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OBJECTIVES: To characterize the short-term prognosis of a clinical population of pediatric and young adult patients with migraine and explore predictors of clinical worsening while in care. METHODS: This was a retrospective study of all migraine patients seen at the Cincinnati Children’s Hospital Headache Center from 09/01/2006 to 12/31/2017, who had at least one follow-up visit within 1–3 months of the index visit analyzed. Included data were: age, sex, race, primary ICHD diagnosis, chronic migraine, medication overuse, history of status migrainosus, BMI percentile, headache frequency, headache severity, PedMIDAS score, allodynia, preventive treatment type, lifestyle habits, disease duration, depressive and anxiety symptoms. Clinical worsening was defined as an increase of 4 or more headache days per month between the index visit and the follow-up visit. RESULTS: Data for 13,160 visit pairs (index and follow-up), from 5,316 patients were analyzed. Clinical worsening occurred in only 14.5% (1,908/13,160), whereas a reduction in headache frequency was observed in 56.8% of visit intervals (7,475/13,160), with 34.8% of the intervals (4,580/13,160) showing a reduction of 50% or greater. The change in headache frequency was minimal (increase in 0–3 headaches/month) in 28.7% of intervals (3,737/13,160). In the multivariable model, the odds of worsening were significantly higher with increasing age, female sex, chronic migraine, status migrainosus, depressive symptoms, higher PedMIDAS scores, and use of nutraceuticals, whereas the odds of worsening were lower for summer visits, caffeine drinkers, higher headache frequencies and use of pharmaceuticals. CONCLUSIONS: The majority of pediatric patients who receive multimodal interdisciplinary care for migraine improve over time. Our findings highlight a set of clinical features that may help in identifying specific factors that may contribute to an unfavorable short-term prognosis.

The current review presents findings from investigations of migraine in children. The presentation of pediatric migraine, related consequences, and medication treatments are reviewed.A number of advancements have been made in the study of the presentation, disability, and treatments for migraine in children. However, recent research suggests that not all approaches are equally effective in the treatment of migraine in children. Specifically, a recent study comparing pharmacological interventions found that preventive medications were not statistically more effective than placebo in children. Consistent findings showing clinically meaningful placebo response rates, shorter duration of headaches and other characteristic features (e.g. frontal, bilateral location) have been barriers to the design of randomized clinical trials in children and adolescents with migraine. Better understanding of treatment mechanisms for medication interventions is needed.Several migraine treatments have determined to be effective for use in children but few controlled studies have evaluated the effectiveness of medication treatments. Recent research suggests that preventive medications may not be more effective than placebo. Additional research is needed to evaluate the effectiveness of medication treatment in migraine headache care.

BACKGROUND: Studies suggest that migraine is often underdiagnosed and inadequately treated in the primary care setting, despite many patients relying on their primary care provider (PCP) to manage their migraine. Many women consider their women’s healthcare provider to be their PCP, yet very little is known about migraine knowledge and practice patterns in the women’s healthcare setting. OBJECTIVE: The objective of this study was to assess women’s healthcare providers’ knowledge and needs regarding migraine diagnosis and treatment. METHODS: The comprehensive survey assessing migraine knowledge originally developed for PCPs was used in this study, with the addition of a section regarding the use of hormonal medications in patients impacted by migraine. Surveys were distributed online, and primarily descriptive analyses were performed. RESULTS: The online survey was completed by 115 women’s healthcare providers (response rate 28.6%; 115/402), who estimated that they serve as PCPs for approximately one-third of their patients. Results suggest that women’s healthcare providers generally recognize the prevalence of migraine, but experience some knowledge gaps regarding migraine management. Despite 82.6% (95/115) of survey respondents feeling very comfortable or somewhat comfortable with diagnosing migraine, only 57.9% (66/114) reported routinely asking patients about headaches during annual visits. Very few were familiar with the American Academy of Neurology guidelines on preventative treatment (6.3%; 7/111) and the Choosing Wisely Campaign recommendations on migraine treatment (17.3%; 19/110), and many prescribed medications known to contribute to medication overuse headache. In addition, only 24.3% (28/115) would order imaging for a new type of headache, 35.7% (41/115) for worsening headache, and 47.8% (55/115) for headache with neurologic symptoms; respondents cited greater tendency with sending patients to an emergency department for the same symptoms. Respondents had limited knowledge of evidence-based, non-pharmacological treatments for migraine (i.e., biofeedback or cognitive behavioral therapy), with nearly none placing referrals for these services. Most providers were comfortable prescribing hormonal contraception (mainly progesterone only) to women with migraine without aura (80.9%; 89/110) and with aura (72.5%; 79/109), and followed American College of Obstetricians and Gynecologists (ACOG) guidelines to limit combination hormonal contraception for patients with aura. When queried, 6.3% or less (5/79) of providers would prescribe estrogen-containing contraception for women with migraine with aura. Only 37.3% (41/110) of respondents reported having headache/migraine education. Providers indicated interest in education pertaining to migraine prevention and treatment (96.3%; 105/109), migraine-associated disability (74.3%; 81/109), and diagnostic testing (59.6%; 65/109). CONCLUSION: Women’s healthcare providers appear to have several knowledge gaps regarding the management of migraine in their patients. These providers would likely benefit from access to a headache-specific educational curriculum to improve provider performance and patient outcomes.

This study proposes a prosthetic hand with a simple control algorithm and off-the-shelf electronics. We designed this hand to be used and repaired in underdeveloped regions. A differential sEMG signal is obtained from the flexor digitorum superficialis and extensor digitorum muscles to control the position of the hand’s grasp. Three different hand control schemes (visual, vibrotactile and visual plus vibrotactile) were compared and tested in ten able-bodied individuals. We observed a better performance of the visual and vibrotactile control overall, but the vibrotactile feedback increased performance after several interactions. In subjective data evaluations vibrotactile and visual feedback had the highest scores in light and medium pressures, while visual-only feedback type had the highest average score for hard pressure.

To characterize the clinical features of a large sample of children, adolescents, and young adults with a history of status migrainosus (SM) and to describe their short-term prognosis.Data on the clinical characteristics of children and adolescents with SM are sparse and little is known about the prognosis of this population.This was a retrospective clinical cohort study that included patients from the Cincinnati Children's Headache Center if they had a diagnosis of migraine and data available for a 1-3 months follow-up interval. Data extracted from the initial interval visit (visit A) included: age, sex, race, migraine diagnosis, SM history, chronic migraine, medication overuse headache (MOH), body mass index (BMI), headache frequency, headache severity, disability, allodynia and lifestyle habits: caffeine intake, meal skipping, sleep duration, exercise frequency, and fluid intake. Data extracted from the initial consultation visit included: months with headache at initial consultation visit, patient endorsing "feeling depressed" and anxiety symptoms. Headache frequency and visit type were also measured at the second visit (visit B) in the follow-up interval. A multivariate logistic regression model with a backward elimination procedure was created to model the odds of having a diagnosis of SM using the cross-sectional predictor variables above. Second, chi-square tests were used to compare the proportion of patients with SM to the proportion of patients without SM who had each of the following outcomes in the short-term follow-up window: treatment response (50% or greater reduction in headache frequency), overall reduction in headache frequency (reduction of 1 or more headache days/month), minimal change in headache frequency (increase in 0-3 headache days/month), and clinical worsening (increase in 4 or more headache days/month).A total of 5316 youth with migraine were included and 559 (10.5%) had a history of SM. In the multivariate logistic regression model, predictors significantly associated with SM were: older age (OR = 1.13, 95% CI = 1.09-1.17, P .0001), migraine with aura (MWA) (OR = 1.30, 95% CI = 1.03-1.65, P = .03), MOH (OR = 1.72, 95% CI = 1.30-2.28, P = .0001), headache frequency (OR = 0.99, 95% CI = 0.97-0.99, P = .030), higher headache severity (OR = 1.08, 95% CI = 1.02-1.15, P = .009), months with headache at initial consultation (OR = 1.00, 95% CI = 1.00-1.01, P = .042), and admission to infusion center at visit B (OR = 2.27, 95% CI = 1.38-3.72, P = .001). Patients with a history of SM were more likely to experience an increase in 4 or more headache days per month at follow-up: 15.2% as compared to 11.1% of those without SM, χYouth with SM represent a distinct subgroup of the migraine population and have an unfavorable short-term prognosis.

OBJECTIVES To characterize a population of pediatric patients visiting an infusion center for acute migraine and determine predictors of first-line treatment success in this population. BACKGROUND Though migraine is common in the pediatric emergency department and specialized infusion centers, little is known about this patient population and whether or not clinical data can be used to predict treatment response. METHODS This was an observational study involving a retrospective analysis of data from visits to the Cincinnati Children's Hospital infusion center for treatment of an acute migraine. Data were extracted from a database and chart reviews were completed for missing or outlying data. Descriptive statistics were used to outline patient: sex, age, race, primary ICHD-III diagnosis, chronic migraine, medication overuse headache (MOH), headache frequency, month of treatment, headache severity, headache duration, use of acute medication at home in the past 24 hours and treatment received (metoclopramide vs prochlorperazine and dexamethasone vs no dexamethasone). The odds of success of first-line intervention were modeled using simple logistic regression with the above characteristics used as predictors. Predictors with a P value

Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery. An elastic net algorithm applied to the high-dimensional mass cytometry dataset identified a cross-validated model consisting of 20 interrelated immune features that separated patients assigned to AES from controls. The model revealed wide-ranging effects of AES on innate and adaptive immune compartments. Notably, AES increased STAT1 and STAT3 signaling responses in lymphoid cell subsets after surgery, consistent with enhanced adaptive mechanisms that may protect against postsurgical infection. Unexpectedly, AES also increased ERK and P38 MAPK signaling responses in monocytic myeloid-derived suppressor cells, which was paired with their pronounced expansion. These results provide novel mechanistic arguments as to why AES may exert context-specific beneficial or adverse effects in patients with critical illness. This study lays out an analytical framework to distill high-dimensional datasets gathered in an interventional clinical trial into a fairly simple model that converges with known biology and provides insight into novel and clinically relevant cellular mechanisms.

We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10–17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits. Data from daily headache diaries are presented for each day and according to 28-day periods. Trajectories of improvement indicate initial decrease in headache days began during the first month of treatment, for both groups, and continued to decrease throughout treatment. The CBT+A group had greater daily improvement than the HE+A group. A significantly greater proportion of the CBT+A group had a ≥50% reduction in headache days each month, and a significantly greater proportion of the CBT+A group had ≤4 headache days per month in months 3 through 5. Results indicate the trajectory of decrease in headache days is significantly better for patients receiving CBT+A versus HE+A. Perspective This article presents daily information about headache frequency over a 20-week clinical trial. Youth with chronic migraine who received CBT+A improved faster than those in the control group. Findings provide clinicians with evidence-based expectations for treatment response over time and ways of monitoring treatment success. Trial registration clinicaltrials.gov identifier NCT00389038 .

Summary Background The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. Methods 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. Findings We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52–66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort. Interpretation Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Funding Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

BackgroundThe last two decades have seen substantial expansion of childhood vaccination programmes in low and middle income countries (LMICs). Here we quantify the health impact of these programmes by estimating the deaths and disability-adjusted life years (DALYs) averted by vaccination with ten antigens in 98 LMICs between 2000 and 2030.MethodsIndependent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B (HepB), Haemophilus influenzae type b (Hib), human papillomavirus (HPV), Japanese encephalitis (JE), measles, Neisseria meningitidis serogroup A (MenA), Streptococcus pneumoniae, rotavirus, rubella, yellow fever. Using standardized demographic data and vaccine coverage estimates for routine and supplementary immunization activities, the impact of vaccination programmes on deaths and DALYs was determined by comparing model estimates from the no vaccination counterfactual scenario with those from a default coverage scenario. We present results in two forms: deaths/DALYs averted in a particular calendar year, and in a particular annual birth cohort.FindingsWe estimate that vaccination will have averted 69 (2.5-97.5% quantile range 52-88) million deaths between 2000 and 2030 across the 98 countries and ten pathogens considered, 35 (29-45) million of these between 2000-2018. From 2000-2018, this represents a 44% (36-57%) reduction in deaths due to the ten pathogens relative to the no vaccination counterfactual. Most (96% (93-97%)) of this impact is in under-five age mortality, notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 122 (96-147) million deaths will be averted by vaccination, of which 58 (39-75) and 38 (26-52) million are due to measles and Hepatitis B vaccination, respectively. We estimate that recent increases in vaccine coverage and introductions of additional vaccines will result in a 72% (61-79%) reduction in lifetime mortality caused by these 10 pathogens in the 2018 birth cohort.InterpretationIncreases in vaccine coverage and the introduction of new vaccines into LMICs over the last two decades have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained.

Background: The last two decades have seen substantial expansion of childhood vaccination programmes in low and middle income countries (LMICs). Here we quantify the health impact of these programmes by estimating the deaths and disability-adjusted life years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. Methods: Independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B (HepB), Haemophilus influenzae type b (Hib), human papillomavirus (HPV), Japanese encephalitis (JE), measles, Neisseria meningitidis serogroup A (MenA), Streptococcus pneumoniae, rotavirus, rubella, yellow fever. Using standardized demographic data and vaccine coverage estimates for routine and supplementary immunization activities, the impact of vaccination programmes on deaths and DALYs was determined by comparing model estimates from the no vaccination counterfactual scenario with those from a default coverage scenario. We present results in two forms: deaths/DALYs averted in a particular calendar year, and in a particular annual birth cohort. Findings: We estimate that vaccination will have averted 69 (2⋅5-97⋅5% quantile range 52-88) million deaths between 2000 and 2030 across the 98 countries and ten pathogens considered, 35 (29-45) million of these between 2000-2018. From 2000-2018, this represents a 44% (36-57%) reduction in deaths due to the ten pathogens relative to the no vaccination counterfactual. Most (96% (93-97%)) of this impact is in under-five age mortality, notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 122 (96-147) million deaths will be averted by vaccination, of which 58 (39-75) and 38 (26-52) million are due to measles and Hepatitis B vaccination, respectively. We estimate that recent increases in vaccine coverage and introductions of additional vaccines will result in a 72% (61-79%) reduction in lifetime mortality caused by these 10 pathogens in the 2018 birth cohort. Interpretation: Increases in vaccine coverage and the introduction of new vaccines into LMICs over the last two decades have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Funding Statement: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill & Melinda Gates Foundation (BMGF). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMCfunded institutions represented in this paper: Imperial College London, London School of Hygiene & Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Metiers). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: Professor Hallett, Professor Grassly, Dr Cucunuba, Professor Jit, Dr Xiang Li, Dr Mukandavire, Ms Woodruff, Professor Ferguson, Dr Garske); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). In addition, the following funding declarations are noted: Dr Eilertson and Dr Ferrari report grants from BMGF, outside the submitted work. Mr Gamkrelidze, Dr Razavi and Mr Razavi-Shearer report grants from John C Martin Foundation during the conduct of the study; and grants from AbbVie, Gilead, Intercept, Pan American Health Organization, and Association of State and Territorial Health Officials outside the submitted work; all three authors are employees of the Center for Disease Analysis Foundation which had no role in study design, data collection and analysis, interpretation of data, or preparation of the manuscript. Dr Gaythorpe reports personal fees from Wellcome Genome Campus advanced courses and scientific conferences, and grants from MRC during the conduct of the study. Dr Hallett reports grants and personal fees from WHO, Pharos, Avenhir Health, outside the submitted work. Dr Nayagam reports Consultancy work for WHO and Pharos Global Health Advisors, and acknowledges support from NIHR Imperial Biomedical Research Centre (BRC). Dr Trotter reports personal fees from GSK, outside the submitted work. Professor Hallett, Dr Nayagam, Dr Garske, Dr Gaythorpe, Dr Hinsley, Dr Jean, and Professor Ferguson acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development (MR/R015600/1). Development of LSHTM's models for HPV, measles, PCV, Hib and rotavirus was funded by WHO, Gavi and BMGF under several grants, past and current. BMGF supported the development and maintenance of the Lives Saved Tool. Dr Resch and Mr Sy acknowledge other funding from BMGF not related to this work and with no influence on the manuscript or the decision to submit it for publication. Declaration of Interests: This publication is authored by members of the Vaccine Impact Modelling Consortium (VIMC, www.vaccineimpact.org). VIMC is jointly funded by Gavi, the Vaccine Alliance, and by the Bill & Melinda Gates Foundation. The views expressed are those of the authors and not necessarily those of the Consortium or its funders. The funders were given the opportunity to review this paper prior to publication, but the final decision on the content of the publication was taken by the authors. Consortium members received funding from Gavi and BMGF via VIMC during the course of the study (see funding statement above). In addition, the following potential conflicts of interest were disclosed: Dr Eilertson and Dr Ferrari report grants from Bill and Melinda Gates Foundation, outside the submitted work. Dr Gamkrelidze, Dr Razavi and Dr Razavi-Shearer report grants from John C Martin Foundation during the conduct of the study; and grants from AbbVie, Gilead, Intercept, Pan American Health Organization, and Association of State and Territorial Health Officials outside the submitted work. Dr Gaythorpe reports personal fees from Wellcome Genome Campus advanced courses and scientific conferences, and grants from MRC during the conduct of the study. Dr Hallett reports grants and personal fees from WHO, Pharos, Avenhir Health, outside the submitted work. Dr Nayagam reports Consultancy work for WHO and Pharos Global Health Advisors. Dr Trotter reports personal fees from GSK, outside the submitted work. Professor Ferguson reports grants from UK Medical Research Council during the conduct of the study, and grants from NIH NIGMS, UK National Institute of Health Research, Janssen Pharmaceuticals, outside the submitted work. Dr Garske reports grants from Janssen Pharmaceuticals, outside the submitted work. Ethical Approval Statement: Not required.

Objective The purpose of this investigation was to examine treatment adherence to medication and lifestyle recommendations among pediatric migraine patients using electronic monitoring systems. Background Nonadherence to medical treatment is a significant public health concern, and can result in poorer treatment outcomes, decreased cost-effectiveness of medical care, and increased morbidity. No studies have systematically examined adherence to medication and lifestyle recommendations in adolescents with migraine outside of a clinical trial. Methods Participants included 56 adolescents ages 11-17 who were presenting for clinical care. All were diagnosed with migraine with or without aura or chronic migraine and had at least 4 headache days per month. Medication adherence was objectively measured using electronic monitoring systems (Medication Event Monitoring Systems technology) and daily, prospective self-report via personal electronic devices. Adherence to lifestyle recommendations of regular exercise, eating, and fluid intake were also assessed using daily self-report on personal electronic devices. Results Electronic monitoring indicates that adolescents adhere to their medication 75% of the time, which was significantly higher than self-reported rates of medication adherence (64%). Use of electronic monitoring of medication detected rates of adherence that were significantly higher for participants taking once daily medication (85%) versus participants taking twice daily medication (59%). Average reported adherence to lifestyle recommendations of consistent noncaffeinated fluid intake (M = 5 cups per day) was below recommended levels of a minimum of 8 cups per day. Participants on average also reported skipping 1 meal per week despite recommendations of consistently eating three meals per day. Conclusions Results suggest that intervention focused on adherence to preventive treatments (such as medication) and lifestyle recommendations may provide more optimal outcomes for children and adolescents with migraine and their families. Once daily dosing of medication may be preferred to twice daily medication for increased medication adherence among children and adolescents.

Non-pharmacological options for the management of chronic daily headache are of increasing interest to patients and providers given the high cost of prescription medication, poor efficacy, and concern for potential side effects. Options include behavioral approaches, relaxation techniques, and lifestyle modification, which can be used alone or in conjunction with traditional pharmaceutical therapies. The goals of a behavioral approach are to increase functioning and minimize disability related to chronic pain and should be taught or administered by a trained professional. Lifestyle modification involves educating the patient about the importance of maintaining a healthy balanced diet rich in vegetables, without skipping meals, staying hydrated, practicing good sleep hygiene, incorporating regular exercise, and avoiding caffeine and other potential triggers. This chapter focuses on the evidence that supports current practice recommendations for managing chronic daily headache and highlights limitations where further research is warranted.

Migraine is prevalent in children and adolescents and constitutes an important cause of disability in this population. Early, effective treatment of paediatric migraine is likely to result in improved outcomes. Findings from the past few years suggest that a biopsychosocial approach that uses interdisciplinary multimodal care is most effective for treatment of migraine in the paediatric population. Key elements of this management include effective and timely acute pharmacological interventions (such as NSAIDs and/or triptans), education of patients regarding self-management techniques, and psychological interventions such as biofeedback, relaxation and cognitive-behavioural therapy. The efficacy of current pharmacological or nutraceutical interventions for migraine prevention in children and adolescents is unclear, although reported placebo response patterns suggest that the effect of pill-taking behaviour is positive. As such, clinicians can consider adding a preventive intervention that involves a daily pill-taking behaviour to evidence-based non-pharmacological first-line preventive interventions (such as cognitive-behavioural therapy). More rigorous research is needed to delineate the role of pharmacological and nutraceutical interventions, the mechanisms of the clinically relevant placebo response, and interventions that enhance this response for migraine prevention in this population. Given the prevalence of migraine, cost-effective and efficacious strategies are needed for the large-scale delivery of interdisciplinary multimodal paediatric migraine care.

Migraine is a common condition that for many begins in childhood and may progress over the course of one's life. The transition from adolescence to adulthood is a critical time for those who suffer from migraine and can be marked by a variety of important considerations for the patient and practitioner. Medication choices may be a challenge during adolescent years as Food and Drug Administration (FDA) approved options are few and many more studies are needed to understand the benefits and risks of use of these agents in adolescents. However, as patients transition to adulthood, FDA approved options and the level of evidence improve significantly. Late adolescents may also struggle with a variety of psychiatric comorbidities that may simultaneously create challenges in determining treatment but also open opportunities to manage multiple comorbidities and address underlying depression, anxiety, and behavioral issues. For late adolescent girls, the beginning of sexual activity, onset of gynecologic conditions, or presence of irregular or painful menses may raise questions regarding the use of oral contraceptives (OCs). Given data on the risks of these medications in women with migraine, especially those with aura or those who smoke, important conversations between physicians and their migraine patients can help risk stratify and determine the risk/benefit profile for the potential use of these agents. Much more data are needed to fully understand the transition from adolescence to adulthood for those suffering with migraine and this article seeks to shed light on the limited understanding currently available in established literature.

OBJECTIVE To review the challenges and potential solutions in treatment options for quality migraine care in adult patients who are under or uninsured. BACKGROUND The Affordable Care Act has improved access to health care for many; however, those who are underserved continue to face treatment disparities and have inadequate access to appropriate migraine management. METHODS This manuscript is the second of a 2-part narrative review which was performed after a series of discussions within the Underserved Populations in Headache Medicine Special Interest Section meetings of the American Headache Society. Literature was reviewed for key concepts underpinning conceptual boundaries and a broad overview of the subject matter. Published guidelines, state-specific Medicaid websites, headache quality measurement sets, literature review, and expert opinion were used to tailor suggested treatment options and therapeutic strategies. In this second part of our narrative review, we explored migraine care strategies and considerations for underserved and vulnerable adult populations with migraine. RESULTS Although common, migraine remains untreated, particularly among those of low socioeconomic status. Low socioeconomic status may play an important role in the disease progression, prescription of hazardous medications such as opioids, outcomes, and quality of life of patients with migraine and other headache disorders. There are some evidence-based and guideline supported treatment options available at low cost that include prescription medications and supplements, though approved devices are costly. Resources available online and simple nonpharmacological strategies may be particularly useful in the underserved migraine population. CONCLUSIONS We identified and discussed migraine treatment barriers that affect underserved populations in the US and summarized practical, cost-effective strategies to surmount them. However, more research is needed to identify the best cost-effective measures for migraine management in underserved and vulnerable patients who are uninsured or underinsured.

Objective To review the scope of the problem facing individuals with migraine who are under- or uninsured. In this first of a 2-part narrative review, we will explore migraine epidemiology and the challenges that face this vulnerable population. Background Implementation of the Affordable Care Act has improved access to health care for many individuals who were previously uninsured, but there are many, particularly those of certain demographics, who are at high risk for worse outcomes. Methods A narrative review was performed after a series of discussions within the Underserved Populations in Headache Medicine Special Interest Section meetings of the American Headache Society. Literature was reviewed for key concepts underpinning conceptual boundaries and a broad overview of the subject matter. Published guidelines, state-specific Medicaid websites, headache quality measurement set, literature review, and expert opinion were used to tailor suggested treatment options and therapeutic strategies. Results Migraine is common, yet remains underdiagnosed and associated with worse outcomes among those of under-represented backgrounds and those who are underinsured or uninsured. Low socioeconomics may play an important role in the disease progression, characteristics, outcome, and quality of life of patients with migraine and other headache disorders. Other barriers to optimal care include time constraints, lack of access to specialty providers, transportation, and financial limitations. Conclusion There are many barriers and challenges that affect people with migraine who are underinsured or uninsured, particularly those of under-represented racial backgrounds and of lower socioeconomic status.

Background and Objectives Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. Methods A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. Results The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P

BackgroundFifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty.AimsTo determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine.MethodsThis was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates.ResultsModels of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p ConclusionAge and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under ‘real world’ conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. publishedVersion

Objectives To examine treatment adherence among children and adolescents with chronic migraine who volunteered to be in a clinical trial using 3 measures: treatment session attendance, therapy homework completion, and preventive medication use by daily diary. Materials and methods Analyses are secondary from a trial of 135 youth aged 10 to 17 years diagnosed with chronic migraine and with a Pediatric Migraine Disability Score over 20. Participants were randomly assigned to cognitive-behavioral therapy plus amitriptyline (CBT+A, N=64) or headache education plus amitriptyline (HE+A, N=71). Therapists recorded session attendance. Completion of homework/practice between sessions was reported to therapists by patients. Patients reported preventive medication adherence using a daily headache diary. Results Mean session attendance adherence out of 10 treatment sessions was 95% for CBT+A and 99% for HE+A. CBT+A participants reported completing a mean of 90% of home practice of CBT skills between the 10 sessions. Participants reported taking amitriptyline daily at a mean level of 90% when missing diaries were excluded and 79% when missing diaries were considered as missed doses of medication. Discussion Our findings demonstrate that youth with chronic migraine who agree to be a part of a clinical trial do quite well at attending therapy sessions, and report that they are adherent to completing home/practice between sessions and taking medication. These results lend further support to consideration of CBT+A as a first-line treatment for youth with chronic migraine and suggest that measurement of adherence when this treatment is provided in practice will be important.

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a ‘real world’ context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. publishedVersion

Background: Environmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI). Methods: Participants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996–1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models. Results: The highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI

Background : An estimated 23 million infants are still not being benefitted from routine immunization services. We assessed how many children failed to be fully immunized even though they or their mothers were in contact with health services to receive other interventions. Design : Fourteen countries with Demographic and Health Surveys and Multiple Indicator Cluster Surveys carried out after 2000 and with coverage for DPT (Diphtheria-tetanus-pertussis) vaccine below 70% were selected. We defined full immunization coverage (FIC) as having received one dose of BCG (bacille Calmette-Guerin), one dose of measles, three doses of polio, and three doses of DPT vaccines. We tabulated FIC against: antenatal care (ANC), skilled birth attendance (SBA), postnatal care for the mother (PNC), vitamin A supplementation (VitA) for the child, and sleeping under an insecticide-treated bed-net (ITN). Missed opportunities were defined as the percentage of children who failed to be fully immunized among those receiving one or more other interventions. Results : Children who received other health interventions were also more likely to be fully immunized. In nearly all countries, FIC was lowest among children born to mothers who failed to attend ANC, and highest when the mother had four or more ANC visits Cote d’Ivoire presented the largest difference in FIC: 54 percentage points (pp) between having four or more ANC visits and lack of ANC. SBA was also related with higher FIC. For instance, the coverage in children without SBA was 36 pp lower than for those with SBA in Nigeria. The largest absolute difference on FIC in relation to PNC was observed for Ethiopia: 31 pp between those without and with PNC. FIC was also positively related with having received VitA. The largest absolute difference was observed in DR Congo: 41 pp. The differences in FIC among whether or not children slept under ITN were much smaller than for other interventions. Haiti presented the largest absolute difference: 16 pp. Conclusions : Our results show the need to develop and implement strategies to vaccinate all children who contact health services in order to receive other interventions. Keywords: vaccines; vaccination; immunization; child health; health services (Published: 3 May 2016) Citation: Glob Health Action 2016, 9 : 30963 - http://dx.doi.org/10.3402/gha.v9.30963 Supplementary files: To access the supplementary material for this article, please see Supplementary files under ‘Article Tools’

The diagnosis and management of migraine headaches can be challenging in children and adolescents. The description of migraine in this population may include symptoms that are not typically described in adults. Treatment options for pediatric migraine is increasing, however remain limited. This article will go through the key components to diagnosing migraine in pediatric patients as well as give options for short and long-term management.

The recognition of the diagnosis of migraine in children is increasing. Early and aggressive treatment of migraine in this population with the use of over-the-counter medications has proven effective. The off-label use of many migraine-specific medications is often accepted in the absence of sufficient evidenced-based trials. Mild to severe cases of migraine should be treated with nonsteroidal anti-inflammatory drugs, with triptans used in moderate to severe headaches unresponsive to over-the-counter therapy. Rescue medication including dihydroergotamine [DHE] should be used for status migrainosus, preferably in the hospital setting. Antiemetics that have antidopaminergic properties can be helpful in patients with associated symptoms of nausea and vomiting through their action on central migraine generation. Furthermore, patients and families should be educated on nonpharmacologic management such as lifestyle modification and avoidance of triggers that can prevent episodic migraine.

Migraines are a common complaint in children and can cause a significant burden to both the child and their families, with a substantial loss in both school and work days, as well as having negative effects on the child’s self-esteem and peer relations. It has become clear that migraine-specific medications are needed in this population of patients and their use may result in a significant improvement of the child’s headaches and quality of life. Rizatriptan benzoate (Maxalt®) is a selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D ) agonist that was approved by the US FDA in 1998 for the acute treatment of migraine attacks in adults. Despite having been widely used in the pediatric population, rizatriptan was most recently approved in December 2011 for pediatric use in children aged 6–17 years. The advantage of rizatriptan over some other triptans is its rapid onset of action, which is thought to be beneficial in the generally shorter migraine attacks of children when compared with adults. It may also be an appealing choice for young children because it comes in an orally disintegrating form for those who may have difficulty in swallowing tablets or who have significant gastrointestinal complaints accompanying their headaches, including nausea, vomiting and abdominal pain.

Summary Background Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000. Methods Updated total numbers of deaths in children aged 0–27 days and 1–59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1–59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates. Findings Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range [UR] 0·916–1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610–0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252–0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977–1·176), diarrhoea (9·9%; 0·751 million, 0·538–1·031), and malaria (7·4%; 0·564 million, 0·432–0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339–0·547], 0·363 million [0·283–0·419], and 0·359 million [0·215–0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4. Interpretation Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010–15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates. Funding The Bill & Melinda Gates Foundation.

Headaches are common in children and adolescents and migraine affects almost 8% of this population. As revisions are made to the ICHD-II criteria to include additional characteristics of pediatric migraine, the diagnosis of migraine is expected to increase. Therefore, it is important to understand and apply successful treatment in acute migraine. Patients and families should be educated about the options for migraine treatment that includes both pharmacologic and conservative behavioral techniques in managing headaches.This review examines the studies that have been performed in pediatric patients, in addition to exploring the treatment options commonly used in pediatrics and adolescents for migraine and their rationale for use.For the acute treatment of migraine, we recommend the use of ibuprofen or acetaminophen for mild, moderate or severe headache. For moderate to severe headache, or for headaches that fail to respond to over-the-counter medications, we recommend the use of a triptan or combination NSAID/triptan therapy. For preventative treament of migraine, cyproheptadine should be reserved for younger children unable to swallow tablets while amitriptyline is preferred due to its once daily dosing and minimal side effects. Topiramate and divalproate are considerable options depending on patient co-morbid profile and preference.

Se presenta el tratamiento de emergencia de una adolescente, sexo femenino, de 11 anos de edad que sufre una fractura corono radicular complicada compleja, y que en forma simultanea presenta fractura radicular oblicua en incisivo central superior derecho. Para exponer la extension subgingival de la fractura, fue necesario levantar un colgajo mucoperiostico. Debido a la exposicion pulpar, y previo a la reposicion de fragmentos con tecnica adhesiva de resina composite, se realizo una terapia pulpar de Cvek. A pesar de existir una extension subgingival de 4-5 mm, no se realizo la extrusion quirurgica ni ortodoncica del fragmento radicular debido a la presencia de fractura radicular oblicua intra-alveolar sin desplazamiento. El manejo clinico conservador y de minima invasion es fundamentado principalmente por la alta capacidad de de cicatrizacion pulpar en dientes permanentes jovenes, la ausencia de desplazamiento entre los fragmentos de la fractura radicular, y la alta capacidad de adhesion y resistencia a la traccion de los sistemas adhesivos actuales. Los controles clinicos y radiograficos durante estos primeros18 meses han mostrado una excelente respuesta pulpar, solo algunas complicaciones periodontales menores en relacion a la invasion del ancho biologico y una adecuado resultado funcional y estetico.

As a case-control study of etiology, the Pneumonia Etiology Research for Child Health (PERCH) project also provides an opportunity to assess the risk factors for severe pneumonia in hospitalized children at 7 sites. We identified relevant risk factors by literature review and iterative expert consultation. Decisions for inclusion in PERCH were based on comparability to published data, analytic plans, data collection costs and logistic feasibility, including interviewer time and subject fatigue. We aimed to standardize questions at all sites, but significant variation in the economic, cultural, and geographic characteristics of sites made it difficult to obtain this objective. Despite these challenges, the depth of the evaluation of multiple risk factors across the breadth of the PERCH sites should furnish new and valuable information about the major risk factors for childhood severe and very severe pneumonia, including risk factors for pneumonia caused by specific etiologies, in developing countries.

Studies in antenatal care clinics suggest that lower genital tract infections (LGTI) may be associated with adverse pregnancy outcomes (APO). We sought to characterize antenatal care patterns and determine whether LGTI are independently associated with preterm birth and/or low-birth weight among a high-risk public sexually transmitted diseases (STD) clinic population.Electronic STD clinic medical records and state birth records were matched for 730 pregnant women age 13 to 49 tested for 5 treatable LGTI (bacterial vaginosis, chlamydia, gonorrhea, early syphilis, and trichomoniasis) in a case-control analysis. Cases were women with preterm and/or low-birth weight newborns; controls were women without APO. The association between LGTI and APO was assessed using logistic regression.Although pregnant women attending STD clinics reported high risk behaviors and were found to have high rates of LGTI (55%), most of these women were engaged in antenatal care (85%). Of the pregnant women, 22% experienced an APO (7% preterm birth, 4% low birth weight, and 12% preterm birth and low birth weight). In multivariate analyses, chlamydia was associated with low-birth weight (adjusted odds ratio [aOR]: 2.07, 95% confidence interval [CI]: 1.01-4.24), and gonorrhea was associated with preterm birth (aOR: 2.01, 95% CI: 1.02-3.97), particularly when diagnosed during the first trimester (aOR: 2.95, 95% CI: 1.30-6.70).Our findings confirm the association of some LGTI with APO and suggest that timing of LGTI screening may affect outcomes. STD clinic visits represent a critical opportunity to target interventions aimed at improving pregnancy outcomes.

BACKGROUND: Our objective was to develop a methodology to estimate causes of death among children age 1-59 months in high child mortality countries without adequate vital registration (VR) systems. METHODS: We systematically reviewed community-based studies reporting at least two causes of death among children 1-59 months of age identified from published and unpublished sources. We included (i) studies conducted after 1979 (ii) for duration of 12 months or an exact multiple (iii) with > or =25 deaths in children

Summary Background Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in children younger than 5 years. Methods We used multicause proportionate mortality models to estimate deaths in neonates aged 0–27 days and children aged 1–59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world. Findings Of the estimated 8·795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5·970 million), with the largest percentages due to pneumonia (18%, 1·575 million, uncertainty range [UR] 1·046 million–1·874 million), diarrhoea (15%, 1·336 million, 0·822 million–2·004 million), and malaria (8%, 0·732 million, 0·601 million–0·851 million). 41% (3·575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1·033 million, UR 0·717 million–1·216 million), birth asphyxia (9%, 0·814 million, 0·563 million–0·997 million), sepsis (6%, 0·521 million, 0·356 million–0·735 million), and pneumonia (4%, 0·386 million, 0·264 million–0·545 million). 49% (4·294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China. Interpretation These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions. Funding WHO, UNICEF, and Bill & Melinda Gates Foundation.

Our goal was to define the risks of preterm birth associated with Chlamydia trachomatis (CT) and other sexually transmitted infections (STIs) among pregnant women. We accessed clinical records from July 2005 to February 2008. The study population included all pregnant women who gave birth to a singleton newborn of at least 20 weeks’ gestation, and who had antenatal care information. We estimated the impact of CT and other STI on the odds of preterm birth using logistic regression. Overall, 2127 women were included in this analysis. The prevalence of CT infection was 4.7%. CT diagnosis was not associated with preterm birth. In conclusion, this study did not find an association between CT and preterm birth. The lack of an association may be explained by early treatment. Future studies evaluating the timing of screening for STIs may help clarify whether pregnant women would benefit more from earlier screening.

OBJECTIVE: To document the use of active management of the third stage of labour for preventing postpartum haemorrhage and to explore factors associated with such use in seven developing countries. METHODS: Nationally representative samples of facility-based deliveries were selected and observed to determine the use of active management of the third stage of labour and associated factors. Policies on active management were assessed through document review and interviews with relevant professionals. FINDINGS: Use of a uterotonic during the third or fourth stages of labour was nearly universal. Correct use of active management of the third stage of labour was found in only 0.5% to 32% of observed deliveries due to multiple deficiencies in practice. In every country except Indonesia, policies regarding active management were conflicting. CONCLUSION: Developing countries have not targeted decreasing postpartum haemorrhage as an achievable goal; there is little use of active management of the third stage of labour, and policies regarding such management often conflict. Studies are needed to identify the most effective components of active management so that the most efficient package of practices can be promoted.

Objective To evaluate factors that influence migraine recurrence after outpatient infusion or inpatient treatment for intractable migraine. Background Recurrence of migraine after acute treatment in an infusion center or an inpatient setting is not well documented in children and adolescents. Given the multifactorial pathogenesis of migraines, multiple factors may influence migraine recurrence. It has been reported that treatment with steroids may reduce the risk of migraine recurrence. The efficacy of steroids as a therapeutic adjunct has not been established. Studies in the adult population have yielded conflicting results. Methods This study is a retrospective chart review of patients presenting for treatment of an intractable migraine to the outpatient infusion unit or inpatient unit at Cincinnati Children's Hospital Medical Center (CCHMC). Data collected included: age, gender, location of treatment (outpatient, inpatient), migraine duration, diagnosis, severity, the addition of steroids to treatment protocols, and recurrence of migraine at 48 and 72 hours after discharge. Data were analyzed using Fisher's exact tests, logistic regression with backward elimination for variable selection, and least squares means slicing with associated odds ratios. Results Charts from 207 pediatric patients were analyzed. Using logistic regression analysis: location, gender, diagnosis, and age were all found to be significant predictors of migraine recurrence (P

Although evidence supports the recommendation for cognitive-behavioral therapy (CBT) for pediatric migraine, few children actually receive this evidence-based intervention. In this article, we briefly review the most recent empirical evidence supporting CBT. We then identify both provider- and system-related barriers as well as patient-related barriers. Finally, we provide practical solutions to addressing these barriers in the service of facilitating children receiving optimal comprehensive management of their headaches.

Background. In the Unites States, long-term care facilities (LTCFs) are the most common setting for norovirus outbreaks. These outbreaks provide a unique opportunity to better characterize the viral and host characteristics of norovirus disease. Methods. We enrolled 43 LTCFs prospectively to study the epidemiology, virology, and genetic host factors of naturally occurring norovirus outbreaks. Acute and convalescent stool, serum, and saliva samples from cases, exposed and nonexposed controls were collected. Norovirus infection was confirmed using quantitative polymerase chain reaction testing of stool samples or 4-fold increase in serum antibody titers. The presence of histo-blood group antigens (secretor, ABO, and Lewis type) was determined in saliva. Results. Sixty-two cases, 34 exposed controls, and 18 nonexposed controls from 10 norovirus outbreaks were enrolled. Forty-six percent of acute, 27% of convalescent case, and 11% of control stool samples tested norovirus positive. Outbreak genotypes were GII. 4 (Den Haag, n = 3; New Orleans, n = 4; and Sydney, n = 2) and GI. 1 (n = 1). Viral load in GII. 4 Sydney outbreaks was significantly higher than in outbreaks caused by other genotypes; cases and controls shed similar amounts of virus. Forty-seven percent of cases shed virus for = 21 days. Symptomatic infections with GII. 4 Den Haag and GII. 4 New Orleans were detected among nonsecretor individuals. Conclusions. Almost half of all symptomatic individuals shed virus for at least 21 days. Viral load was highest in GII. 4 viruses that most recently emerged; these viruses also infect the nonsecretor population. These findings will help to guide development of targeted prevention and control measures in the elderly.

The diagnosis of migraine in the pediatric population is increasing as providers are becoming more familiar with recognizing the condition. Over-the-counter and migraine-specific treatment, once considered off-label, have proven to be effective, especially if given at the early onset of head pain. Mild to severe cases of migraine should be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), with triptans used alone or in combination in moderate to severe headaches unresponsive to over-the-counter therapy. Rescue medication including dihydroergotamine (DHE), a potent vasoconstrictor should be used for intractable migraines and is preferred in the hospital setting. Anti-emetics that have anti-dopaminergic properties can be helpful in patients with associated symptoms of nausea and vomiting along with headache, especially when used in combination therapy. Preventative treatment should be initiated early in patients with frequent headaches to improve headache outcomes and quality of life. Patients and families should be educated on non-pharmacologic management, such as lifestyle modification and avoidance of triggers, that can prevent progression and worsening of migraine.

Because migraine headaches can commonly start in childhood and adolescence, early recognition and establishment of a treatment plan and implementation of lifestyle changes can alter disease progression and ultimately improve the child’s quality of life. Obtaining a thorough history and comprehensive examination is often sufficient to make the diagnosis. However, instances do exist which should alert the clinician to the possibility of a secondary cause of headaches, and appropriate diagnostic testing should be ordered in such situations. Once the diagnosis has been made, an individualized therapeutic approach, taking into account the developmental stage of the child and the high rate of psychiatric and other comorbidities, can be implemented.

The peripheral ameloblastoma is a rare odontogenic soft tissue tumor,1,2 which has been reported to account for approximately 1% to 5% of all ameloblastomas.2,3 It was first described in the literature by Kuru in 1911.4 The tumor is distinguished from its intraosseous counterpart by its extraosseous location and its less aggressive behavior, causing mild saucerization of adjacent bone in some instances, but without actual infiltration into the marrow spaces.1,2,5-7 The peripheral ameloblastoma is thought to arise from rests of the dental lamina or from basal cells of the surface epithelium.1,3,6-8 Histologically, the peripheral ameloblastoma resembles the intraosseous form, consisting of a proliferation of ameloblastic epithelium set in a dense collagenous stroma.1,2,5-7,9 Although the lesion has been reported to appear in acanthomatous, follicular, plexiform, and mixed patterns, there is disparity among authors as to which presentation is predominant, with some studies citing the acanthomatous type5,7,10-12 and a few pointing to the plexiform and follicular types.2,3 The recommended treatment is wide excision down through periosteum.1,7,10 Recurrence has been noted infrequently.2,3,7,8 This report describes a case in which a peripheral ameloblastoma was excised, and a new lesion was observed in the same site approximately one year postoperatively. On biopsy, the specimen exhibited severe dysplastic changes microscopically. Six months later, an additional lesion was noted in the same region, which again proved to be dysplastic histologically. Although a handful of recurrent peripheral ameloblastomas have been documented,10,13-15 even fewer lesions have been noted to undergo malignant transformation.3,7,15 This case is believed to be the first arising in the site of a previously excised peripheral ameloblastoma in which solely dysplasia was seen.

Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist.To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline.A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Children's Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up.Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months.The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0-240 points; 0-10 for little to none, 11-30 for mild, 31-50 for moderate,50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (20 points).At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7-7.7] days; P = .002). The PedMIDAS decreased by 52.7 points for the CBT group vs 38.6 points for the headache education group (difference, 14.1 [95% CI, 3.3-24.9] points; P = .01). In the CBT group, 66% had a 50% or greater reduction in headache days vs 36% in the headache education group (odds ratio, 3.5 [95% CI, 1.7-7.2]; P .001). At 12-month follow-up, 86% of the CBT group had a 50% or greater reduction in headache days vs 69% of the headache education group; 88% of the CBT group had a PedMIDAS of less than 20 points vs 76% of the headache education group. Measured treatment credibility and integrity was high for both groups.Among young persons with chronic migraine, the use of CBT plus amitriptyline resulted in greater reductions in days with headache and migraine-related disability compared with use of headache education plus amitriptyline. These findings support the efficacy of CBT in the treatment of chronic migraine in children and adolescents.clinicaltrials.gov Identifier: NCT00389038.

Background Two of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST). Methods We systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (≥2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST. Results We identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST. Conclusions Few RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines.

OBJECTIVE: To estimate the potential health impact and cost-effectiveness of nationwide Haemophilus influenzae type b (Hib) vaccination in India. STUDY DESIGN: A decision support model was used, bringing together estimates of demography, epidemiology, Hib vaccine effectiveness, Hib vaccine costs, and health care costs. Scenarios favorable and unfavorable to the vaccine were evaluated. State-level analyses indicate where the vaccine might have the greatest impact and value. RESULTS: Between 2012 and 2031, Hib conjugate vaccination is estimated to prevent over 200 000 child deaths (∼1\% of deaths in children

Objectives: The objectives of this study were to assess comorbid psychiatric diagnoses in youth with chronic daily headache (CDH) and to examine relationships between psychiatric status and CDH symptom severity, as well as headache-related disability. Methods: Standardized psychiatric interviews (Kiddie Schedule for Affective Disorders and Schizophrenia, KSADS) were conducted with 169 youth ages 10–17 diagnosed with CDH. Participants provided prospective reports of headache frequency with a daily headache diary and completed measures of symptom severity, headache-related disability (PedMIDAS) and quality of life (PedsQL). Results: Results showed that 29.6% of CDH patients met criteria for at least one current psychiatric diagnosis, and 34.9% met criteria for at least one lifetime psychiatric diagnosis. No significant relationship between psychiatric status and headache frequency, duration, or severity was found. However, children with at least one lifetime psychiatric diagnosis had greater functional disability and poorer quality of life than those without a psychiatric diagnosis. Discussion: Contrary to research in adults with chronic headaches, most youth with CDH did not appear to be at an elevated risk for comorbid psychiatric diagnosis. However, patients with a comorbid psychiatric diagnosis were found to have higher levels of headache-related disability and poorer quality of life. Implications for treatment are discussed.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are emerging as one of the most promising means to prevent pediatric disease. The 7-valent PCV (PCV-7) has been extensively evaluated in clinical trials and recent evidence from the introduction of PCV-7 through national immunization programs has demonstrated impact on pneumococcal disease. METHODS: Clinical trials have shown PCV-7 to be effective against the more severe forms of pneumococcal infections: pneumonia and invasive pneumococcal disease (IPD) as well as overall child mortality. A review shows the tremendous impact PCV-7 has had to date and the potential further benefits of the emerging multi-valent vaccines. RESULTS: Since its introduction the PCV-7 has substantially reduced the incidence of IPD hospital admissions due to pneumonia and acute otitis media in numerous mostly high income low-disease burden countries. The reductions in IPD and pneumonia have also been observed among unvaccinated age groups in countries with routine use of PCV-7 demonstrating that PCV-7 provides herd immunity. Some settings observed an increase in rate of nonvaccine serotype IPD yet rates of overall and vaccine-serotype IPD show marked reductions post-PCV-7 introduction. Limited data are available on the impact of PCV-7 in lower income countries. The available data from efficacy trials from The Gambia and South Africa suggest that PCV-7 will have substantial impact on reducing pneumococcal disease. CONCLUSION: PCV-7 has shown dramatic reduction in disease and mortality rates in the countries in which it has been introduced. The newly introduced 10-valent and 13-valent pneumococcal vaccines are expected to have substantial disease impact but monitoring is essential to determine their true impact and sustain further introduction of pneumococcal conjugate vaccines.

Chronic migraine occurs in about 3% of pediatric headaches. Many would be intractable to more than two preventive medications. OnabotulinumtoxinA has been approved by the US Food and Drug Administration for the use of chronic migraine in adults in 2010. Data on effectiveness and tolerability in the pediatric population are very limited. The study described in this article is a retrospective review of available data of all patients who received OnabotulinumtoxinA for chronic migraine in a large pediatric headache center from 2004 to 2010. Botox is recommended to any pediatric patient coming to the multidisciplinary clinic for chronic headache if they fail two or more preventive medications. This study showed a major change in the frequency of the headache with a statistical difference in the improvement of headache days per month. There was a 30-point drop in the pediatric disability scoring between first injection and follow-up injection with a change from severe disability to moderate disability.

Exacerbation of migraine with menses is common in adolescent girls and women with migraine, occurring in up to 60% of females with migraine. These migraines are oftentimes longer and more disabling and may be related to estrogen levels and hormonal fluctuations.This study identifies the unique genomic expression pattern of menstrual-related migraine (MRM) in comparison to migraine occurring outside the menstrual period and headache-free controls.Whole blood samples were obtained from female subjects having an acute migraine during their menstrual period (MRM) or outside of their menstrual period (non-MRM) and controls (C)--females having a menstrual period without any history of headache. The messenger RNA was isolated from these samples, and genomic profile was assessed. Affymetrix Human Exon ST 1.0 (Affymetrix, Santa Clara, CA, USA) arrays were used to examine the genomic expression pattern differences between these 3 groups.Blood genomic expression patterns were obtained on 56 subjects (MRM = 18, non-MRM = 18, and controls = 20). Unique genomic expression patterns were observed for both MRM and non-MRM. For MRM, 77 genes were identified that were unique to MRM, while 61 genes were commonly expressed for MRM and non-MRM, and 127 genes appeared to have a unique expression pattern for non-MRM. In addition, there were 279 genes that differentially expressed for MRM compared to non-MRM that were not differentially expressed for non-MRM. Gene ontology of these samples indicated many of these groups of genes were functionally related and included categories of immunomodulation/inflammation, mitochondrial function, and DNA homeostasis.Blood genomic patterns can accurately differentiate MRM from non-MRM. These results indicate that MRM involves a unique molecular biology pathway that can be identified with a specific biomarker and suggest that individuals with MRM have a different underlying genetic etiology.