcinoma in a UK population: Is there an association?

Background: Human papillomavirus (HPV) is an evolving important risk factor for head and neck cancer (HNC), especially for individuals who do not smoke and drink alcohol. The aim of this study was to establish the prevalence of HPV infection and elucidate its association with head and neck squamous cell carcinoma (HNSCC) patients in UK population. Methods: The presence and association of HPV was investigated in HNSCC patients in this retrospective clinical study. Samples were obtained from archived biopsies and resections. HPV screening was performed by the use of polymerase chain reaction (PCR) using the GP5+/GP6+ and the SPF1/2 consensus as primers and by immunohistochemistry (IHC). Samples of viral warts that were IHC positive for HPV and fibroepethelial polyps (FEP) were used, as positive and negative controls, respectively. Results: The cohort included 124 patients with HNSCC with an age range of 27-97 years (median, 60 years) and a male to female ratio of 2:1. Among the 124 HNSCC, 43/124 (34.7%) were from the tongue, 74/124 (60%) presented with advanced stage III or IV disease, 112/124 (90%) had a conventional phenotype, 84/124 (68%) were moderately differentiated, and 89/124 (72%) had bands or cords at the invasive front. Of the 124 patients with HNSCC, 84/124 (68%) demonstrated the presence of HPV, 0/124 (0%) was for oral squamous cell carcinomas (OSCC). HPV16 was the associated virus type in all positive samples. However, no significant association was observed between HPV positivity and other clinico-pathological variables including age and gender of the patients, stage, and malignancy differentiation. Conclusion: The results we provide suggest that HPV infection is low in HNSCC, in general, and absent in OSCC, specifically, in this UK population during this time period. This implies that HPV infection may not play an important role in HNSCC carcinogenesis compared to other risk factors in UK population. This information can aid in more effective treatment approaches for treating UK cases of HNSCC.

Spatial neglect treatment: The brain's spatial-motor Aiming systems.

Animal and human literature supports spatial-motor "Aiming" bias, a frontal-subcortical syndrome, as a core deficit in spatial neglect. However, spatial neglect treatment studies rarely assess Aiming errors. Two knowledge gaps result: spatial neglect rehabilitation studies fail to capture the impact on motor-exploratory aspects of functional disability. Also, across spatial neglect treatment studies, discrepant treatment effects may also result from sampling different proportions of patients with Aiming bias. We review behavioural evidence for Aiming spatial neglect, and demonstrate the importance of measuring and targeting Aiming bias for treatment, by reviewing literature on Aiming spatial neglect and prism adaptation treatment, and presenting new preliminary data on bromocriptine treatment. Finally, we review neuroanatomical and network disruption that may give rise to Aiming spatial neglect. Because Aiming spatial neglect predicts prism adaptation treatment response, assessment may broaden the ability of rehabilitation research to capture functionally-relevant disability. Frontal brain lesions predict both the presence of Aiming spatial neglect, and a robust response to some spatial neglect interventions. Research is needed that co-stratifies spatial neglect patients by lesion location and Aiming spatial neglect, to personalize spatial neglect rehabilitation and perhaps even open a path to spatial retraining as a means of promoting better mobility after stroke.

Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study.

BACKGROUND AND PURPOSE: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. METHODS: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. RESULTS: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. CONCLUSIONS: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

Impact of Delirium on Outcomes After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site. METHODS: We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site. RESULTS: Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3]). CONCLUSIONS: Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.