"The project did not come to us with a solution": Perspectives of research teams on implementing a study about electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease.

BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. RESULTS: A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. CONCLUSIONS: Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED.

Utility of illness symptoms for predicting COVID-19 infections in children.

BACKGROUND: The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend that symptomatic children remain home and get tested to identify potential coronavirus disease 2019 (COVID-19) cases. As the pandemic moves into a new phase, approaches to differentiate symptoms of COVID-19 versus other childhood infections can inform exclusion policies and potentially prevent future unnecessary missed school days. METHODS: Retrospective analysis of standardized symptom and exposure screens in symptomatic children 0-18 years tested for SARS-CoV-2 at three outpatient sites April to November 2020. Likelihood ratios (LR), number needed to screen to identify one COVID-19 case, and estimated missed school days were calculated. RESULTS: Of children studied (N = 2,167), 88.9% tested negative. Self-reported exposure to COVID-19 was the only factor that statistically significantly increased the likelihood of a positive test for all ages (Positive LR, 5-18 year olds: 5.26, 95% confidence interval (CI): 4.37-6.33; 0-4 year olds: 5.87, 95% CI: 4.67-7.38). Across ages 0-18, nasal congestion/rhinorrhea, sore throat, abdominal pain, and nausea/vomiting/diarrhea were commonly reported, and were either not associated or had decreased association with testing positive for COVID-19. The number of school days missed to identify one case of COVID-19 ranged from 19 to 48 across those common symptoms. CONCLUSIONS: We present an approach for identifying symptoms that are non-specific to COVID-19, for which exclusion would likely lead to limited impact on school safety but contribute to school-days missed. As variants and symptoms evolve, students and schools could benefit from reconsideration of exclusion and testing policies for non-specific symptoms, while maintaining testing for those who were exposed.

Deep brain stimulation of the subthalamic nucleus alters frontal activity during spatial working memory maintenance of patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.

Transient Horizontal Gaze Palsy in a One-Month-Old Boy after a Fall.

A 1-month-old boy was evaluated after a fall from a height of 3 feet and found to have right parietal skull fracture as well as right and left frontal traumatic hemorrhage. Ten days after the injury, he represented with a persistent left gaze preference. Further workup including MRI and EEG determined that this finding was most likely due to a small, focal, left-frontal eye field lesion. We review the horizontal gaze pathway and demonstrate that this is present at this very young age, and that a very focal and relatively minor injury can cause gaze disturbance.

Recruitment Strategies in the Integration of Mobile Health Into Sickle Cell Disease Care to Increase Hydroxyurea Utilization Study (meSH): Multicenter Survey Study.

BACKGROUND: Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. OBJECTIVE: The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. METHODS: Recruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. RESULTS: Total enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001). CONCLUSIONS: We found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319.

Ventricular width and complicated recovery following deep brain stimulation surgery.

BACKGROUND: Candidates for deep brain stimulation (DBS) must be carefully evaluated to balance expected benefits with the possibility of serious complications. Several predictive factors exist but are imperfect. OBJECTIVES: The aim of this study was to determine whether linear measurements of the lateral ventricles predict complications following DBS. METHODS: We retrospectively studied a cohort of DBS patients. The primary outcome was postoperative confusion; secondary outcomes were discharge disposition and all in-hospital complications. For each case, a control matched for age, sex, diagnosis, and DBS target was identified. Linear measurements were made from routine preoperative axial MRIs for both cases and controls. RESULTS: A total of 40 patients met one or more of the end points. Patients with postoperative confusion had a significantly larger minimum width of the lateral ventricles than controls. Patients discharged to a higher level of care and those with any complications also had significantly greater maximum and minimum ventricular widths than controls. CONCLUSIONS: These results suggest that preoperative measurement of the maximum and minimum width of the lateral ventricles may help predict which patients are at risk for complicated recoveries following DBS.

Teaching Death Disclosure: A Mixed-Method Comparison of Resident Self-Assessment and Standardized Patient Assessment.

OBJECTIVE: To characterize how pediatric resident self-evaluation compares to standardized patient evaluations in simulated child death disclosure scenarios. METHODS: This was a prospective, observational, mixed-methods study in which 18 second-year pediatric residents delivered the news of a death of a child to a trained standardized patient (SP) couple. The SPs evaluated residents via a quantitative global rating (1-3 scale) and via qualitative comments. Following the training, the residents completed self-assessments consisting of a global rating, qualitative comments, and their confidence related to 5 death disclosure skills. RESULTS: Agreement between SPs and resident ratings was poor; resident scores were compared to each of their 2 SP evaluators yielding Kappa coefficients of -0.23 (95% confidence interval = -0.60 to -0.07) and -0.30 (95% confidence interval = -0.70 to -0.04). Residents uniformly rated themselves as less capable in their communication skills than SPs did. Residents reported significant increases in their confidence in discussing autopsy and organ donation. Major themes determined from the qualitative comments from SPs included nonverbal communication, verbal communication, attunement to parents, and management of next steps. Residents' comments mirrored these themes with the exception of the absence of nonverbal communication. CONCLUSIONS: Pediatric residents underestimated their abilities in a self-assessment of their performance in a SP death disclosure scenario, demonstrating the importance of external feedback, particularly from SPs themselves. Based on SP feedback, future death disclosure trainings should emphasize nonverbal communication skills and specific behaviors that convey effective attunement to families.

Impact of Teaching Sexual Health Education on Medical Students.

BACKGROUND AND OBJECTIVES: Physician discomfort, embarrassment, and perceived lack of time and/or training all play a role in preventing physicians from discussing sexual health with patients. Past research shows this discomfort begins in medical school. We aimed to determine whether teaching sexual health education increases medical students' self-efficacy in discussing sexual health topics with adolescents. METHODS: We emailed a retrospective pre/postsurvey to all medical students who taught sexual health education in a local middle school through Sex Ed by Brown Med (N=61). RESULTS: Participation in Sex Ed by Brown Med improves self-efficacy in discussing nine sexual health topics and in performing nine advanced interviewing skills relevant to sexual health in a retrospective analysis using self-reported data. CONCLUSIONS: Programs similar to Sex Ed by Brown Med may be useful in improving medical students' ability to adequately care for their patients' sexual health by making future clinicians more comfortable when discussing the important topic of sexuality, and concurrently providing evidence-based comprehensive sexual health education to middle school students. Further research is needed to determine the impact of our program (and similar programs) before disseminating this model of sexual education.

A new inner-city specialist programme reduces readmission rates in frequently admitted patients with bipolar disorder.

Aims and methodThe OPTIMA mood disorders service is a newly established specialist programme for people with bipolar disorder requiring frequent admissions. This audit compared data on hospital admissions and home treatment team (HTT) spells in patients before entry to and after discharge from the core programme. We included patients admitted between April 2015 and March 2017 who were subsequently discharged. Basic demographic data and numbers of admissions and HTT spells three years before and after discharge were collected and analysed. RESULTS: Thirty patients who completed the programme were included in the analyses. The median monthly rate of hospital admissions after OPTIMA was significantly reduced compared with the rate prior to the programme. HTT utilisation was numerically reduced, but this difference was not statistically significant.Clinical implicationsThese results highlight the effectiveness and importance of individually tailored, specialist care for patients with bipolar disorder following discharge from hospital.Declaration of interestNone.

A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination.

Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)-modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.

Effects of chronic alcohol consumption on long-term outcomes of thalamic deep brain stimulation for essential tremor.

The prevalence of essential tremor (ET) is about 4% above 40years of age. Chronic alcohol consumption is present in around 20% of patients with ET. Our objective was to identify whether chronic alcohol consumption was associated with a negative effect on tremor outcome after thalamic deep brain stimulation (DBS) in ET patients. We conducted a retrospective chart review, from January 2005 to December 2012, from which 23 patients who had ventral intermediate nucleus (Vim)-DBS surgery for ET were identified. Seven patients had a positive history of chronic alcohol consumption. We defined as chronic alcohol users those patients with a habit of drinking alcohol every day in order to suppress tremor. In the overall group of 23 patients, there was a reduction in the median tremor score from 8 pre-operatively, to 1 post-operatively (p<0.0001). The alcohol consumers group experienced a reduction in the median tremor score from 6 pre-operatively to 0 post-operatively (p=0.03). The non-alcohol consumers group had a reduction in the median tremor score from 8 pre-operatively to 1.7 post-operatively (p<0.0001). Both groups of patients experienced significant benefit from thalamic DBS. A larger study may reveal statistically significant differences between subgroups.

Basic anatomy and physiology of pain pathways.

This article provides an integrated review of the basic anatomy and physiology of the pain processing pathways. The transmission and parcellation of noxious stimuli from the peripheral nervous system to the central nervous system is discussed. In addition, the inhibitory and excitatory systems that regulate pain along with the consequences of dysfunction are considered.

Linear measurements of the cerebral ventricles are correlated with adult ventricular volume.

Computation of ventricular volume has important clinical applications but is challenging. We compared linear ventricular measurements to ventricular volume to find a simple to perform quantitative measurement of ventricular size. Linear measurements were correlated with ventricular volumes to different degrees and were reproducible between investigators. Linear measurements provide a quick and simple quantification of ventricular size for use in clinical settings.

Neurological surgery: the influence of physical and mental demands on humans performing complex operations.

Performing neurological surgery is an inherently demanding task on the human body, both physically and mentally. Neurosurgeons routinely perform "high stakes" operations in the setting of mental and physical fatigue. These conditions may be not only the result of demanding operations, but also influential to their outcome. Similar to other performance-based endurance activities, training is paramount to successful outcomes. The inflection point, where training reaches the point of diminishing returns, is intensely debated. For the neurosurgeon, this point must be exploited to the maximum, as patients require both the best-trained and best-performing surgeon. In this review, we explore the delicate balance of training and performance, as well as some routinely used adjuncts to improve human performance.

Beneficial effect of subsequent lesion procedures after nonresponse to initial cingulotomy for severe, treatment-refractory obsessive-compulsive disorder.

BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown. OBJECTIVE: To determine whether a second lesion procedure is beneficial after unsuccessful initial AC. METHODS: In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure. RESULTS: Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04). CONCLUSION: Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy.

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis.

Neurosurgical treatment of Cushing disease.

Cushing disease (CD) is caused by overproduction of adrenocorticotropin by a pituitary adenoma (or, rarely, carcinoma). The diagnosis of CD requires distinguishing it from other hypercortisolemic states with a thorough endocrine workup. CD remains a primarily surgical disease, with remission rates of 70% to 95% following microscopic or endoscopic transsphenoidal surgery.

Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits.

Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks.

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.