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Background: Despite recent advances in our knowledge of genetic contributions to the highly variable sickle cell disease (SCD) phenotype, our understanding of genetic factors associated with pain sensitivity in SCD remains limited. Previous studies investigated specific variants in single candidate genes and their association with SCD pain variability. The primary aim of the current study was to expand the genes and polymorphisms tested to discover new risk genes (polymorphisms) associated with central sensitization for individuals with SCD., Methods: Adults with sickle cell disease ( n = 59, Mage = 36.8 ± 11.5, 65.8 % female) underwent quantitative sensory testing to examine central sensitization and general pain sensitivity. Participants reported average crisis and non-crisis pain intensities weekly using a 0-100 scale, and provided salivary samples for genotyping. The Hardy-Weinberg equilibrium was verified for controls, and allele distributions were tested with chi-square and odds ratio tests. The Benjamini-Hochberg procedure was used to control for false discovery rate. Regression analyses and Wilcoxon tests were used to test associations for normally distributed and skewed data, respectively., Results: Central sensitization and general pain sensitivity were not associated with hemoglobin genotype (Ps > 0.05). Of 4145 SNPs tested, following false discovery rate adjustments, 11 SNPs (rs11575839, rs12185625, rs12289836, rs1493383, rs2233976, rs3131787, rs3739693, rs4292454, rs4364, rs4678, rs6773307) were significantly associated with central sensitization, and one SNP (rs7778077) was significantly associated with average weekly non-crisis pain. No SNPs were associated with general pain sensitivity., Conclusions: These findings provide insights into genetic variants association with average non-crisis pain and central sensitization for individuals with SCD, and may provide support for genetic predictors of heightened pain experience within SCD.

Background: Sickle cell disease (SCD) exemplifies many of the social, racial, and healthcare equity issues in the United States. Despite its high morbidity, mortality, and cost of care, SCD has not been prioritized in research and clinical teaching, resulting in under-trained clinicians and a poor evidence base for managing complications of the disease. This study aimed to perform a needs assessment, examining the perspectives of medical trainees pursuing hematology/oncology subspecialty training regarding SCD-focused education and clinical care., Method: Inductive, iterative thematic analysis was used to explore qualitative interviews of subspecialty hematology-oncology trainees' attitudes and preferences for education on the management of patients with SCD. Fifteen trainees from six programs in the United States participated in 4 focus groups between April and May 2023., Results: Thematic analysis resulted in 3 themes: 1. Discomfort caring for patients with SCD. 2. Challenges managing complications of SCD, and 3. Desire for SCD specific education. Patient care challenges included the complexity of managing SCD complications, limited evidence to guide practice, and healthcare bias. Skill-building challenges included lack of longitudinal exposure, access to expert clinicians, and didactics., Conclusions: Variations in exposure, limited formal didactics, and a lack of national standardization for SCD education during training contributes to trainees' discomfort and challenges in managing SCD, which in turn, contribute to decreased interest in entering the SCD workforce. The findings underscore the need for ACGME competency amendments, dedicated SCD rotations, and standardized didactics to address the gaps in SCD education., (© 2024. The Author(s).)

Background: Proactive psychiatric consultation services rapidly identify and assess medical inpatients in need of psychiatric care. In addition to more rapid contact, proactive services may reduce the length of stay and improve staff satisfaction. However, in some settings, it is impractical to integrate a proactive consultation service into every hospital unit; on-request and proactive services are likely to coexist in the future. Prior research has focused on changes in outcomes with the implementation of proactive services., Objective and Methods: This report describes differences between contemporary proactive and on-request services within the same academic medical center, comparing demographic and clinical data collected retrospectively from a 4-year period from the electronic medical record., Results: The proactive service saw patients over four times as many initial admissions (7592 vs. 1762), but transitions and handoffs between services were common, with 434 admissions involving both services, comprising nearly 20% of the on-request service's total contacts. The proactive service admissions had a shorter length of stay and a faster time to first psychiatric contact, and the patients seen were more likely to be female, of Black race, and to be publicly insured. There were over three times as many admissions to psychiatry from the proactive service. The on-request service's admissions had a longer length of stay, were much more likely to involve intensive care unit services, surgical services, and transfers among units, and the patients seen were more likely to die in the hospital or to be discharged to subacute rehabilitation., Conclusions: Overall, the results suggest that the two services fulfill complementary roles, with the proactive service's rapid screening and contact providing care to a high volume of patients who might otherwise be unidentified and underserved. Simultaneously, the on-request service's ability to manage patients in response to consult requests over a much larger area of the hospital provided important support and continuity for patients with complex health needs. Institutions revising their consultation services will likely need to consider the best balance of these differing functions to address perceived demand for services., (Copyright © 2024 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Mental illness is a common sickle cell disease (SCD) comorbidity. This observational study evaluated psychiatry appointment attendance among 137 young adults with SCD. In their first year of adult SCD care, 43% of subjects were referred to psychiatry. Referral was associated with chronic transfusion therapy. Twenty-four percent of subjects attended a psychiatry appointment; attendance was associated with the appointment being scheduled within 6 weeks of referral and no subject characteristics. Ninety-one percent of subjects attending psychiatry appointments had a psychiatric disorder. Among young adults with SCD, psychiatric morbidity is high. Psychiatric services are, therefore, essential for this patient population., (© 2024 Wiley Periodicals LLC.)

Depressive symptoms are prevalent in individuals living with sickle cell disease (SCD) and may exacerbate pain. This study examines whether higher depressive symptoms are associated with pain outcomes, pain catastrophizing, interference and potential opioid misuse in a large cohort of adults with SCD. The study utilized baseline data from the 'CaRISMA' trial, which involved 357 SCD adults with chronic pain. Baseline assessments included pain intensity, daily mood, the Patient Health Questionnaire (PHQ), the Generalized Anxiety Disorders scale, PROMIS Pain Interference, Pain Catastrophizing Scale, the Adult Sickle Cell Quality of Life Measurement Information System and the Current Opioid Misuse Measure. Participants were categorized into 'high' or 'low' depression groups based on PHQ scores. Higher depressive symptoms were significantly associated with increased daily pain intensity, negative daily mood, higher pain interference and catastrophizing, poorer quality of life and a higher likelihood of opioid misuse (all p < 0.01). SCD patients with more severe depressive symptoms experienced poorer pain outcomes, lower quality of life and increased risk of opioid misuse. Longitudinal data from this trial will determine whether addressing depressive symptoms may potentially reduce pain frequency and severity in SCD., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

A growing body of literature describes the use of buprenorphine for the treatment of chronic pain in people with sickle cell disease. The experiences of people with sickle cell disease who have tried buprenorphine have not yet reported. This qualitative descriptive study was conducted to explore perspectives on buprenorphine for chronic pain in sickle cell disease. We interviewed 13 participants with sickle cell disease who had been prescribed buprenorphine and had a clinic visit between December 1, 2020, and April 2022 in our Sickle Cell Center for Adults. Interviews were recorded, transcribed, and analyzed using thematic analysis. Eleven out of 13 participants were taking buprenorphine at the time of the interview, with a mean treatment duration of 33 months (SD 18, range 7-78 months). Five major themes were identified: 1) dissatisfaction with full agonist opioids; 2) navigating uncertainty with autonomy in deciding to try buprenorphine; 3) functional and relational changes after starting buprenorphine, 4) enduring systemic barriers to pain treatment, and 5) trusting treatment relationships are necessary when approaching patients about buprenorphine. The experience of adulthood living with sickle cell disease before and after starting buprenorphine is qualitatively different with significant improvements in social functioning. PERSPECTIVE: This study examined the experience of adults with sickle cell disease and chronic pain transitioning from full agonist opioids to buprenorphine. It is the first qualitative study of buprenorphine in people with sickle cell disease, contributing to a small but growing literature about buprenorphine and sickle cell disease., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Although descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about psychiatric illness prevalence, presentation, and treatment, particularly for adults. We provide a narrative review of what is known about common and debilitating psychiatric conditions such as depression, anxiety, and cognitive impairment, specifically for adults with SCD. We discuss the limitations of the current evidence, make provisional recommendations, and identify opportunities for research and improved care., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Chronic illness experiences often interfere with daily functioning (a concept known as illness intrusiveness) and health-related quality of life (HRQoL). However, less is known about the role of specific symptoms in predicting illness intrusiveness in sickle cell disease (SCD). This exploratory study examined associations between common SCD-related symptoms (i.e., pain, fatigue, depression, and anxiety), illness intrusiveness, and HRQoL among adults with SCD (n = 60). Illness intrusiveness significantly correlated with fatigue severity (r = .39, p = .002), depression severity (r = .45, p < .001), anxiety severity (r = .41, p = .001), physical HRQoL (r = - .53, p < .001), and mental HRQoL (r = - .44, p < .001). Multiple regression revealed a significant overall model, (R 2  = .28, F(4, 55) = 5.21, p = .001), with fatigue, but not pain, depression, or anxiety, significantly predicting illness intrusiveness (β = .29, p = .036). Results suggest that fatigue may be a primary factor contributing to illness intrusiveness-a determinant of HRQoL-in individuals with SCD. Given the limited sample size, larger confirmatory studies are warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: LHP is funded through the National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute (NHLBI; K23HL146841 and U01 HL156620–01), the American Society of Hematology, Doris Duke Charitable Foundation Grant (2020147), the Mellon Foundation, and Alexion and served as a consultant for Global Blood Therapeutics and Novo Nordisk. CPC serves as a consultant for DimeRx. SL receives research funding from Imara, Novartis, Global Blood Therapeutics, Takeda, CSL-Behring, Health Resources and Services Administration, Patient-Centered Outcomes Research Institiute and Maryland Community Health Resources Commission; consultancy for Bluebird bio, Novo Nordisk, Pfizer, and Magenta; and owns stock in Pfizer and Teva. AMA declares no competing interests. MH has research funding to the institution from Novo Nordisk, consultancy for Bluebird bio, and family member employment at Pfizer. ES has served as a consultant for Bluebird bio. KHMK is funded through NIH and NHLBI (1R33HL147845), Thalassemia Foundation Canada, Peter Munk Cardiac Centre, University of Toronto, Canadian Hematology Society, Agios Pharmaceuticals, and Pfizer and served as a consultant for Alexion Pharmaceuticals, Agios Pharmaceuticals, Bristol Myers Squibb, Forma Therapeutics, Pfizer, Novo Nordisk, and Vertex Pharmaceuticals. DSD serves as consultant for Pfizer, Novonordisk, Novartis, Agios Pharmaceuticals and Bluebird bio.

Introduction: Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings., Methods: One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics., Results: Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages., Discussion: Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rathke cleft cysts (RCCs) are common benign skull-base lesions arising from embryologic remnants of Rathke pouch. Though frequently asymptomatic, RCCs can become symptomatic because of compression of adjacent neural structures. Transcranial and neuroendoscopic surgical treatments have been described for symptomatic RCCs, but recurrence rates remain as high as 30%. Bioabsorbable steroid-eluting (BASE) stents significantly decrease adhesions and recurrent ostia obstruction after endoscopic sinus surgery. We sought to use BASE stents to aid marsupialization of symptomatic RCCs., Objective: To present long-term results of our initial experience with endoscopic-endonasal fenestration and placement of BASE stents for RCCs., Methods: Patients undergoing neuroendoscopic transsphenoidal fenestration of RCCs with BASE stent placement were identified and their medical records retrospectively reviewed., Results: Four patients underwent neuroendoscopic transsphenoidal fenestration and BASE stent placement from March 2016 to April 2018 for symptomatic RCCs. After the cyst contents were evacuated, a BASE stent was deployed in the cyst fenestration to prevent cyst wall regrowth or closure and facilitate marsupialization to the sphenoid sinus. No perioperative complications were encountered, and all patients reported symptom resolution by 2 weeks postoperatively. Postoperative endoscopic evaluation demonstrated epithelization of the cyst wall opening and patent marsupialization into the sphenoid sinus in all cases. After a mean follow-up of 56 ± 12 months, all patients remained asymptomatic with baseline visual function and no radiographic evidence of recurrence., Conclusion: Bioabsorbable steroid-eluting stent placement is a safe, facile, viable augmentation of neuroendoscopic technique for symptomatic RCCs with the potential to reduce long-term recurrence rates., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Chronic pain is a distinct complication that profoundly affects the lives of individuals with sickle cell disease (SCD). Chronic SCD pain emerges with increasing age and is very prevalent in adults. The pathophysiology of chronic SCD pain is likely distinct from acute SCD pain and therefore needs a different treatment approach. Clinical trials evaluating the treatment of chronic SCD pain are lacking and treatment currently relies on evidence from other chronic pain conditions. Continued investigations into the underlying causes of chronic SCD pain are needed, and clinical trials focused on chronic pain therapy are imperative., Competing Interests: Disclosure Neither Dr Carroll nor Dr Brandow has any conflicts to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The U.S. military requires medical readiness to support forward-deployed combat operations. Because time and distance to neurosurgical capabilities vary within the deployed trauma system, nonneurosurgeons are required to perform emergent cranial procedures in select cases. It is unclear whether these surgeons have sufficient training in these procedures., Methods: This quality-improvement study involved a voluntary, anonymized specialty-specific survey of active-duty surgeons about their experience and attitudes toward U.S. military emergency neurosurgical training., Results: Survey responses were received from 104 general surgeons and 26 neurosurgeons. Among general surgeons, 81% have deployed and 53% received training in emergency neurosurgical procedures before deployment. Only 16% of general surgeons reported participating in craniotomy/craniectomy procedures in the last year. Nine general surgeons reported performing an emergency neurosurgical procedure while on deployment/humanitarian mission, and 87% of respondents expressed interest in further predeployment emergency neurosurgery training. Among neurosurgeons, 81% had participated in training nonneurosurgeons and 73% believe that more comprehensive training for nonneurosurgeons before deployment is needed. General surgeons proposed lower procedure minimums for competency for external ventricular drain placement and craniotomy/craniectomy than did neurosurgeons. Only 37% of general surgeons had used mixed/augmented reality in any capacity previously; for combat procedures, most (90%) would prefer using synchronous supervision via high-fidelity video teleconferencing over mixed reality., Conclusions: These survey results show a gap in readiness for neurosurgical procedures for forward-deployed general surgeons. Capitalizing on capabilities such as mixed/augmented reality would be a force multiplier and a potential means of improving neurosurgical capabilities in the forward-deployed environments., (Published by Elsevier Inc.)

Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high-dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease (SCD) from full agonist opioids to buprenorphine using a method developed in the past 10 years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high-dose chronic opioid therapy (COT) with inadequate response, and often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are post-induction adverse events. There were seven adverse events in the first 3 days following standard induction, and two of which were judged to be definitely related to the induction but none with any lasting sequelae. At 6 months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the 6 months pre-induction to 2.89 (SD 3.40) in the 6 months post-induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to COT with early evidence of benefit for high-utilizing patients with SCD., (© 2022 Wiley Periodicals LLC.)

Background: How widely spreading depolarizations (SDs) propagate through the gyrencephalic brain, including sulci and deeper cortical areas, remains an important clinical question. Here, we investigated SDs that occur spontaneously after subarachnoid placement of autologous blood clots in sulci of the juvenile swine brain., Methods: To investigate the three-dimensional spread of waves, animals underwent continuous diffusion-weighted magnetic resonance imaging (DW-MRI) for up to 6 h following clot placement. SD is the mechanism of the cytotoxic edema of developing infarction that is diagnosed by DW-MRI, and DW-MRI also captures transient diffusion restriction caused by SD in less injured or healthy brains. Here, images (b = 0, 375, and 750) were acquired across five coronal slices with 1.25 × 1.25-mm in-plane resolution and 5-mm slice thickness, and the protocol was repeated every 6.83-9.15 s. Spatial drift correction, temporal smoothing, and signal intensity normalization were applied to generate videos of diffusion signal intensity changes for each coronal slice., Results: Review of video data from five animals revealed ten discrete events consisting of focal diffusion restriction that propagated through cerebral cortex. All events originated in the cortex surrounding the sulcal clot, either in the gyrus (n = 4) or in the sulcal depth (n = 6). In six cases, two to three independent waves spread simultaneously in medial, lateral, and antero-posterior directions. Waves traveled within sulcal walls, traversed the depths of sulci to re-emerge on the adjacent gyrus, and, in three cases, spread fully around the dorsolateral convexity. One event spread deep to olfactory regions along midline cortex, and no events were observed contralateral to the subarachnoid clot., Conclusions: Together, these results suggest that SDs in the injured gyrencephalic brain originate near the injury focus and can spread extensively through the cortex to wide and deep uninjured regions. These findings have implications for transient neurologic deficits in the neurocritically ill patient and relevance to patient monitoring and therapeutics., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: The Surviving Penetrating Injury to the Brain (SPIN) score utilizes clinical variables to estimate in-hospital and 6-month mortality for patients with civilian cranial gunshot wounds (cGSWs) and demonstrated good discrimination (area under the receiver operating characteristic curve [AUC] 0.880) in an initial validation study. The goal of this study was to provide an external, independent validation of the SPIN score for in-hospital and 6-month mortality., Methods: To accomplish this, the authors retrospectively reviewed 6 years of data from their institutional trauma registry. Variables used to determine SPIN score were collected, including sex, transfer status, injury motive, pupillary reactivity, motor component of the Glasgow Coma Scale (mGCS), Injury Severity Score (ISS), and international normalized ratio (INR) at admission. Multivariable logistic regression analysis identified variables associated with mortality. The authors compared AUC between models by using a nonparametric test for equality., Results: Of the 108 patients who met the inclusion criteria, 101 had all SPIN score components available. The SPIN model had an AUC of 0.962. The AUC for continuous mGCS score alone (0.932) did not differ significantly from the AUC for the full SPIN model (p = 0.26). The AUC for continuous mGCS score (0.932) was significantly higher compared to categorical mGCS score (0.891, p = 0.005). Use of only mGCS score resulted in fewer exclusions due to missing data. No additional variable included in the predictive model alongside continuous mGCS score was a significant predictor of inpatient mortality, 6-month mortality, or increased model discrimination., Conclusions: Given these findings, continuous 6-point mGCS score may be sufficient as a generalizable predictor of inpatient and 6-month mortality in patients with cGSW, demonstrating excellent discrimination and reduced bias due to missing data.

Regions of low oxygen (hypoxia) are found in >50% of breast tumours, most frequently in the more aggressive triple negative breast cancer subtype (TNBC). Metastasis is the cause of 90% of breast cancer patient deaths. Regions of tumour hypoxia tend to be more acidic and both hypoxia and acidosis increase tumour metastasis. In line with this the metastatic process is dependent on pH regulatory mechanisms. We and others have previously identified increased hypoxic expression of Na + driven bicarbonate transporters (NDBTs) as a major mechanism of tumour pH regulation. Hypoxia induced the expression of NDBTs in TNBC, most frequently SLC4A4 and SLC4A5. NDBT inhibition (S0859) and shRNA knockdown suppressed migration (40% reduction) and invasion (70% reduction) in vitro. Tumour xenograft metastasis in vivo was significantly reduced by NDBT knockdown. To investigate the mechanism by which NDBTs support metastasis, we investigated their role in regulation of phospho-signalling, epithelial-to-mesenchymal transition (EMT) and metabolism. NDBT knockdown resulted in an attenuation in hypoxic phospho-signalling activation; most notably LYN (Y397) reduced by 75%, and LCK (Y394) by 72%. The metastatic process is associated with EMT. We showed that NDBT knockdown inhibited EMT, modulating the expression of key EMT transcription factors and ablating the expression of vimentin whilst increasing the expression of E-cadherin. NDBT knockdown also altered metabolic activity reducing overall ATP and extracellular lactate levels. These results demonstrate that targeting hypoxia-induced NDBT can be used as an approach to modulate phospho-signalling, EMT, and metabolic activity and reduce tumour migration, invasion, and metastasis in vivo., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rape victims often face secondary victimization by the criminal justice system, prompting their advocates to promote a variety of procedural changes, including the provision of an independent legal counsel for victims. Sweden implemented a legal counsel for victims of sexual assault and rape in the late 1980s, yet research about their role remains limited. This article draws upon interviews with victim-lawyers in Sweden and suggests that having access to an independent legal counsel can mitigate the risks for secondary victimization by empowering victims to access their rights and providing emotional support and connectedness in the criminal justice system.

Objective: Postoperative telephone calls are a simple intervention that can be used to improve communication with patients, potentially affecting patient safety and satisfaction. Few studies in the neurosurgical literature have examined the effect of a postoperative telephone call on patient outcomes, although several exist across all surgical specialties. The authors performed a systematic review and analyzed studies published since 2000 to assess the effect of a postoperative telephone call or text message on patient safety and satisfaction across all surgical specialties., Methods: A search of PubMed-indexed articles was performed on June 12, 2021, and was narrowed by the inclusion criteria of studies from surgical specialties with > 50 adult patients published after 1999, in which a postoperative telephone call was made and its effects on safety and satisfaction were assessed. Exclusion criteria included dental, medical, and pediatric specialties; systematic reviews; meta-analyses; and non-English-language articles. Dual review was utilized., Results: Overall, 24 articles met inclusion criteria. The majority reported an increase in patient satisfaction scores after a postoperative telephone call was implemented, and half of the studies demonstrated an improvement in safety or outcomes., Conclusions: Taken together, these studies demonstrate that implementation of a postoperative telephone call in a neurosurgical practice is a feasible way to enhance patient care. The major limitations of this study were the heterogeneous group of studies and the limited neurosurgery-specific studies.

Background: Multiple device passes are associated with complications and poor functional outcomes following mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO)., Objective: To characterize the relationship between number of device passes, complications, angiographic outcomes, and clinical outcomes in MT for ELVO., Methods: This is a single-center, retrospective cohort study. Individual device passes for MT were evaluated for any change in Thrombolysis in Cerebral Infarction (TICI) score, successful revascularization (TICI 2b or 3), and complications. Outcomes were compared among groups requiring multiple passes with various cut-off points. Risk factors for unfavorable clinical outcome [90 day modified Rankin Scale > 2] were assessed using multivariate analysis., Results: Successful revascularization was achieved in 75% of 163 patients and 36% required only one device pass. After the second pass, the likelihood of angiographic improvement significantly decreased (p < 0.001). Using multiple cut-off points, higher post-procedural NIHSS scores, mortality rates, and unfavorable 90-day outcomes were associated with a greater number of passes. Multivariate analysis revealed ICA thrombus (comparison: M2, OR: 25, 95% CI 2-275, p = 0.01) and failed revascularization (OR: 68, 95% CI 3.12-1489, p = 0.01) as the only significant predictors of unfavorable clinical outcome. Nonetheless, the likelihood of favorable clinical outcome was higher in patients with an ICA occlusion who were revascularized in < 2 vs. ≥ 2 (44 vs 4%, p = 0.01) or < 3 vs. ≥ 3 (32 vs. 0%, p = 0.02) passes., Conclusion: The likelihood of angiographic improvement in patients with ELVO significantly decreases after the second pass. A greater number of passes is associated with worsened clinical outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Since its initial description in 1957 as an idiopathic disease, moyamoya disease has proved challenging to treat. Although the basic pathophysiology of this disease involves narrowing of the terminal carotid artery with compensatory angiogenesis, the molecular and cellular mechanisms underlying these changes are far more complex. In this article, the authors review the literature on the molecular and cellular pathophysiology of moyamoya disease with an emphasis on potential therapeutic targets.

Background: There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption., Purpose: We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex., Methods: Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants' awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime., Results: Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women., Conclusion: These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The worldwide COVID-19 pandemic poses challenges to healthcare capacity and infrastructure. The authors discuss the structure and efficacy of the U.S. Navy's response to COVID-19 and evaluate the utility of this endeavor, with the objective of providing future recommendations for managing worldwide healthcare and medical operational demands from the perspective of Navy Neurosurgery., Materials and Methods: The authors present an extensive review of topics and objectively highlight the efforts of U.S. Navy Neurosurgery as it pertains to the humanitarian mission during the COVID-19 pandemic., Results: During the humanitarian mission (March 27, 2020-April 14, 2020), the response of active duty and reserve neurosurgeons in the U.S. Navy was robust. Neurosurgical coverage was present on board the U.S. Navy Ships Mercy and Comfort, with additional neurosurgical deployment to New York City for intensive care unit management and coverage., Conclusions: The U.S. Navy neurosurgical response to the COVID-19 pandemic was swift and altruistic. Although neurosurgical pathologies were limited among the presenting patients, readiness and manpower continue to be strong influences within the Armed Forces. The COVID-19 response demonstrates that neurosurgical assets can be rapidly mobilized and deployed in support of wartime, domestic, and global humanitarian crises to augment both trauma and critical care capabilities., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: How personality traits, anxiety, and depressive disorders relate longitudinally has implications for etiologic research and prevention. We sought to determine how neuroticism and extraversion relate to first-onset anxiety and depressive disorders in young adults., Design: An inception cohort of 489 university freshmen was followed for 6 years., Method: Participants self-reported personality traits using the Eysenck Personality Questionnaire. Anxiety and depressive disorders were assessed using the Diagnostic Interview Schedule., Results: Baseline neuroticism predicted first-onset panic disorder, agoraphobia, generalized anxiety disorder (GAD), and major depressive disorder (MDD), while introversion predicted first-onset agoraphobia (moderate-large effects). Participants who developed panic disorder, agoraphobia, GAD, or MDD had increases in neuroticism if the disorder was current at follow-up (moderate-large effects). Participants who developed MDD but were in remission by follow-up had a moderate increase in neuroticism., Conclusions: High neuroticism in young adulthood is either a true risk factor, or marker of risk, for first-onset anxiety and depressive disorders, as is low extraversion for agoraphobia. The current data suggest large neuroticism "state" effects for panic disorder, agoraphobia, and MDD, and moderate "scar" effects from MDD. Though many clinicians and researchers regard personality traits simply as "vulnerability" factors, longitudinal analyses suggest additional complexity.

Absence of formal and systematic screening for mood and anxiety disorders among patients with sickle cell disease (SCD) can result in under-recognized psychological problems. This study examined the prevalence of psychological symptoms using a systematic screening process. Patients with SCD completed four self-report screening tools for measurement of depressive and anxiety symptoms, self-efficacy, and pain. The goal was to detect patients with psychological symptoms and identify predictors of follow-up treatment attendance. A total of 336 adult patients (57% female, mean age 33 years) completed validated screening instruments for major depressive disorder and generalized anxiety disorder. Patients recommended for mental health follow-up included higher proportions of women. Patients who accepted the mental health follow up had higher levels of education compared to groups that did not accept nor attend the follow-up appointment. Overall, 34% of patients who endorsed elevated distress scores and were referred for mental health care attended the follow-up appointment. Findings suggest patients with SCD and elevated psychological distress are likely to use mental health treatment resources, which notes this program's success in identifying needs and responding to them. However, further research is needed to understand ways to engage this population in mental health care.

Background: The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care., Objective: These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD., Methods: ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment., Results: The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery., Conclusions: Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions., (© 2020 by The American Society of Hematology.)

In spite of the developing endovascular era, large (15-25 mm) and giant (>25 mm) wide-neck cerebral aneurysms remained technically challenging. Intracranial flow-diverting stents (FDS) were developed to address these challenges by targeting aneurysm hemodynamics to promote aneurysm occlusion. In 2011, the first FDS approved for use in the United States market. Shortly thereafter, the Pipeline of Uncoilable or Failed Aneurysms (PUFS) study was published demonstrating high efficacy and a similar complication profile to other intracranial stents. The initial FDA instructions for use (IFU) limited its use to patients 22 years old or older with wide-necked large or giant aneurysms of the internal carotid artery (ICA) from the petrous segment to superior hypophyseal artery/ophthalmic segment. Expanded IFU was tested in the Prospective Study on Embolization of Intracranial Aneurysms with PipelineTM Embolization Device (PREMIER) trial. With further post-approval clinical data, the United States FDA expanded the IFU to include patients with small or medium, wide-necked saccular or fusiform aneurysms from the petrous ICA to the ICA terminus. However, IFU is more restrictive in South Korea than in United States. Several systematic reviews and meta-analyses have sought to evaluate the overall efficacy of FDS for the treatment of cerebral aneurysms and consistently identify FDS as an effective technique for the treatment of aneurysms broadly with complication rates similar to other traditional techniques. A growing body of literature has demonstrated high efficacy of FDS for small aneurysms; distal artery aneurysms; non-saccular aneurysms posterior circulation aneurysms and complication rates similar to traditional techniques. In the short interval since the Pipeline Embolization Device was first introduced, FDS has been firmly entrenched as a powerful tool in the endovascular armamentarium. As new FDS are developed, established FDS are refined, and delivery systems are improved the uses for FDS will only expand further. Researchers continue to work to optimize the mechanical characteristics of the FDS themselves, aiming to optimize deploy ability and efficacy. With expanded use for small to medium aneurysms and posterior circulation aneurysms, FDS technology is firmly entrenched as a powerful tool to treat challenging aneurysms, both primarily and as an adjunct to coil embolization. With the aforementioned advances, the ease of FDS deployment will improve and complication rates will be further minimized. This will only further establish FDS deployment as a key strategy in the treatment of cerebral aneurysms.

Sickle cell disease is a uniquely complex painful disease, with lifelong episodes of unpredictable acute pain and superimposed chronic pain in adulthood. Both painful crises and chronic pain in sickle cell disease lack strong objective pathological correlates and their mechanisms are poorly understood. Opioids have emerged as the standard of care for severe acute pain in sickle cell disease and many patients with chronic pain are maintained on chronic opioid therapy. The strong association between recurrent acute pain and chronic pain in SCD blurs the distinction between acute and chronic opioid management paradigms. In addition, opioid management for SCD is dogged by stigma and concerns regarding addiction. This review aims to synthesize the broad literature on opioids to highlight the clinical complexity of opioid management in sickle cell disease and suggest directions for future research and clinical innovation., (Copyright © 2019. Published by Elsevier B.V.)

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Objective: Recent studies have shown an association between proactive psychiatric consultation on medical units and shorter length of stay. The aim of this study was to assess the impact of implementing a proactive psychiatric consult service on general medical units in an urban teaching hospital on length of stay and qualitative measurement of satisfaction of adequacy of psychiatric services., Methods: Bivariate and multivariate analyses of demographic, clinical and outcome data were performed comparing patients seen by the proactive psychiatric consult team, patients seen contemporaneously on other general medical units by a traditional, reactive consult team and patients seen the prior year on the proactive intervention units by the reactive consult team. Length of stay was the primary outcome examined. Regression modeling was performed to assess further the relationship of length of stay with the three groups. Nursing and physician staff were queried before and after intervention regarding satisfaction with psychiatric resources on the intervention units., Results: Patients seen by the proactive team had shorter length of stay than those seen by contemporaneous reactive consult team (p = 0.005) or the prior year by the reactive team on the intervention units (p = 0.005). There was no significant difference between the latter two groups. Time to consult was also shorter for patients seen through the proactive model than the reactive model on other units at the same time (0.01) or the preceding year (<0.001). Nursing and physician satisfaction with psychiatric help increased significantly in three of four measures., Conclusions: Proactive psychiatric consultation in our study correlated with shorter time to consult, shorter length of stay, and improved staff satisfaction compared to a reactive consult model., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Hydroxyurea (HU) is a drug that targets the underlying pathophysiology of sickle cell disease (SCD); however, it continues to be an underutilized treatment for adults. Previous research suggests that HU treatment can result in fewer hospital contacts for acute vaso-occlusive pain crises (VOC). Hydroxyurea's impact on non-VOC pain, however, is not well established., Objectives: This study examined whether HU moderated patterns of static and dynamic pain processing and clinical pain in SCD individuals., Methods: Fifty-eight patients with SCD (N taking HU = 17) underwent quantitative sensory testing (QST) and completed twice daily symptom diaries for 12 weeks. Quantitative sensory testing established thermal threshold and tolerance, mechanical thresholds, and thermal and mechanical temporal summation of pain., Results: Groups did not differ in age, sex, or opioid use. After controlling for morphine use, QST results showed that participants taking HU had higher heat and mechanical pain thresholds (static QST measures) but not thermal and mechanical temporal summation (dynamic QST measures). Participants taking HU also reported lower VOC pain compared with SCD participants not taking HU; however, HU did not moderate non-VOC clinical pain ratings., Conclusion: Findings cautiously suggest that HU acts on pain hypersensitivity and VOC pain, rather than inhibiting pain facilitation and non-VOC pain. These differences may reflect HU's influence on peripheral rather than central sensitization. Future research is warranted to replicate these findings in a larger sample and determine whether early HU administration can prevent peripheral sensitization in SCD individuals., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Military neurosurgery has played an integral role in the development and innovation of neurosurgery and neurocritical care in treating battlefield injuries. It is of paramount importance to continue to train and prepare the next generation of military neurosurgeons. For the Army, this is currently primarily achieved through the military neurosurgery residency at the National Capital Consortium and through full-time out-service positions at the Veterans Affairs-Department of Defense partnerships with the University of Florida, the University of Texas-San Antonio, and Baylor University. The authors describe the application process for military neurosurgery residency and highlight the training imparted to residents in a busy academic and level I trauma center at the University of Florida, with a focus on how case variety and volume at this particular civilian-partnered institution produces neurosurgeons who are prepared for the complexities of the battlefield. Further emphasis is also placed on collaboration for research as well as continuing education to maintain the skills of nondeployed neurosurgeons. With ongoing uncertainty regarding future conflict, it is critical to preserve and expand these civilian-military partnerships to maintain a standard level of readiness in order to face the unknown with the confidence befitting a military neurosurgeon.

Despite its rarity in the United States, sickle cell disease accounts for a disproportionate amount of healthcare utilization and costs. The majority of this is due to acute care for painful crises. A small subpopulation of patients accounts for most these costs due to frequent visits to emergency departments and acute care facilities. Previous investigations have found that these high utilizing patients are distinguished by both a more severe disease course and certain non-hematologic characteristics, which may include higher socioeconomic status and some psychiatric and psychological characteristics. This prospective observational cohort study was undertaken to test the ability of these characteristics to prospectively predict acute pain care outcomes, including visit frequency, total opioid doses, and pain improvement at the Johns Hopkins Sickle Cell Infusion Center (SCIC). Seventy-three participants were followed for 12 months and SCIC utilization and treatment outcomes were tabulated for 378 visits. Participants who visited the SCIC most frequently had markedly worse pain improvement despite higher within-visit opioid doses. Higher utilization was associated with indicators of greater illness severity, more aggressive treatment for sickle cell disease, higher baseline opioid doses, higher socioeconomic status, greater pain-related anxiety, and a history of psychiatric treatment. Overall, poor acute pain treatment response was associated with higher utilization and higher baseline opioid doses. The pattern of association between high utilization, poor acute care outcomes, and higher baseline opioid doses is discussed in terms of prior research and future directions., (© 2018 Wiley Periodicals, Inc.)

Background: Patients with mild to moderate traumatic brain injury (TBI) are often primarily managed by emergency medicine and trauma/acute care physicians. The Brain Injury Guidelines (BIG) were developed at an American College of Surgeons-accredited Level 1 trauma center to triage mild to moderate TBI patients and help identify patients who warrant neurosurgical consultation. The BIG have not been validated at a Level III trauma center. We hypothesized that BIG criteria can be safely adapted to an American College of Surgeons-accredited Level III trauma center to guide transfers to a higher echelon of care., Methods: We reviewed the trauma registry at a Level III trauma center to identify TBI patients who presented with an Abbreviated Injury Severity-Head score greater than zero. Demographic data, injury details, and clinical outcomes were abstracted with primary outcome measures of worsening on second computed tomography of the head, neurosurgical intervention, transfer to a Level I trauma center, and in-hospital mortality. Patients were classified using the BIG criteria. After validating the BIG in our cohort, we reclassified patients using updated BIG criteria. Updated criteria included mechanism of injury, reclassification of anticoagulation or antiplatelet use, and replacement of the neurologic examination component with stratification by admission Glasgow Coma Scale (GCS) score., Results: From July 2013 to June 2016, 332 TBI patients were identified: 115 BIG-1, 25 BIG-2, and 192 BIG-3. Patients requiring neurosurgical intervention (n = 30) or who died (n = 29) were BIG-3 with one exception. Patients with GCS score of less than 12 had worse outcomes than those with a GCS score of 12 or greater, regardless of BIG classification. Anticoagulant or antiplatelet use was not associated with worsened outcomes in patients not meeting other BIG-3 criteria. The updated BIG resulted in more patients in BIG-1 (n = 109) and BIG-2 (n = 100) without negatively affecting outcomes., Conclusion: The BIG can be applied in the Level III trauma center setting. Updated BIG criteria can aid triage of mild to moderate TBI patients to a Level I trauma center and may reduce secondary overtriage., Level of Evidence: Care management, level IV.

Chronic opioid therapy is a common treatment regimen for patients with sickle cell disease (SCD), a chronically painful recessive hemoglobinopathy. The collective risk profile of chronic opioid therapy necessitates an understanding of which pain-related factors, such as affect and pain catastrophizing, are associated with the ebbs and flows of opioid use in daily life, a topic that has received very little attention among patients with any type of chronically painful condition, including SCD. We therefore investigated the variability of day-to-day patterns of short- and long-acting opioid use and their associations with pain and pain-related cognitive and affective processes in daily life among patients with SCD using a nightly electronic diary (N = 45). Opioid use was self-reported and converted into oral morphine equivalents for analysis, which was conducted with mixed effects modeling. Results indicated that greater pain and pain catastrophizing were associated with greater use of short-acting opioids, and negative affect was associated with greater use of long-acting opioids. Additionally, the association of pain and short-acting opioid use was moderated by pain catastrophizing, showing that opioid use was elevated when patients catastrophized about their pain, even if they reported low levels of pain. These findings suggest that monitoring pain-related cognitive and affective variables may be a useful approach to understanding risk for problematic opioid use in patients with daily pain., Perspective: The present study shows that pain and pain-related cognitive and affective variables are associated with daily variation in prescription opioid use in SCD. The findings may have broad implications for tracking and defining risk for prescription opioid misuse in patients with daily pain., (Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.)

See Ghoshal and Claassen (doi:10.1093/brain/awx226) for a scientific commentary on this article. Early cortical infarcts are common in poor-grade patients after aneurysmal subarachnoid haemorrhage. There are no animal models of these lesions and mechanisms are unknown, although mass cortical spreading depolarizations are hypothesized as a requisite mechanism and clinical marker of infarct development. Here we studied acute sequelae of subarachnoid haemorrhage in the gyrencephalic brain of propofol-anaesthetized juvenile swine using subdural electrode strips (electrocorticography) and intraparenchymal neuromonitoring probes. Subarachnoid infusion of 1–2 ml of fresh blood at 200 µl/min over cortical sulci caused clusters of spreading depolarizations (count range: 12–34) in 7/17 animals in the ipsilateral but not contralateral hemisphere in 6 h of monitoring, without meaningful changes in other variables. Spreading depolarization clusters were associated with formation of sulcal clots (P < 0.01), a high likelihood of adjacent cortical infarcts (5/7 versus 2/10, P < 0.06), and upregulation of cyclooxygenase-2 in ipsilateral cortex remote from clots/infarcts. In a second cohort, infusion of 1 ml of clotted blood into a sulcus caused spreading depolarizations in 5/6 animals (count range: 4–20 in 6 h) and persistent thick clots with patchy or extensive infarction of circumscribed cortex in all animals. Infarcts were significantly larger after blood clot infusion compared to mass effect controls using fibrin clots of equal volume. Haematoxylin and eosin staining of infarcts showed well demarcated zones of oedema and hypoxic-ischaemic neuronal injury, consistent with acute infarction. The association of spreading depolarizations with early brain injury was then investigated in 23 patients [14 female; age (median, quartiles): 57 years (47, 63)] after repair of ruptured anterior communicating artery aneurysms by clip ligation (n = 14) or coiling (n = 9). Frontal electrocorticography [duration: 54 h (34, 66)] from subdural electrode strips was analysed over Days 0–3 after initial haemorrhage and magnetic resonance imaging studies were performed at ∼ 24–48 h after aneurysm treatment. Patients with frontal infarcts only and those with frontal infarcts and/or intracerebral haemorrhage were both significantly more likely to have spreading depolarizations (6/7 and 10/12, respectively) than those without frontal brain lesions (1/11, P’s < 0.05). These results suggest that subarachnoid clots in sulci/fissures are sufficient to induce spreading depolarizations and acute infarction in adjacent cortex. We hypothesize that the cellular toxicity and vasoconstrictive effects of depolarizations act in synergy with direct ischaemic effects of haemorrhage as mechanisms of infarct development. Results further validate spreading depolarizations as a clinical marker of early brain injury and establish a clinically relevant model to investigate causal pathologic sequences and potential therapeutic interventions.

Background: The use of anticoagulants or antiplatelet medications has become increasingly common and is a well-established risk factor for worsening of hemorrhages in trauma patients. The current study addresses the need to investigate the efficacy of point-of-care tests (POC) as an adjunct to conventional coagulation testing in traumatic brain injury (TBI) patients., Methods: A retrospective review of 190 TBI patients >18 years of age who underwent both conventional and POC testing as part of their admission coagulopathy workup was conducted. Coagulation deficiency was defined as an international normalized ratio (INR) >1.4, a reaction time (r-value) on rapid thromboelastography >50 seconds, or a VerifyNow Aspirin (VN-ASA) level of < 550 Aspirin Reaction Units., Results: Among 190 patients, 91 (48%) disclosed a history of either warfarin or antiplatelet use or had documented INR >1.4. Of the 18 (9%) patients who reported warfarin use, 83% had elevated INR and 61% had elevated r-value. However, 41% of the patients without reported anticoagulant usage revealed significantly elevated r-value consistent with a post-traumatic hypocoagulable state. Of 64 (34%) patients who reported taking ASA, 51 (80%) demonstrated therapeutic VN-ASA. Interestingly, 31 of 126 (25%) patients not reporting ASA use were also noted to have therapeutic VN-ASA suggestive of platelet dysfunction., Conclusions: The coagulopathy POC panel consisting of r-TEG and VN-ASA successfully identified a subset of TBI patients with an occult coagulopathy that would have otherwise been missed. Standardization of these POC assays on admission in TBI may help guide patient resuscitation in the acute setting., Competing Interests: There are no conflicts of interest.

During the past 20 years, the traditional supportive treatment for stroke has been radically transformed by advances in catheter technologies and a cohort of prominent randomized controlled trials that unequivocally demonstrated significant improvement in stroke outcomes with timely endovascular intervention. However, substantial limitations to treatment remain, among the most important being timely access to care. Nonetheless, stroke care has continued its evolution by incorporating technological advances from various fields that can further reduce patients' morbidity and mortality. In this paper the authors discuss the importance of emerging technologies-mobile stroke treatment units, telemedicine, and robotically assisted angiography-as future tools for expanding access to the diagnosis and treatment of acute ischemic stroke.

Objective: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain., Methods: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory., Results: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain., Discussion: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology.

Catastrophizing is a potent psychological modulator of pain across several chronic pain populations; yet despite evidence that patients with sickle cell disease (SCD) catastrophize more than patients with other chronic pain conditions, previous research indicates that catastrophizing is not related to sickle cell pain after controlling for relevant covariates such as depression. Recent research suggests that pain-related catastrophizing should be assessed across pain contexts (eg, dispositional and situational). In this study, we measured disease-specific, general non-disease-related, and situational catastrophizing and assessed the relationship between these contextual dimensions of catastrophizing and laboratory and clinical pain among patients with SCD. Results revealed differential catastrophizing across pain contexts, with patients reporting greater catastrophizing about SCD-specific pain compared with non-SCD pain and laboratory pain. SCD-specific and non-SCD catastrophizing were associated with clinical pain outcomes, and situational catastrophizing with markers of central sensitization and laboratory pain. Further examination of the time course of laboratory responses revealed that increases in situational catastrophizing were associated with subsequent increases in laboratory pain sensitivity. Taken together, results show the relevance of catastrophizing in understanding pain in SCD, and suggest that context-specific anchors may be beneficial in predicting different aspects of the pain experience (eg, chronic pain, pain sensitization)., Perspective: Patients with SCD report greater catastrophizing about sickle cell-specific pain relative to other pains. Disease-specific and non-disease-related pain catastrophizing were associated with clinical pain, and situational catastrophizing predictive of subsequent laboratory pain. Evaluation of context-specific catastrophizing may more accurately predict different aspects of the pain experience., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Sickle cell disease (SCD) is associated with high healthcare utilization rates and poor outcomes in a subset of patients, although the underlying factors that predict this phenotype are poorly understood. Prior studies suggest that comorbid avascular necrosis (AVN) contributes to high healthcare utilization. We sought to clarify whether AVN independently predicts acute care utilization in adults with SCD and to identify characteristics of those with AVN that predict higher utilization., Methods: We reviewed the medical records of 87 patients with SCD with symptomatic AVN and compared acute care utilization and clinical characteristics with 87 sex- and age-matched patients with SCD without symptomatic AVN. Patients with ≥2 years of follow-up were included. Outcomes were compared using bivariate analysis and multivariate regression., Results: Our study included 1381 follow-up years, with a median of 7 years per patient. The AVN cohort had greater median rates of urgent care visits (3.2/year vs 1.3/year; P = 0.0155), admissions (1.3/year vs 0.4/year; P = 0.0002), and admission days (5.1 days/year vs 1.8 days/year; P = 0.0007). History of high utilization (odds ratio [OR] 4.28; P = 0.001), acute chest syndrome (OR 3.12; P = 0.005), pneumonia (OR 3.20; P = 0.023), hydroxyurea therapy (OR 2.23; P = 0.0136), and long-term transfusion (OR 2.33; P = 0.014) were associated with AVN. In a median regression model, AVN, acute chest syndrome, and pneumonia were independently associated with greater urgent care visits and admissions., Conclusions: Symptomatic AVN was found to be an independent risk factor for acute care utilization in patients with SCD. Because this is a potentially modifiable factor, further studies are urgently needed to determine whether AVN prevention/early treatment interventions will alter utilization and improve outcomes for patients with SCD.

Objectives: Sickle cell disease (SCD) is associated with a high level of emergency department and hospital utilization, as well as a high rate of hospital readmissions. At Johns Hopkins Hospital, as at other institutions, SCD accounts for a large proportion of readmissions. Our study examined patient and hospitalization factors involved in readmissions at Johns Hopkins Hospital., Methods: Patients at the Johns Hopkins Sickle Cell Center for Adults with a readmission in fiscal year 2011 were compared with an age- and sex-matched sample of clinic patients for comorbidities, complications, and prior utilization. Hospitalizations that were followed by readmissions were compared with those that were not as to admitting service, length of stay, and average daily opioid dose., Results: Patients with readmissions had more complications and comorbidities and much higher prior utilization than typical clinic patients, whereas hospitalizations that were followed by readmissions had a longer length of stay but similar opioid doses., Conclusions: For patients with SCD with a high volume of hospital use, readmissions may be a natural consequence of a high-admission frequency associated with greater disease severity and higher comorbidity.

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with low educational attainment may be at increased risk for unplanned health care utilization. This study aimed to determine what factors are related to emergency department (ED) visits in hopes of guiding treatments and early interventions., Methods: At two medical centers in the Mid-Atlantic United States, 258 adults with sickle cell disease aged 19-70 years participated in a retrospective study where we examined whether education level is independently associated with ED visits after accounting for other socioeconomic status (SES) variables, such as pain and disease severity and psychosocial functioning., Results: The data showed that patients without a high school education visited the ED three times as frequently as patients with post secondary education. Controlling for poverty and employment status decreased the effect of education on ED visits by 33.24 %. Further controlling for disease severity and/or psychosocial functioning could not account for the remaining association between education and ED visits, suggesting that education is independently associated with potentially avoidable emergency care., Conclusions: Early interventions addressing disparities in academic performance, especially for those children most at risk, may lead to improved long-term health outcomes in this population.