The safety and efficacy of onabotulinumtoxinA injections for children and adolescents with chronic migraine: A systematic review and meta-analysis.

OBJECTIVE: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine. BACKGROUND: There are limited evidence-based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence-based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence. METHODS: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta-analyses, and Hedge's g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta-analysis were summarized qualitatively. RESULTS: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta-analyses. After a mean of 2-2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge's g = 0.97, 95% CI 0.58-1.35; p < 0.0001), as did severity (Hedge's g = 1.24, 95% CI 0.55-1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel-group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta-analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred. CONCLUSION: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel-group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo.

Outpatient Approach to Resistant and Refractory Migraine in Children and Adolescents: a Narrative Review.

PURPOSE OF REVIEW: Migraine is one of the top reasons for consulting a pediatric neurologist. Although the majority of children and adolescents who receive evidence-based first-line interventions for migraine will improve substantially, a subset of patients develop resistant or refractory migraine. RECENT FINDINGS: In this review, we summarize the level of evidence for a variety of acute and preventive treatment options to consider in children and adolescents with resistant or refractory migraine. We describe the level of evidence for interventional procedures (onabotulinumtoxinA injections, greater occipital and other nerve blocks), neuromodulation (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, and non-invasive vagal nerve stimulation), calcitonin gene-related peptide (CGRP) pathway antagonists (anti-CGRP monoclonal antibodies and gepants), psychological therapies, and manual therapies (acupuncture, craniosacral therapy, massage and physical therapy, and spinal manipulation).

Peer Coaching to Improve Diabetes Self-Management Among Low-Income Black Veteran Men: A Mixed Methods Assessment of Enrollment and Engagement.

PURPOSE: We undertook a study to ascertain patient characteristics associated with enrollment and engagement in a type 2 diabetes peer health coaching program at an urban health care facility serving predominantly Black veteran men, to improve the targeting of such programs. METHODS: A total of 149 patients declined enrollment in a randomized controlled trial but provided sociodemographic, clinical, and psychosocial information. A total of 290 patients enrolled and were randomized to 2 peer coaching programs; they provided sociodemographic, clinical, and survey data, and were analyzed according to their level of program engagement (167 engaged, 123 did not engage) irrespective of randomization group. Qualitative interviews were conducted with 14 engaged participants. RESULTS: Patients who enrolled were more likely to be Black men, have higher levels of education, have higher baseline hemoglobin A1c levels, describe their diabetes self-management as "fair" or "poor," and agree they "find it easy to get close to others" (P <.05 for each). At the program's end, patients who had engaged were more likely than those who had not to describe their peer coaches as being supportive of their autonomy (mean score, 85.4 vs 70.7; P <.001). The importance of coaches being encouraging, supportive, and having common ground/shared experiences with participants also emerged as key themes in interviews with engaged participants. CONCLUSION: Individuals with greatest perceived need were more likely to enroll in our trial of peer coaching, but the only factor associated with engagement was finding one's coach to support autonomy. Our findings reinforce the importance of training and ensuring fidelity of peer coaches to autonomy-supportive communication styles for participant engagement. In tailoring peer support programs for Black men, future research should elucidate which shared characteristics between participant and peer coach are most important for engagement and improved outcomes.Visual abstract.

The Protective Role of Connectedness on Depression and Suicidal Ideation Among Bully Victimized Youth.

This longitudinal study examined the relationship between connectedness subtypes (family, school, community) and youth depression and suicidal ideation across a 6-month period within a sample of bully victimized youth. Participants were 142 youth (74.6% female, 47.18% African American, 36.62% Caucasian), 12-15 years of age (M = 13.6, SD = 1.12), recruited from an emergency department, who screened positive for elevated levels of bullying victimization and were reevaluated at a 6-month follow-up assessment. Data on bullying victimization, depression, suicidal ideation, and connectedness (family, school, community) were collected at baseline and 6-month follow-up assessments. Separate Bayesian mixed models were used to examine the effects of connectedness (family, school, community) on depression and suicidal ideation while accounting for dependent observations across time points. Prospectively, family and school connectedness were negatively associated with depression and suicidal ideation. Across time points, community connectedness was negatively associated with suicidal ideation. Results highlight the importance of acknowledging and understanding subtypes of interpersonal connectedness among victimized youth as the three subtypes examined (family, school, community) were associated with depression and suicidal ideation. Findings support the importance of bolstering distinct subtypes of connectedness in efforts to improve functioning and attenuate suicide risk among victimized youth.

Clinical Outcomes in Children With Orbital Cellulitis and Radiographic Globe Tenting.

PURPOSE: Axial displacement of the globe with tenting centered on the optic nerve-globe junction is a predictor of visual loss in adults. The purpose of this study was to determine the visual outcomes of children with orbital cellulitis and globe tenting. METHODS: The records of 46 consecutive children with orbital cellulitis at a single tertiary children's hospital were reviewed retrospectively. Initial and final visual acuities were available for 34 of 46 patients (74%). Globe tenting was defined by an angle of 130° or less at the optic nerve-globe junction as derived from sagittal CT or MRI. Visual acuities of 4 children with globe tenting (mean age, 10.3 ± 3.3 years) were compared with those of 30 children without globe tenting (mean age, 10.8 ± 3.5 years). Final logarithm of the minimum angle of resolution visual acuities were analyzed. RESULTS: The mean posterior globe angle was 124.5° ± 8.0° in patients with globe tenting, compared with 145.6° ± 7.4° in the affected eye of the patients without globe tenting (p = 0.002). Final visual acuity was logarithm of the minimum angle of resolution = 0 following treatment in patients with globe tenting and logarithm of the minimum angle of resolution = 0.02 in patients without tenting (p = 0.70). DISCUSSION: We propose that the increased elastic compliance of the optic nerve sheath and sclera in children may contribute to better visual outcomes. CONCLUSIONS: Pediatric orbital cellulitis with globe tenting may not lead to devastating vision loss as previously seen in adults.

Malignant Peripheral Nerve Sheath Tumor of the Lower Eyelid: Case Presentation and Literature Review.

Solitary benign neurogenic tumors are common in the orbit, but only rarely arise from peripheral nerves in the eyelids. In contrast, malignant tumors of neural or nerve sheath elements are exceedingly rare in the orbit and, to date, have never been reported in the lower eyelid. The authors report a 55-year-old man with multiple recurrent lower eyelid masses initially treated as chalazia then misdiagnosed as neurotropic malignant melanoma on pathology. Diagnosis of malignant peripheral nerve sheath tumor was ultimately confirmed histopathologically after surgical resection. The patient has since undergone multiple resections and adjuvant radiotherapy. Twenty-two months since the last procedure, the patient remains disease-free.

Suicide Risk Screening in Healthcare Settings: Identifying Males and Females at Risk.

Suicide is the tenth leading cause of death in the United States, accounting for more than 42,000 deaths in 2014. Although this tragedy cuts across groups defined by age, gender, race/ethnicity, and geographic location, it is striking that nearly four times as many males as females die by suicide in the U.S. We describe the current regulations and recommendations for suicide risk screening in healthcare systems and also describe the aspirational goal of "Zero Suicide," put forth by the National Action Alliance for Suicide Prevention. We then provide information about suicide risk screening tools and steps to take when a patient screens positive for suicide risk. Given the substantially higher suicide rate among males than females, we argue that it is important to consider how we could optimize suicide risk screening strategies to identify males at risk and females at risk. Further research is needed to accomplish this goal. It is recommended that we consider multi-factorial suicide risk screens that incorporate risk factors known to be particularly important for males as well as computerized, adaptive screens that are tailored for the specific risk considerations of the individual patient, male or female. These strategies are not mutually exclusive. Finally, universal suicide risk screening in healthcare settings, especially primary care, specialty medical care, and emergency department settings, is recommended.

Dyadic concordance and other considerations for matching pairs for peer support diabetes prevention interventions: A mixed methods assessment.

OBJECTIVES: Dyadic peer support helps patients make health behavior changes for improved outcomes, yet the impact of matching dyads on demographic characteristics such as race or gender is unknown. Therefore, we investigated associations of concordant characteristics with peer outcomes in a diabetes prevention intervention and qualitatively examined participant perspectives on matching. METHODS: Binary variables for peer-supporter concordance on 6 demographic characteristics were created for 177 peers and 69 supporters. Regression models compared changes in weight, HbA1c, perceived social support, patient activation, and formal diabetes prevention/education program participation for concordant and non-concordant dyads. Semi-structured qualitative interviews were conducted with 39 peers and 34 supporters. RESULTS: Concordance on demographic characteristics was not significantly associated with outcomes. Qualitatively, peers and supporters emphasized that more important than shared demographic characteristics was a supporter's empathic, non-judgmental communication style. CONCLUSIONS: Demographic characteristics for matching supporters with adults with prediabetes are less important than ensuring high-quality coach training in goal setting and communication style, supporting prior research on the necessity of autonomy supportive communication for effective behavioral change interventions. PRACTICE IMPLICATIONS: Existing peer support programs should incorporate fidelity assessments into practice to ensure peer supporter skill in motivational interviewing-based, autonomy supportive communication and brief goal setting.

Optimising tumour coverage and organ at risk sparing for hypofractionated re-irradiation in glioblastoma.

BACKGROUND AND PURPOSE: Re-irradiation may be used for recurrent glioblastoma (GBM) patients. In some cases Planning Target Volume (PTV) under-coverage is necessary to meet organ at risk (OAR) constraints. This study aimed to develop a Volumetric Modulated Arc Therapy planning solution for GBM re-irradiation including a means of assessing if target coverage would be achievable and how much PTV 'cropping' would be required to meet OAR constraints, based on PTV volume and OAR proximity. MATERIALS AND METHODS: For 10 PTVs, 360°, 180°, two coplanar 180° and 180° + non-coplanar 45° arc arrangements were compared using 35 Gy in 10 fractions. Using the preferred arrangement, dose fall-off was modelled to determine the separation required between PTV and OAR to ensure OAR dose constraints were met, with data presented graphically. To evaluate the graph as an aid to planning, seven cases with overlap were replanned in two treatment planning systems (TPSs). RESULTS: There were no significant dosimetric differences between arc arrangements. 180° was preferred due to shorter treatment times. The graph, which indicated if 95% PTV coverage would be achievable based on PTV volume and OAR proximity, was employed in seven cases to guide planning in two TPSs. Plans were deliverable. CONCLUSIONS: Re-irradiation treatment planning can be challenging, especially when PTV under-coverage is necessary. 180° was considered optimal. To assist in the planning process, graphical guidance was produced to inform planners whether PTV under-coverage would be necessary and how much PTV 'cropping' would be required to meet constraints during optimisation.

Coming home: health status and homelessness risk of older pre-release prisoners.

BACKGROUND: Older adults comprise an increasing proportion of the prison and homeless populations. While older age is associated with adverse post-release health events and incarceration is a risk factor for homelessness, the health status and homelessness risk of older pre-release prisoners are unknown. Moreover, most post-release services are geared towards veterans; it is unknown whether the needs of non-veterans differ from those of veterans. OBJECTIVE: To assess health status and risk of homelessness of older pre-release prisoners, and to compare veterans with non-veterans. DESIGN/PARTICIPANTS: Cross-sectional study of 360 prisoners (≥ 55 years of age) within 2 years of release from prison using data from the 2004 Survey of Inmates in State and Federal Correctional Facilities. MAIN MEASURES: Veteran status, health status (based on self-report), and risk of homelessness (homelessness before arrest). KEY RESULTS: Mean age was 61 years; 93.8% were men and 56.5% were white. Nearly 40% were veterans, of whom 77.2% reported likely VA service eligibility. Veterans were more likely to be white and to have obtained a high school diploma or GED. Overall, 79.1% reported a medical condition and 13.6% reported a serious mental illness. There was little difference in health status between veterans and non-veterans. Although 1 in 12 prisoners reported a risk factor for homelessness, the risk factors did not differ according to veteran status. CONCLUSIONS: Older pre-release prisoners had a high burden of medical and mental illness and were at risk for post-release homelessness regardless of veteran status. Reentry programs linking pre-release older prisoners to medical and psychiatric services and to homelessness prevention programs are needed for both veterans and non-veterans.

Smith-Lemli-Opitz syndrome and inborn errors of cholesterol synthesis: summary of the 2007 SLO/RSH Foundation scientific conference sponsored by the National Institutes of Health.

In June 2007, the Smith-Lemli-Opitz/RSH Foundation held a scientific conference hosted jointly by Dr. Robert Steiner from Oregon Health & Science University and Dr. Forbes D. Porter from The Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health. The main goal of this meeting was to promote interaction between scientists with expertise in cholesterol homeostasis, brain cholesterol metabolism, developmental biology, and oxysterol and neurosteroid biochemistry, clinicians researching and treating patients with Smith-Lemli-Opitz syndrome, the patient support organization and families. This report summarizes the presentations and discussions at the conference, represents the conference proceedings, and is intended to foster collaborative research and ultimately improve understanding and treatment of Smith-Lemli-Opitz syndrome and other inborn errors of cholesterol synthesis.

IPEM topical report: the first UK survey of dose indices from radiotherapy treatment planning computed tomography scans for adult patients.

CT scans are an integral component of modern radiotherapy treatments, enabling the accurate localisation of the treatment target and organs-at-risk, and providing the tissue density information required for the calculation of dose in the treatment planning system. For these reasons, it is important to ensure exposures are optimised to give the required clinical image quality with doses that are as low as reasonably achievable. However, there is little guidance in the literature on dose levels in radiotherapy CT imaging either within the UK or internationally. This IPEM topical report presents the results of the first UK wide survey of dose indices in radiotherapy CT planning scans. Patient dose indices were collected for prostate, gynaecological, breast, lung 3D, lung 4D, brain and head and neck scans. Median values per scanner and examination type were calculated and national dose reference levels and 'achievable levels' of CT dose index (CTDIvol), dose-length-product (DLP) and scan length are proposed based on the third quartile and median values of these distributions, respectively. A total of 68 radiotherapy CT scanners were included in this audit. The proposed dose reference levels for CTDIvol and DLP are; prostate 16 mGy and 570 mGy · cm, gynaecological 16 mGy and 610 mGy · cm, breast 10 mGy and 390 mGy · cm, lung 3D 14 mGy and 550 mGy · cm, lung 4D 63 mGy and 1750 mGy · cm, brain 50 mGy and 1500 mGy · cm and head and neck 49 mGy and 2150 mGy · cm. Significant variations in dose indices were noted, with head and neck and lung 4D yielding a factor of eighteen difference between the lowest and highest dose scanners. There was also evidence of some clustering in the data by scanner manufacturer, which may be indicative of a lack of local optimisation of individual systems to the clinical task. It is anticipated that providing this data to the UK and wider radiotherapy community will aid the optimisation of treatment planning CT scan protocols.

A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans.

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.

Dura splitting decompression for Chiari I malformation in pediatric patients: clinical outcomes, healthcare costs, and resource utilization.

BACKGROUND: Dural splitting decompression may be an effective and safe treatment for Chiari I malformation. OBJECTIVE: To compare clinical outcomes, complications, and resource utilization for patients undergoing Chiari I decompression with or without duraplasty. METHODS: Between 2000 and 2009, the senior author performed 113 Chiari I decompression operations with dural splitting or duraplasty in children less than 18 years of age; 110 were included in a retrospective cohort analysis of safety, efficacy, and treatment cost. Patients without significant syringomyelia underwent dural splitting decompression, and patients with syringomyelia underwent duraplasty. RESULTS: : Sixty-three patients without significant syringomyelia (57%) underwent dural splitting decompression. They were significantly younger than patients undergoing duraplasty (8.3 ± 4.9 years vs 10.4 ± 4.4 years; P < .05). Headaches improved or resolved in most patients in both groups (90.5% vs 93.6%; P = .59). Dysphagia, long tract signs, cranial nerve, and bulbar symptoms also improved similarly in both groups. Three duraplasty patients were treated medically for aseptic meningitis; one underwent reoperation for a symptomatic pseudomeningocele. No patient undergoing dural splitting decompression experienced a cerebrospinal fluid-related complication. Extradural decompression required less operative time than duraplasty (105.5 vs 168.9 minutes, P < .001), a shorter length of stay (2.4 vs 2.8 days, P = .011), and lower total cost for the primary hospitalization ($26 837 vs $29 862, P = .015). CONCLUSION: In this retrospective cohort study, dural splitting decompression was equally effective, safer, and lower cost for treatment of Chiari I malformation without syringomyelia. A multicenter trial with groups balanced for the presence of syringomyelia is necessary to determine whether these results are generalizable.

The evaluation of a deformable image registration segmentation technique for semi-automating internal target volume (ITV) production from 4DCT images of lung stereotactic body radiotherapy (SBRT) patients.

PURPOSE: To evaluate a deformable image registration (DIR) segmentation technique for semi-automating ITV production from 4DCT for lung patients, in terms of accuracy and efficiency. METHODS: Twenty-five stereotactic body radiotherapy lung patients were selected in this retrospective study. ITVs were manually delineated by an oncologist and semi-automatically produced by propagating the GTV manually delineated on the mid-ventilation phase to all other phases using two different DIR algorithms, using commercial software. The two ITVs produced by DIR were compared to the manually delineated ITV using the dice similarity coefficient (DSC), mean distance between agreement and normalised DSC. DIR-produced ITVs were assessed for their clinical suitability and also the time savings were estimated. RESULTS: Eighteen out of 25 ITVs had normalised DSC>1 indicating an agreement with the manually produced ITV within 1mm uncertainty. Four of the other seven ITVs were deemed clinically acceptable and three would require a small amount of editing. In general, ITVs produced by DIR were smoother than those produced by manual delineation. It was estimated that using this technique would save clinicians on average 28 min/patient. CONCLUSIONS: ABAS was found to be a useful tool in the production of ITVs for lung patients. The ITVs produced are either immediately clinically acceptable or require minimal editing. This approach represents a significant time saving for clinicians.

Risk factors for all-cause, overdose and early deaths after release from prison in Washington state.

BACKGROUND: High mortality rates after release from prison have been well-documented, particularly from overdose. However, little is known about the risk factors for death after release from prison. Therefore, the objective of this study was to determine the demographic and incarceration-related risk factors for all-cause, overdose and early mortality after release from prison. METHODS: We conducted a retrospective cohort study of inmates released from a state prison system from 1999 through 2003. The cohort included 30,237 who had a total of 38,809 releases from prison. Potential risk factors included gender, race/ethnicity, age, length of incarceration, and community supervision. Cox proportional hazards regression was used to determine risk factors for all-cause, overdose and early (within 30 days of release) death after release from prison. RESULTS: Age over 50 was associated with an increased risk for all-cause mortality (hazard ratio [HR] 2.67 for each decade increase, 95% confidence interval [CI] 2.23, 3.20) but not for overdose deaths or early deaths. Latinos were at decreased risk of death compared to Whites only for all-cause mortality (HR 0.61, 95% CI 0.42, 0.87). Increasing years of incarceration were associated with a decreased risk of all-cause mortality (HR 0.95, 95% CI 0.91, 0.99) and overdose deaths (HR 0.80, 95% CI 0.68, 0.95), but not early deaths. Gender and type of release were not significantly associated with all-cause, overdose or early deaths. CONCLUSIONS: Age, ethnicity and length of incarceration were associated with mortality after release from prison. Interventions to reduce mortality among former inmates are needed.

Visual signals of status and rival assessment in Polistes dominulus paper wasps.

Aggressive competition is an important aspect of social interactions, but conflict can be costly. Some animals are thought to minimize the costs of conflict by using conventional signals of agonistic ability (i.e. badges of status) to assess rivals. Although putative badges have been found in a range of taxa, little research has tested whether individuals use badges to assess potential rivals before they engage in aggressive contests. Here, choice trials were used to test how the variable black facial patterns in Polistes dominulus wasps are used during rival assessment. Focal wasps were given access to two patches of food, each guarded by a wasp whose facial pattern had been experimentally altered. Wasps chose food patches based on the facial pattern of the guard, preferring to challenge guards with facial patterns indicating a low level of quality, while avoiding guards with facial patterns indicating a high level of quality. Therefore, status badges play an important role during rival assessment; paper wasps use facial patterns alone to quickly assess the agonistic abilities of strangers.

Does patient-provider racial/ethnic concordance influence ratings of trust in people with HIV infection?

Despite widely available and effective treatments, there are racial/ethnic disparities in HIV-related mortality rates. The reason for inadequate HIV/AIDS management among minority populations is not fully understood, however recent research indicates that patients rate the quality of their health care higher if they are racially/ethnically concordant with their providers. As trust plays prominently on health care ratings, we examined whether racial/ethnicity concordance was associated with two dimensions of trust, trust in the provider and mistrust in the health care system, in 380 HIV infected people New York City. In this sample, concordance was associated with lower mistrust in the health care system, but not with trust in provider. We conclude that in this patient population and within the health care system available to them, racial/ethnic concordance might be more important for helping patients to understand and navigate the health care system rather than in interpersonal relationships with a single provider.