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Key Points Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131 415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers., Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (, This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia. more...

The purpose of this study was to compare hospitalization outcomes among US inpatients with brain metastases who received stereotactic radiosurgery (SRS) and/or non-SRS radiation therapies without neurosurgical intervention. A cross-sectional study was conducted whereby existing data on 35,199 hospitalization records (non-SRS alone: 32,981; SRS alone: 1035; SRS + non-SRS: 1183) from 2005 to 2014 Nationwide Inpatient Sample were analyzed. Targeted maximum likelihood estimation and Super Learner algorithms were applied to estimate average treatment effects (ATE), marginal odds ratios (MOR) and causal risk ratio (CRR) for three distinct types of radiation therapy in relation to hospitalization outcomes, including length of stay (‘ ≥ 7 days’ vs. ‘ more...

Objective To evaluate the longitudinal relationship in insomnia symptoms over time with incident memory problems and dementia diagnoses among U.S. adults aged 65 years and older. Methods Secondary analyses were performed on 9518 elderly participants (≥65 years) who completed the 2006 wave of the Health and Retirement Study (HRS) and were followed-up to determine if insomnia symptom scores (2006–2014) were associated with time-to-onset of [1] physician-diagnosed “memory-related disease”, “Alzheimer's disease” and/or “dementia, senility or any other serious memory impairment” and [2] diagnosis of dementia based on HRS-specific criteria. Cox proportional hazards models were constructed adjusting for socio-demographic, lifestyle, and health characteristics. Results In fully adjusted models, severe insomnia symptoms were associated with increased risk of physician-diagnosed memory problems. Individuals reporting any change (increase or decrease) in insomnia symptoms during the 2006–2010 period were more likely to be diagnosed with dementia based on HRS criteria. Finally, those who experienced an increase in the severity of insomnia symptoms over time exhibited 41–72% increased risks of physician-diagnosed memory problems and 45–58% increased risks of dementia diagnosis based on HRS criteria. Conclusions When severe insomnia symptoms increased over time, physician-diagnosed memory problems and dementia diagnoses also increased among U.S. elderly people over a 10-year follow-up period. More studies are required to confirm these findings using large prospective cohort designs and validated tools. more...

Co-infection between Helicobacter pylori (Hp) and groups of periodontal pathogens may alter the onset of Alzheimer's disease (AD) and all-cause dementia. We examined the interactive associations among Hp sero-positivity, periodontal disease (Pd), and infections with incident AD and all-cause dementia, among older adults (≥65 years at baseline). Up to 1431 participants from phase 1 of the National Health and Nutrition Survey III (1988-1991) had complete data till January 1st, 2014 on Hp sero-positivity with a mean follow-up of 10-11 years for AD and all-cause dementia incidence. Exposures consisted of 19 periodontal pathogens, constructed factors and clusters, and two Pd markers- probing depth and clinical attachment loss (CAL). Cox proportional hazards models were performed. Around 55% of the selected sample was Hp+. We found that Prevotella intermedia, Campylobacter Rectus, Factor 2 (Pi/Prevotella nigrescens/Prevotella melaninogenica), and the Orange-Red cluster interacted synergistically with Hp sero-positivity, particularly with respect to AD incidence. The presence of higher levels of Actinomyces Naeslundii (An) enhanced the effect of being Hp+ on both AD and all-cause dementia incidence. In contrast, Fusobacterim nucleatum (Fn), and Factor 1 (which included Fn), exhibited an antagonistic interaction with Hp in relation to all-cause dementia. Both probing depth and CAL had direct associations with all-cause dementia among Hp+ individuals, despite nonsignificant interaction. Selected periodontal pathogen titers, factors, and clusters interacted mostly synergistically, with Hp sero-positivity, to alter the risk of AD and all-cause dementia. Ultimately, a randomized controlled trial is needed, examining effects of co-eradication of Hp and select periodontal pathogens on neurodegenerative disease. more...

Purpose Three Chapters of the Commission of the East Mediterranean Affairs (CEMA) of the ILAE conducted a survey to assess the availability of drugs used for the treatment of generalized convulsive status epilepticus (GCSE) across the CEMA countries and to evaluate the treatment choices of adult and pediatric neurologists for the treatment of this condition. Method The web-based survey consisted of two similar vignettes of GCSE in a child and an adult. The questions evaluated the sequential drugs of choice based on drug availability and with the assumption that all drugs were at the disposition of the neurologists. The neurologists were also asked about the timing of introduction of anesthetic drugs and how they monitor patients in drug induced coma. Results Our data showed that the availability of drugs differ substantially across CEMA countries. A benzodiazepine and phenytoin/phenobarbital were the initial drugs of choice for the majority of adults and pediatric neurologists. In cases of refractory status, most neurologists would use a third agent before proceeding to treatment with an anesthetic agent. Although the vast majority would prefer to monitor patients in drug-induced coma with continuous EEG, only 38% are using this modality because of its unavailability at their institutions. Conclusions Our data emphasize that an algorithm for the treatment of GCSE in the CEMA countries should be flexible and should propose different treatment options at each step of the protocol that are based on the best available data while taking into consideration the drug availability across the CEMA countries. more...

Background: To examine patterns and outcomes of bariatric surgeries, including Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB), among women diagnosed with polycystic ovarian syndrome (PCOS). Materials and Methods: Retrospective cohort study using 1998–2011 Nationwide Inpatient Sample data. A total of 52,668 hospital discharge records met eligibility criteria among PCOS women, 18–49 years. Of those, 17,759 had an obesity/overweight diagnosis and 4310 underwent bariatric surgery. Furthermore, 3086 underwent RYGB (n = 2411), LSG (n = 126), or LAGB (n = 549), and were compared to 78,931 non-PCOS controls. Multiple regression models were constructed to examine patient- and hospital-level predictors of obesity/overweight and bariatric surgery, as well as type of bariatric surgery (RYGB, LSG, or LAGB) as a predictor of in-hospital outcomes and PCOS status. Results: The prevalence of obesity/overweight (≈34%) among women diagnosed with PCOS, and of bariatric surgery (≈24%) among women diagnosed with PCOS and obese/overweight varied by patient- and hospital-level characteristics. Women having PCOS and overweight/obesity, who underwent LSG or LAGB, had shorter hospital stay, reduced hospital charges, and better disposition at discharge compared to those who underwent RYGB. PCOS cases and non-PCOS controls experienced similar treatment selection and in-hospital outcomes after bariatric surgery. Also, PCOS cases and non-PCOS controls experienced similar in-hospital outcomes after undergoing RYGB, LSG, or LAGB. Conclusions: Compared to RYGB, LSG and LAGB resulted in improved in-hospital outcomes among obese/overweight PCOS and non-PCOS patients. Further research is needed to examine health care disparities in the context of PCOS, obesity/overweight, and bariatric surgery. more...

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults ( n = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, p < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, p = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, p < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults. more...

Background: As a result of the COVID-19 pandemic first wave, reductions in ST-elevation myocardial infarction (STEMI) invasive care, ranging from 23% to 76%, have been reported from various countries. Whether this change had any impact on coronary angiography (CA) volume or on mechanical support device use for STEMI and post-STEMI mechanical complications in Canada is unknown. Methods: We administered a Canada-wide survey to all cardiac catheterization laboratory directors, seeking the volume of CA use for STEMI performed during the period from March 1 2020 to May 31, 2020 (pandemic period), and during 2 control periods (March 1, 2019 to May 31, 2019 and March 1, 2018 to May 31, 2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects and papillary muscle rupture cases diagnosed, was also recorded. We also assessed whether the number of COVID-19 cases recorded in each province was associated with STEMI-related CA volume. Results: A total of 41 of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (incidence rate ratio [IRR] 0.84; 95% confidence interval 0.80-0.87) in CA for STEMI during the first wave of the pandemic, compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95% confidence interval 0.61-0.89) in the use of intra-aortic balloon pump use for STEMI. Use of an Impella pump and mechanical complications from STEMI were exceedingly rare. Conclusions: We observed a modest 16% decrease in use of CA for STEMI during the pandemic first wave in Canada, lower than the level reported in other countries. Provincial COVID-19 caseload did not influence this reduction. Résumé: Introduction: Après la première vague de la pandémie de COVID-19, de nombreux pays ont déclaré une réduction de 23 % à 76 % des soins invasifs de l'infarctus du myocarde avec élévation du segment ST (STEMI). On ignore si ce changement a entraîné des répercussions sur le volume d'angiographies coronariennes (AC) ou sur l'utilisation des dispositifs d'assistance mécanique lors de STEMI et des complications mécaniques post-STEMI au Canada. Méthodes: Nous avons réalisé un sondage pancanadien auprès de tous les directeurs de laboratoire de cathétérisme cardiaque pour obtenir le volume d'utilisation des AC lors des STEMI réalisées durant la période du 1er mars 2020 au 31 mai 2020 (période de pandémie) et durant 2 périodes témoins (1er mars 2019 au 31 mai 2019 et 1er mars 2018 au 31 mai 2018). Le nombre de dispositifs d'assistance ventriculaire gauche utilisés et le nombre de cas de communications interventriculaires et de ruptures du muscle papillaire diagnostiqués ont également été enregistrés. Nous avons aussi évalué si le nombre de cas de COVID-19 enregistrés dans chaque province était associé au volume d'AC liées aux STEMI. Résultats: Au total, 41 des 42 laboratoires canadiens de cathétérisme (98 %) ont fourni des données. Lors de la comparaison de la première vague de la pandémie aux périodes témoins, nous avons noté une réduction modeste, mais significative, sur le plan statistique de 16 % (ratio du taux d'incidence [RTI] 0,84; intervalle de confiance à 95 % 0,80-0,87) des AC lors de STEMI. Le RTI n’était pas associé au nombre provincial de cas de COVID-19. Nous avons observé une réduction de 26 % (RTI 0,74; intervalle de confiance à 95 % 0,61-0,89) de l'utilisation de pompes à ballonnet intra-aortique lors de STEMI. L'utilisation d'une pompe Impella et les complications mécaniques après les STEMI étaient extrêmement rares. Conclusions: Nous avons observé une diminution modeste de 16 % de l'utilisation des AC lors de STEMI durant la première vague de la pandémie au Canada, soit une diminution plus faible que ce que les autres pays ont signalé. Le nombre provincial de cas de COVID-19 n'a pas influencé cette réduction. more...

The purpose of this study was to evaluate the effectiveness and complication rate of computed tomography (CT)-guided epidural injection of steroids and local anesthetics for pain relief in patients with neuralgia due to acute or chronic herpes zoster (HZ).A prospective study was conducted from April 2017 to February 2019 including patients with HZ neuralgia (HZN) at any stage (acute or chronic, the latter being defined as pain lasting more than 3 months and also called post herpetic neuralgia [PHN]). The sensory ganglion of the affected dermatome and/or the affected sensory nerve was targeted under CT-guidance and local injection of a mixture of two vials of methylprednisolone 40mg/mL and 2mL of Lidocaine 1% was performed. Using a visual analogue scale (VAS, 0 to 10), pain was assessed prior to the procedure, and at day 7, 1 month, 3 months and 6 months. Adverse effects were graded according to the Society of Interventional Radiology classification.Twenty patients were included. There were 9 men and 11 women with a mean age of 67±13.9 (SD) years (range: 27-83 years). Of these, 14 patients had acute HZN and 6 had PHN. Mean VAS at baseline was 8.1±1.2 (SD) (range: 6-10) with significant decrease (P0.0001) at day 7 (3.4±3.2 [SD]; range: 0-10), day 30 (3.4±3.2 [SD]; range: 0-9), day 90 (2.9±3.2 [SD]; range: 0-9), and day 180 (2.5±3.1 [SD]; range: 0-9). Infiltrations were significantly more effective on acute HZN than on PHN (P0.001) and required significantly fewer infiltrations for pain relef (P=0.002). Only one grade A adverse event was reported.Epidural injection of a mixture of steroids and local anesthetics under CT-guidance is effective on HZN with a persisting effect over 6 months. more...

BACKGROUND AND PURPOSE: There is a paucity of data regarding the incidence of structural brain lesions in children with new-onset unprovoked seizures. Our aim was to determine the frequencies and types of epileptogenic lesions detected on a dedicated epilepsy protocol MR imaging according to age group, the presence of developmental delay, and the number and types of seizures. MATERIALS AND METHODS: Consecutive children between 6 months and 18 years of age with new-onset unprovoked seizures were included. The frequencies and types of epileptogenic lesions were determined and then stratified according to sex, age groups, the presence of developmental delay, and the number and types of seizures at presentation. Multivariate analysis was used to identify variables significantly associated with the presence of epileptogenic lesions. RESULTS: One thousand children were included. An epileptogenic lesion was identified in 26%, with malformations of cortical development being the most common lesion (32%), followed by hypoxic-ischemic injury (20%) and vascular etiologies (16%). Univariate analysis showed a significant increase in the frequency of epileptogenic lesions with decreasing age, the presence of developmental delay, and the number and types of seizures at presentation. The presence of developmental delay and seizure type at presentation remained significant in a multivariate analysis. CONCLUSIONS: We documented a relatively high rate of epileptogenic lesions in children with new-onset seizures, with the presence of developmental delay and specific seizure types being associated with a higher likelihood of detecting an epileptogenic lesion on neuroimaging. This study fulfills the requirements of the study design recommended by the Practice Committee of the American Academy of Neurology, and we hope that our results will assist the relevant societies and committees in formulating neuroimaging guidelines for children with new-onset seizures. more...

Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6–6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene‐addicted lung cancers, especially those containing ROS proto‐oncogene 1 (ROS1) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1‐mutant non‐small‐cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of life‐threatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation., Suggested mechanism of action of tumor‐mediated disseminated intravascular coagulation (DIC). more...

Background In-hospital left ventricular (LV) thrombus following acute ST-elevation myocardial infarction (STEMI) has not been evaluated on a national scale and was the focus of this investigation. Methods We used the 2003 to 2013 Nationwide Inpatient Sample database to identify adults ≥18 years old with a principal diagnosis code of ST-elevation myocardial infarction. Patients were divided into two groups defined by the presence or absence of LV thrombus. Clinical characteristics and in-hospital outcomes were studied using relevant statistics. Multiple linear and logistic regression models were conducted to identify factors associated with LV thrombus. Results Of 1,035,888 STEMI patients hospitalized in the U. S from 2003 to 2013, 1982 (0.2%) developed acute in-hospital LV thrombus. Compared to no LV thrombus, patients with LV thrombus were more likely to have in-hospital complications; acute ischemic and hemorrhagic stroke, acute renal failure, gastrointestinal bleed, cardiogenic shock, in-hospital cardiac arrest and mortality. They also had longer mean length of stay and higher hospital charges. Factors associated with LV thrombus included: anterior/anterolateral STEMI, acute or chronic heart failure with reduced ejection fraction, atrial fibrillation, LV aneurysm, Left heart valvular disease, acute or chronic deep venous thrombosis/pulmonary embolism and alcohol abuse. Patients with LV thrombus were less likely to be female [AOR 0.66, 95% CI (0.51–0.84)]. Conclusion The identification of factors associated with early development of LV thrombus following STEMI, will help direct resources for specific high-risk group and prompt cost-effective therapies. Gender variability in LV thrombus development warrants further investigations. more...

BACKGROUND: Epidemiological evidence suggests that both anemia and elevated red cell distribution width (RDW) are associated with cognitive impairment. However, the interplay between these 2 predictors has been understudied. OBJECTIVES: We examined sex- and anemia-specific associations between RDW and cognitive performance among urban adults in the United States. METHODS: Data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (Baltimore, MD; participants aged 30–65 y at baseline, ∼59% African-American, 45% men) were used. Participants were selected based on the completion of 11 cognitive tasks at baseline (2004–2009) and follow-up (2009–2013) visits (mean time between visits: 4.64 ± 0.93 y) and availability of exposure and covariate data, yielding a sample of between 1526 and 1646 adults out of the initial 3720 adults recruited at baseline. Multiple linear mixed-effects regression models were conducted with RDW as the main exposure of interest and anemia/sex as the key effect modifiers. RESULTS: Overall, high RDWs were linked to poorer baseline performance on the California Verbal Learning Test (CVLT) List A (per 1 unit increase in RDW %, main effect: γ(01 )= −0.369 ± 0.114; P = 0.001) and to slower rates of decline on the CVLT Delayed Free Recall (per 1 unit increase in RDW %, RDW × time: γ(11 )= +0.036 ± 0.013; P = 0.007). Among nonanemic participants, RDWs were consistently associated with poorer baseline performance on the Trailmaking Test, Part A (γ(01 )= +3.11 ± 0.89; P more...

BACKGROUND: Elevated levels of inflammatory biomarkers are consistently associated with chronic conditions, for which periodontitis and sleep are established risk factors. We examined the relationships between periodontitis, hours of sleep and white blood cell (WBC) markers among a nationally representative sample of US adults. METHODS: Cross-sectional study using existing demographic, examination, laboratory and questionnaire data on 11,813 participants (5,814 men and 5,999 women, mean age ± SE; range: 52.74 ± 0.24; 30 to 80 years) from the 2009 to 2014 National Health and Nutrition Examination Surveys. Unadjusted, sex- and age-adjusted, as well as fully adjusted linear and logistic regression models were conducted in addition to generalized structural equations models, while considering sampling design complexity. β, odds ratios with their 95% confidence intervals, indirect effects and mediation proportions were estimated. RESULTS: The weighted mean WBC count was 7,130 cells/μL, with the WBC 5-part differential estimated in terms of percentages of lymphocytes (29.50%), monocytes (7.99%), neutrophils (59.03%), eosinophils (2.84%), and basophils (71.88%). Furthermore, 36.2% of participants reported more...

CONTEXT: Breast cancer (BC) is the most common malignancy among women in the US. Vitamin D status and intakes are thought to be inversely associated with BC occurrence. OBJECTIVES: In our systematic review and meta-analysis, we evaluated evidence linking serum 25(OH)D (both in serum and diet) with breast cancer (BC) occurrence. DATA SOURCES AND EXTRACTION: Only observational studies from databases such as PubMed and Cochrane (January 1st 2000 through March 15th, 2018) were included using PRISMA guidelines. Publication bias and consistency upon replication were assessed, while harmonizing risk ratios (RR, 95% CI) of BC, per fixed increment of 5 exposures [10 ng/mL of 25(OH)D; 100 IU/d for total/dietary vitamin D intakes; vitamin D deficiency; supplement use). RRs were pooled using random effect models. DATA ANALYSIS: Pooled findings from 22 studies suggested a net direct association between 25(OH)D deficiency and BC, with RR(pooled) = 1.91, 95% CI: 1.51–2.41, P < 0.001). Total vitamin D intake (RR(pooled) = 0.99, 95% CI: 0.97–1.00, P = 0.022, per 100 IU/d) and supplemental vitamin D (RR(pooled) = 0.97, 95% CI:0.95–1.00, P = 0.026) were inversely associated with BC. No evidence of publication bias was found; all 5 exposures of interest were consistent upon replication. CONCLUSIONS: 25(OH)D deficiency was directly related to BC while total vitamin D and supplemental vitamin D intakes had an inverse relationship with this outcome. Randomized clinical trials are warranted pending further evidence from primary meta-analyses of observational studies. more...

Seizure threshold‐2 (SZT2) gene variants have been associated with a decrease in seizure threshold resulting in variable phenotypic expressions ranging from mild‐moderate intellectual disabilities without seizures, to an early‐onset epileptic encephalopathy with severe cognitive impairment. In addition, hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down‐slanting palpebral fissures, were present in the majority. We herein report a novel SZT2 variant in one of two siblings both diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). This report is the fourth to document a possible familial case in EIMFS, a condition that was not previously associated with SZT2 variant. This report expands the phenotypic expression of SZT2, corroborates the importance of genetic counseling in some cases of EIMFS, and highlights the efficacy of potassium bromide in controlling the seizures associated with this condition. more...

Background It has been shown that gout is associated with left atrium remodeling and a pro‐inflammatory state leading to the development of atrial fibrillation (AF). There is limited evidence whether gout increases the risk of stroke in patients with AF. We assessed the incidence of gout and the risk of stroke in patients with AF. Methods This is a retrospective cohort study using the 2016 US National Inpatient Sample (NIS) based on ICD‐10 codes. The outcomes of the study were the risk and severity of new stroke in patients with pre‐existing AF and gout. Results In 2016, we identified 3 844 057 patients admitted to the hospitals in NIS with history of AF, of which 240 875 had history of gout. Patients with AF and gout have higher risk of new stroke (OR 2.07 [1.97‐2.19], P, Gout was an independent risk factor in predicting new stroke in patients with AF but did not predict worse stroke outcomes or severity. more...

The military is interested in identifying factors to improve the readiness of service members with traumatic brain injury (TBI). TBI outcome studies have primarily used objective neuropsychological data interpreted using the absolute level of functioning (i.e., high average, average, low average), though research suggests it is also important to consider other objective indices of the relative degree of decline (e.g., mild, moderate, severe) and subjective complaints. The current study determined the predictive ability of objective indices of neuropsychological functioning (i.e., absolute level and the relative degree of decline) and subjective complaints (i.e., Neurobehavioral Symptom Inventory) in terms of military work status (i.e., return to duty, medically disabled, retired) for 113 service members with mild TBI. ANOVAs and post-hoc tests indicated individuals who were able to return to duty had higher absolute indices and lower relative decline scores in working memory and overall intelligence, as well as lower subjective neuropsychological complaints when compared to those who were disabled or retired. Multinomial logistic regression models generally supported these findings, except relative decline scores were not predictive of military work status likely due to issues of collinearity (i.e., relative decline scores are calculated using absolute scores). In conclusion, indices of absolute functioning and subjective neuropsychological impairments appear to be predictors of the ability to return to duty post-TBI in military populations, emphasizing the need to focus on cognitive reserve and emotional resilience as potential interventions. more...

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare autosomal recessive disease that manifests with multiorgan presentation characterized by gastrointestinal, extraocular, and both peripheral and central nervous system involvement. MNGIE is caused by mutation in the TYMP (thymidine phosphorylase) gene, resulting in loss of thymidine phosphorylase enzyme activity. This causes its substrates, thymidine and deoxyuridine, to accumulate in tissues and plasma, while also causing secondary alterations in mitochondrial DNA. To date, more than 80 mutations have been reported in this gene. We present herein the clinical, neuroimaging, electrodiagnostic, and molecular findings of a patient with MNGIE caused by a novel homozygous missense mutation (C1175T > G) of the TYMP gene. more...

ObjectiveTo evaluate whether eculizumab helps patients with anti–acetylcholine receptor–positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.ClinicalTrials.gov IdentifierREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.Classification of EvidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo. more...

ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody–positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18–65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups.ResultsPatients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone.ConclusionsThymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone.Clinicaltrials.gov identifierNCT00294658.Classification of evidenceThis study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone. more...

Project Goals Food insecurity and obesity, although counterintuitive, often co-exist in urban environments. In fact, a recent study found that persistent household food insecurity without hunger was associated with 22% greater odds of child obesity compared to those without persistent food security (P more...

Background: The opioid epidemic’s impact reached an increasing portion of the United States population, including pregnant women.Objectives: We sought to determine the prevalence and factors associ... more...

Objective This study aimed to examine patterns of sleep disorders among hospitalized adults 65 years and older as related to Parkinson's disease (PD) status and to evaluate sex differences in the associations between PD with sleep disorders. Methods A cross-sectional study was conducted using 19,075,169 hospital discharge records (8,169,503 men and 10,905,666 women) from the 2004-2014 Nationwide Inpatient Sample databases. PD and sleep disorder diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification coding. Logistic regression models were constructed for each sleep disorder as a correlate of PD status; adjusted odds ratios (aOR) with their 95% confidence intervals (CIs) were calculated taking into account patient and hospital characteristics. Results Period prevalences of PD and sleep disorder were estimated to be 2.1% and 8.1%, respectively. Most sleep disorder types, with the exception of sleep-related breathing disorders, were positively associated with PD diagnosis. Statistically significant interactions by sex were noted for associations of insomnia (men: aOR = 1.29, 95% CI = 1.24-1.36; women: aOR = 1.17, 95% CI = 1.12-1.22), parasomnia (men: aOR = 3.74, 95% CI = 3.44-4.07; women: aOR = 2.69, 95% CI = 2.44-2.96), sleep-related movement disorder (men: aOR = 1.09, 95% CI = 1.07-1.11; women: aOR = 1.22, 95% CI = 1.20-1.25), and any sleep disorder (men: aOR = 1.06, 95% CI = 1.05-1.08; women: aOR = 1.15, 95% CI = 1.13-1.17) with PD status. Conclusions Overall, hospitalized men are more likely to experience PD with insomnia or parasomnia, whereas hospitalized women are more likely to experience PD with sleep-related movement disorder or any sleep disorder. Prospective cohort studies are needed to replicate these cross-sectional findings. more...

Despite its public health significance, TBI management across US healthcare institutions and patient characteristics with an emphasis on utilization and outcomes of TBI-specific procedures have not been evaluated at the national level. We aimed to characterize top 10 procedure codes among hospitalized adults with TBI as primary diagnosis by injury severity. A Cross-sectional study was conducted using 546, 548 hospitalization records from the 2004 to 2014 Nationwide Inpatient Sample were analyzed. Data elements of interest included injury, patient, hospital characteristics, procedures, in-hospital death and length of stay. Ten top procedure codes were “Closure of skin and subcutaneous tissue of other sites”, “Insertion of endotracheal tube”, “Continuous invasive mechanical ventilation for less than 96 consecutive hours”, “Venous catheterization (not elsewhere classified)”, “Continuous invasive mechanical ventilation for 96 consecutive hours or more”, “Transfusion of packed cells”, “Incision of cerebral meninges”, “Serum transfusion (not elsewhere classified)”, “Temporary tracheostomy”, and “Arterial catherization”. Prevalence rates ranged between 3.1% and 15.5%, with variations according to injury severity and over time. Whereas “Closure of skin and subcutaneous tissue of other sites” was associated with fewer in-hospital deaths and shorter hospitalizations, “Temporary tracheostomy” was associated with fewer in-hospital deaths among moderate-to-severe TBI patients, and “Continuous invasive mechanical ventilation for less than 96 consecutive hours” was associated with shorter hospitalizations among severe TBI patients. Other procedures were associated with worse outcomes. Nationwide, the most frequently reported hospitalization procedure codes among TBI patients aimed at homeostatic stabilization and differed in prevalence, trends, and outcomes according to injury severity. more...

Objectives To prospectively compare the frequencies of depression and anxiety in patients with new onset functional seizures versus two age and gender-matched control groups consisting of patients with new onset epileptic seizures and normal individuals. Methods Consecutive patients, 16 years and older, enrolled in a prospective study for suspected new onset epileptic seizures and diagnosed with documented functional seizures were included. We compared the depression and state and trait anxiety scores using the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) between patients with functional seizures and the other two control groups. Results The 33 patients with functional seizures had significantly higher depression and anxiety scores compared to those with epileptic seizures and normal controls. Twenty patients (60.6%) in the functional seizures group scored in the “depression” range compared to 5/33 (15.2%) in the epileptic seizures and 1/33 (3%) in the control groups. In the functional seizures group, 14/33 (42.4%) had scores in the “state anxiety” range compared to 6/33 (18.2%) and 2/33 (6.1%) in the epileptic seizures and normal control groups, respectively. Similarly, 15/33 (51.5%) of patients in the functional seizures group had scores in the “trait anxiety” range compared to 4/33 (12.1%) and 1/33 (3%) in the epileptic seizures and normal control groups, respectively. Conclusions Our results indicate that patients with new onset functional seizures frequently suffer from depression and anxiety at the time of their initial evaluation. These findings underscore the importance of screening for depression and anxiety in that patient population. more...

Background: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms. Objective: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5–6 years later. Methods: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004–2009) and v2 (2009–2013) exposures and ancillary sMRI data at vscan (2011–2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values. Results: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q more...

Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy. more...

Anemia (blood hemoglobin [Hb]

Background: Infectious agents including periodontal pathogens and their neuroinflammatory sequelae have been at the forefront of Alzheimer's Disease (AD) pathology. We investigated whether periodontal disease (Pd) markers and periodontal pathogens in mid-life are associated with clinical outcomes of cognitive impairment after decades of follow-up. Methods: We conducted a retrospective cohort analysis using data from the third National Health and Nutrition Examination Surveys (NHANES III) linked with restricted mortality and incident outcomes derived from the National Death Index and Medicare data [≥45y, 43% men, Nmax=6,650, 1988-1994 through January 1st, 2014, mean follow-up times (45+, all outcomes): 15-17y]. Outcomes of interest included AD mortality (nmax=102), incidence of AD (nmax=888) and all-cause dementia (nmax=1,737). Exposures included Pd markers [mean clinical attachment loss (CAL) and Probing Depth (PD)] and 19 periodontal pathogens (1988-1994: k=19; 1991-1994 (phase 2): k=2). Multiple Cox proportional hazards models were conducted, stratified by age and sex. Findings: In those ≥65 years old, AD incidence was associated with a composite factor comprised of C. Rectus and P. Gingivalis (Pg) titers (per SD, aHR=1.22; 95% CI, 1.04-1.43, P=0.012), whereas AD mortality risk increased with higher baseline levels in a factor comprised of Pg, P. intermedia, P. nigrescens, F. nucleatum, Cr, S. intermedius, C. ochracea and P. melaninogenica (per SD, aHR=1.46; 95% CI, 1.09-1.96, P=0.017). In both the 55+ and 65+ age groups, the Orange-Red cluster (Pm, Pi, Pn, Pg) was associated with increased AD mortality risk. PD and phase 2 (1991-1994) measured Pg were consistently and directly associated with incident AD among older individuals. Interpretation: Evidence for an association between periodontal pathogens and AD and dementia-related outcomes was stronger for older adults. This study presents information that may inform periodontists who treat older adults and calls for a line of inquiry between practitioners focused on Pd and neurodegenerative processes. Funding Statement: This study was entirely supported by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP). Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: The present study was approved for ethical treatment of participants by the Institutional Review Board of the National Institute on Aging, Intramural Research Program. more...

Background Management of patients with syncope lacks standardization. We sought to assess regional variation in hospitalization rates and resource utilization of patients with syncope. Methods We identified adults with syncope using the Nationwide Emergency Department Sample from years 2006 to 2014. Demographics and comorbidity characteristics were compared across geographic regions in the US. Multiple regression was conducted to compare outcomes. Results 9,132,176 adults presented with syncope. Syncope in the Northeast (n = 1,831,889) accounted for 20.1% of visits; 22.6% in the Midwest (n = 2,060,940), 38.5% in the South (n = 3,527,814) and 18.7% in the West (n = 1,711,533). Mean age was 56 years with 57.7% being female. The Northeast had the highest risk-adjusted hospitalization rate (24.5%) followed by the South (18.6%, ORadj 0.58; 95% CI 0.52–0.65, p Conclusions Significant regional variability in hospitalization rates and ED service charges exist among patients with syncope. Standardizing practices may be needed to reduce variability. more...

Objective. We examined relationships of vitamin D status with over time changes in patterns of sleep in a longitudinal study of Whites and African-American urban middle-aged adults, while further testing effect modification by age group, sex and race and the potential roles of dietary and supplemental vitamin D. Methods. Data on 1,760 middle-aged participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS study: Age range at v2: 33-71y, mean±SD:53.0±8.8, % women: 58.4%, % African-American:60.3%) were used, with complete baseline 25-hydroxyvitamin D [25(OH)D] serum concentration data, initial selected covariates and mediators, and initial and/or follow-up data on five sub-scales (sleep duration, daytime dysfunction, sleep disturbance, sleep latency and sleep quality) of the Pittsburgh Sleep Quality Index. Mean±SD time between initial and follow-up visits: 4.1±1.5 years. Time-interval multiple mixed-effects linear regression models were used. Results. Upon multiple testing adjustment, among Whites, initial 25(OH)D was associated with better sleep duration [25(OH)D × TIME γ±SE: -0.027±0.011, P=0.017] and sleep quality [25(OH)D × TIME γ±SE: -0.026±0.010, P=0.008] over time, with heterogeneity by race found for both relationships (P Limitations. Limitations included small sample size, selection bias, residual confounding and lack of objective sleep measures. Conclusions Vitamin D status, possibly through mechanisms involving sunlight exposure, was linked to a potential improvement in sleep duration and quality among White urban adults. more...

To characterize latent classes of diagnostic and/or treatment procedures among hospitalized U.S. adults, 18–64 years, with primary diagnosis of TBI from 2004–2014 Nationwide Inpatient Samples, latent class analysis (LCA) was applied to 10 procedure groups and differences between latent classes on injury, patient, hospital and healthcare utilization outcome characteristics were modeled using multivariable regression. Using 266,586 eligible records, LCA resulted in two classes of hospitalizations, namely, class I (n = 217,988) (mostly non-surgical) and class II (n = 48,598) (mostly surgical). Whereas orthopedic procedures were equally likely among latent classes, skin-related, physical medicine and rehabilitation procedures as well as behavioral health procedures were more likely among class I, and other types of procedures were more likely among class II. Class II patients were more likely to have moderate-to-severe TBI, to be admitted on weekends, to urban, medium-to-large hospitals in Midwestern, Southern or Western regions, and less likely to be > 30 years, female or non-White. Class II patients were also less likely to be discharged home and necessitated longer hospital stays and greater hospitalization charges. Surgery appears to distinguish two classes of hospitalized patients with TBI with divergent healthcare needs, informing the planning of healthcare services in this target population. more...

Context Serum anti-Müllerian hormone level (AMH) and body mass index may be jointly associated with cardiometabolic risk. Objectives Examine the contribution of AMH to cardiometabolic disturbances by weight status among US adult men. Design Cross-sectional analysis using data from the 1999 to 2004 waves of the National Health and Nutrition Examination Survey. Setting Multistage probability sampling of the noninstitutionalized US population. Participants US men aged ≥18 years. Final analytic sample sizes ranged from 517 to 1063 participants. Main Outcome and Exposure Measures Cardiometabolic disturbances (metabolic syndrome and its components, insulin resistance, diabetes, and chronic inflammation) and AMH were obtained from trained staff and nurses in a mobile examination center or during in-home visits. Results AMH was directly associated with insulin resistance among obese men [OR 1.08 (95% CI 1.00, 1.15); P = 0.046; N = 146], whereas AMH was inversely associated with waist circumference (WC) among obese men [OR 0.95 (95% CI 0.91, 0.99); P = 0.049; N = 146]. An inverse relationship was also observed between categorical AMH and diabetes status [medium vs low AMH; OR 0.19 (95% CI 0.043, 0.84); P = 0.030; N = 145] among obese men, with a strong inverse relationship also detected among overweight men [high vs low AMH; OR 0.011 (95% CI 0.0004, 0.27); P = 0.007; N = 193]. An inverse relationship between continuous AMH and diabetes [OR 0.75 (95% CI: 0.59, 0.93); P = 0.011; N = 193] was also detected among overweight men. Conclusions AMH was associated with specific cardiometabolic risk factors, including WC, diabetes status, and insulin resistance, in overweight and obese US men. more...

Complex processes appear to link sleep duration and quality with dietary patterns. Numerous studies show healthful benefits of the Dietary Approaches to Stop Hypertension (DASH) diet, but few have examined its association with sleep duration or quality. The current study tested cross-sectional associations of DASH diet quality score with sleep quality among adults. Analyses of participants were from the 2005&ndash, 2008 wave of the National Health and Nutrition Examination Surveys (n = 3941 adults &ge, 30 years of age, complete data). We performed sex- and age group-stratified multiple OLS regression analyses with DASH total score and components as main predictors and sleep quality as main outcomes, adjusting sequentially for socio-demographic, behavioral and health-related factors. Sex and age differences in associations of DASH with sleep quality, adjusting for covariates, were also examined by incorporating two-way interaction terms between sex/age and the DASH score in each unstratified model. We found that the DASH diet score was inversely related to poor sleep-related daytime dysfunction adjusted by age, sex, demographic and socio-economic factors. Some sex-specific associations were detected between DASH diet component scores and sleep quality. Notably, the potassium DASH component was inversely associated with Factor 1 (&ldquo, sleepiness and sleep disturbance&rdquo, ) among women. The fiber DASH component was associated with better sleep quality and inversely related to Factor 2 (&ldquo, sleep-related daytime dysfunction&rdquo, ) in younger subjects. This study indicates health benefits of the DASH diet for sleep duration and quality. Future longitudinal studies and randomized placebo-controlled trials are required to ascertain protective effects. more...

Background: Ischemic stroke among hospitalized patients who underwent surgical or endovascular therapies for unruptured intracranial aneurysms (IAs) has not been previously examined in nationally representative samples. Objectives: The purpose of this study is to compare the occurrence and in-hospital outcomes (nonroutine discharge, length of stay) of perioperative ischemic stroke among hospitalized patients diagnosed with unruptured IA across treatment selection [surgical clipping, endovascular coiling, stent- or balloon-assisted coiling (SAC or BAC), combined clipping and coiling]. Methods: A cross-sectional study was conducted using 23,053 hospital discharge records from the 2002-2012 Nationwide Inpatient Sample (NIS). Rates, β coefficients, and odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated accounting for survey design complexity, patient- and hospital-level confounders. Results: Ischemic stroke rate was 6.9% [surgical clipping (4.3%), endovascular coiling (8.1%), BAC or SAC (1.9%), and combined techniques (4.2%)]. Multivariable logistic regression models suggested that compared to patients undergoing surgical clipping alone, those undergoing SAC or BAC were less likely to be diagnosed with ischemic stroke (adjusted OR=0.34, 95% CI: 0.14, 0.85). Compared to clipping, endovascular techniques resulted in fewer nonroutine dispositions and shorter hospitalizations, whereas combined techniques resulted in longer hospitalizations. Differences in hospitalization outcomes between treatment types were only affected by ischemic stroke when comparing coiling to clipping. Conclusions: Perioperative ischemic stroke rate among patients with unruptured IA may be less among those undergoing SAC or BAC as compared to those undergoing surgical clipping alone. Improved in-hospital outcomes among coiling versus clipping recipients may depend on ischemic stroke diagnosis. more...

The aim of this study is to examine how health outcomes varied by treatment selection and race/ethnicity among hospitalized US patients with ruptured or unruptured IAs. A retrospective cohort study was conducted using a sample of 62,224 hospital discharges from the 2002–2012 Nationwide Inpatient Sample. Logistic regression models evaluated treatment selection as predictor of in-hospital survival (IHS: “yes,” “no”) and length of stay (LOS ≤ 7 days, > 7 days), overall and across racial/ethnic groups, taking hospital- and patient-level confounders into account, while stratifying by IA rupture status. Compared to surgical clipping, endovascular coiling was associated with better IHS, after controlling for confounders. Compared to surgical clipping, LOS ≤ 7 days was less likely in patients with combination of treatments and more likely among patients with endovascular coiling as well as balloon- or stent-assisted coiling. Observed relationships varied significantly by race and ethnicity for IHS, but not for LOS ≤ 7 days. Whereas combination of treatments were associated with worse IHS than surgical clipping among Blacks alone, endovascular coiling was associated with better IHS than surgical clipping among White and Other racial/ethnic subgroups. These relationships were for the most part consistent among patients with and without IA rupture. Racial and ethnic subgroups of IA patients experienced differential IHS by treatment selection, irrespective of IA rupture status. Prospective cohort studies are needed to further elucidate these racial and ethnic disparities, while collecting data on IA size, location, and morphology as well as Hunt and Hess grade for ruptured IA. more...

Serum uric acid (SUA), a causative agent for gout, is linked to dietary factors, perhaps differentially by race. Cross-sectional (SUAbase, i.e. baseline SUA) and longitudinal (SUArate; i.e. annual rate of change in SUA) associations of SUA with diet were evaluated across race and sex–race groups, in a large prospective cohort study of urban adults. Of 3720 African American (AA) and White urban adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span study, longitudinal data (2004–2013,k=1·7 repeats, follow-up, 4·64 (sd0·93) years) onn2138 participants were used. The main outcome consisted of up to two repeated measures on SUA. Exposures included the dietary factors such as ‘added sugar’, ‘alcoholic beverages’, ‘red meat’, ‘total fish’, ‘legumes’, ‘total dairy product’, ‘caffeine’, ‘vitamin C’ and a composite measure termed ‘dietary urate index’. Mixed-effects linear regression models were conducted, stratifying by race and by race×sex. A positive association between legume intake and SUAratewas restricted to AA, whereas alcohol intake was positively associated with SUAbaseoverall without racial differences. Added sugars were directly related to SUAbaseamong White men (Prateamong AA women, unlike among White women. Nevertheless, dairy product intake was associated with a lower SUAbaseamong Whites. Finally, the dietary urate index was positively associated with both SUAbaseand SUArate, particularly among AA. In sum, race and sex interactions with dietary intakes of added sugars, dairy products and legumes were detected in determining SUA. Similar studies are needed to replicate these findings. more...

Background Obesity (OB) is a serious epidemic in the United States. Methods We examined OB patterns and time trends across socio-economic and geographic parameters and projected the future situation. Large national databases were used. Overweight (OW), OB and severe obesity (SOB) were defined using body mass index cut-points/percentiles; central obesity (CO), waist circumference cut-point in adults and waist:height ratio cutoff in youth. Various meta-regression analysis models were fit for projection analyses. Results OB prevalence had consistently risen since 1999 and considerable differences existed across groups and regions. Among adults, men’s OB (33.7%) and OW (71.6%) levelled off in 2009–2012, resuming the increase to 38.0 and 74.7% in 2015–2016, respectively. Women showed an uninterrupted increase in OB/OW prevalence since 1999, reaching 41.5% (OB) and 68.9% (OW) in 2015–2016. SOB levelled off in 2013–2016 (men: 5.5–5.6%; women: 9.7–9.5%), after annual increases of 0.2% between 1999 and 2012. Non-Hispanic Blacks had the highest prevalence in women’s OB/SOB and men’s SOB. OB prevalence in boys rose continuously to 20.6% and SOB to 7.5% in 2015–2016, but not in girls. By 2030, most Americans will be OB/OW and nearly 50% of adults OB, whereas ∼33% of children aged 6–11 and ∼50% of adolescents aged 12–19 will be OB/OW. Since 1999, CO has risen steadily, and by 2030 is projected to reach 55.6% in men, 80.0% in women, 47.6% among girls and 38.9% among boys. Regional differences exist in adult OB prevalence (2011–2016) and across ethnicities; South (32.0%) and Midwest (31.4%) had the highest rates. Conclusions US obesity prevalence has been rising, despite a temporary pause in 2009–2012. Wide disparities across groups and geographical regions persist. Effective, sustainable, culturally-tailored interventions are needed. more...

Background Focal cortical dysplasias (FCDs) are highly epileptogenic and frequently associated with medically refractory focal epilepsy. FCDs are frequently located in the frontal lobe, making its complete resection highly challenging when in proximity to the motor cortex. Case Description We report a case of a 25-year-old woman with medically refractory epilepsy secondary to a focal cortical dysplasia in the motor cortex and extending deeply into the subcortical white matter. A detailed presurgical evaluation and invasive electroencephalographic monitoring performed at our epilepsy monitoring unit, along with the use of motor mapping, functional magnetic resonance imaging, diffusion tensor imaging, and the Stealth navigation system resulted in the complete resection of the lesion without a permanent postoperative motor deficit. The patient remained seizure-free at a 63-month follow-up while being maintained on a single antiepileptic drug. Conclusion A detailed presurgical evaluation, accurate mapping of the functional and dysplastic cortex, and a well-planned tailored and complete surgical resection of the cortical dysplasia can result in a favorable outcome with relatively little risk of postoperative neurologic deficit. more...

Objective The aims of this study were to evaluate the frequency of paroxysmal spells of indeterminate nature (PSIN) in a large cohort of children and adults with suspected new‐onset seizures, to evaluate the reasons for including patients in this category, and to calculate the rate of erroneous diagnoses if the epileptologists were compelled to label those events as epileptic seizures or nonepileptic paroxysmal spells. Methods Patients identified for this study participated in a prospective study evaluating patients with suspected new‐onset unprovoked seizures. The workup included a detailed history and a thorough description of the spells, a 3‐hour video EEG recording, and an epilepsy protocol brain MRI. Based exclusively on a detailed description of the ictal events, two epileptologists were asked to independently classify each patient into those with a definite diagnosis of unprovoked seizures or a definite diagnosis of a nonepileptic paroxysmal spells (group 1) and those with PSIN (group 2). Results A total of 1880 consecutive patients were enrolled with 255 (13.6%) included in the PSIN group. Patients with PSIN were significantly younger than those with a definite diagnosis, and PSIN were significantly more frequent in children with developmental delay. The most common reason for including patients in the PSIN group was the inability to categorically discriminate between a seizure and a nonepileptic mimicker. When the raters were compelled to classify the spells in the PSIN group, the frequencies of erroneous diagnoses ranged between 32% and 38%. The final diagnoses on those patients were made based on the results of the EEG, MRI, and follow‐up visits. Significance Our data indicate that a diagnostic category of PSIN should be recognized and ought to be used in clinical practice. Acknowledging this uncertainty will result in lower frequencies of erroneous diagnoses, possible stigma, and potential exposure to unnecessary antiseizure medications. more...

BACKGROUND: Although a direct link between opioid use in obese patients and risk of overdose has not been established, obesity is highly associated with higher risk for opioid/opiate overdose. Evidence for clinical impact of obesity on patients with opioid/opiate overdose is scarce. The aim of this study was to determine effects of obesity on healthcare outcomes and mortality trends in hospitalized patients who presented with opioid/opiate overdose in the United States between 2010 and 2014. DESIGN: Multivariate logistic and linear regression analysis compared clinical outcomes and hospital resource utilization between obese and non-obese patients. Trend analysis of in-hospital mortality was also analyzed. SETTING: United States. PARTICIPANTS: 302,863 adults ?18 years and hospitalized with a principle diagnosis of opioid/opiate overdoses between 2010 and 2014. MEASUREMENTS: Primary measurement was in-hospital mortality. Secondary measurements included respiratory failure, cardiogenic shock, mechanical ventilations/intubations, hospital charges, and length of stay. FINDINGS: Prevalence for in-hospital mortality was lower in patients with obesity (2.2% vs 2.9%). Obese patients had higher adjusted odds for respiratory failure (aOR = 1.7, [(CI) 1.6–1.8]) and mechanical ventilation/intubation (aOR = 1.17, [(CI) 1.10–1.2]). They also had longer length of stays (aMD = 0.4 days, [(CI) 0.25–0.58 days] and higher total hospital charges (aMD = $5,561, [(CI) $3,638-$7,483]. Trends of in-hospital mortality for patients with obesity did not significantly increase (2.1% in 2010 to 2.4% in 2014, p trend=0.37), but significantly increased for non-obese patients (2.4% in 2010 to 3.4% in 2014; p trend more...

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon. more...

The role of dairy foods and related nutrients in cardiometabolic health aetiology is poorly understood. We investigated longitudinal associations between the metabolic syndrome (MetS) and its components with key dairy product exposures. We used prospective data from a bi-racial cohort of urban adults (30–64 years at baseline (n 1371)), the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS), in Baltimore City, MD (2004–2013). The average of two 24-h dietary recalls measured 4–10 d apart was computed at baseline (V1) and follow-up (V2) waves. Annual rates of change (Δ) in dairy foods and key nutrients were estimated. Incident obesity, central obesity and the MetS were determined. Among key findings, in the overall urban adult population, both cheese and yogurt (V1 and Δ) were associated with an increased risk of central obesity (hazard ratio (HR) 1·13; 95 % CI 1·05, 1·23 per oz equivalent of cheese (V1); HR 1·21; 95 % CI 1·01, 1·44 per fl oz equivalent of yogurt (V1)]. Baseline fluid milk intake (V1 in cup equivalents) was inversely related to the MetS (HR 0·86; 95 % CI 0·78, 0·94), specifically to dyslipidaemia–TAG (HR 0·89; 95 % CI 0·81, 0·99), although it was directly associated with dyslipidaemia–HDL-cholesterol (HR 1·10; 95 % CI 1·01, 1·21). Furthermore, ΔCa and ΔP were inversely related to dyslipidaemia–HDL and MetS incidence, respectively, whereas Δdairy product fat was positively associated with incident TAG–dyslipidaemia and HDL-cholesterol–dyslipidaemia and the MetS. A few of those associations were sex and race specific. In sum, various dairy product exposures had differential associations with metabolic disturbances. Future intervention studies should uncover how changes in dairy product components over time may affect metabolic disorders. more...

Elevated blood homocysteine (Hcy) among middle-aged adults can increase age-related disease risk, possibly through other biochemical and hematological markers. We selected markers for hyperhomocysteinemia among middle-aged adults, studied time-dependent Hcy-marker associations and computed highly predictive indices of hyperhomocysteinemia, with cross-sectional and longitudinal validations. We used data from the National Health and Nutrition Examination Survey (NHANES III, phase 2, nmax = 4000), the NHANES 1999&ndash, 2006 (nmax = 10,151) and pooled NHANES (cross-sectional validation). Longitudinal validation consisted of mixed-effects linear regression models (Hcy predicting markers&rsquo, annual rates of change), applied to the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS, n = 227&ndash, 244 participants, k = 2.4 repeats/participant, Agebase: 30&ndash, 65 years) data. Machine learning detected nine independent markers for Hcy &gt, 14 &micro, mol/L (NHANES III, phase 2): older age, lower folate and B-12 status, higher serum levels of creatinine, uric acid, alkaline phosphatase, and cotinine, mean cell hemoglobin and red cell distribution widths (RDW), results replicated in the 1999&ndash, 2006 NHANES [AUC = 0.60&ndash, 0.80]. Indices combining binary markers increased elevated Hcy odds by 6.9&ndash, 7.5-fold. In HANDLS, first-visit Hcy predicted annual increase in creatinine, RDW and alkaline phosphatase, with third-visit index (2013&ndash, 2018) directly predicting Hcy (2004&ndash, 2009). We provide evidence of the internal and external validity of indices composed of several biomarkers that are strongly associated with elevated Hcy. more...

OBJECTIVE: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. METHODS: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. RESULTS: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. INTERPRETATION: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:7 issue:8 pages:1327-1339 ispartof: location:United States status: published more...

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.65]); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68] and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population. ispartof: JOURNAL OF THE NEUROLOGICAL SCIENCES vol:407 ispartof: location:Netherlands status: published more...

Background We compared outcomes of therapeutic plasma exchange (TPE) vs intravenous immunoglobulin (IVIG) among hospitalized patients diagnosed with Guillain-Barre syndrome (GBS). Methods In a retrospective cohort study of 6642 records (2637 TPE and 4005 IVIG) from the 2002-2014 Nationwide Inpatient Sample, treatment type was examined as predictor of length of stay, total charges, and in-hospital death, with regression modeling using risk adjustment and propensity scoring to control for confounders. Results Compared with those receiving IVIG, patients who underwent TPE experienced prolonged hospitalization by approximately 7.5 days, greater hospitalization costs by approximately $46,000, and increased in-hospital death with an odds ratio of 2.78. Results did not change after controlling for confounders through risk adjustment, propensity score adjustment, or matching. Conclusions TPE may be associated with poorer healthcare utilization outcomes vs IVIG, although confounding by indication could not be ascertained. more...

Barrett's esophagus (BE) is a predisposing factor of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma (ECA/GEJ Aca). BE patients are stratified and subsequently monitored according to the risk of malignant progression by the combination of endoscopy and biopsy. This study is to evaluate the maspin expression patterns as early diagnostic markers of malignancy in BE patients. Immunohistochemistry (IHC) staining was performed on 62 archival core biopsies from 35 patients, including BE without dysplasia (intestinal metaplasia, IM), BE with low grade dysplasia, BE with high grade dysplasia, carcinoma in situ, and well to poorly differentiated ECA/GEJ Aca (PD-ECA/GEJ Aca). The intensity and the subcellular distribution of immunoreactivity were evaluated microscopically. Statistical analysis was performed using the χ2 and Fisher exact tests. The level of epithelial-specific tumor suppressor maspin protein inversely correlated with the progression from IM to PD-ECA/GEJ Aca. Lesions of each pathological grade could be divided into subtypes that exhibited distinct maspin subcellular distribution patterns, including nuclear only (Nuc), combined nuclear and cytoplasmic (Nuc+Cyt), cytoplasmic only (Cyt) and overall negligible (Neg). The Cyt subtype, which was minor in both IM and dysplasia (approximately 10%), was predominant in ECA/GEJ Aca as early as well-differentiated lesions (more than 50%: p = 0.0092). In comparison, nuclear staining of the tumor suppressor TP53 was heterogeneous in dysplasia, and did not correlate with the differentiation grades of ECA/GEJ Aca. The Cyt subtype of maspin expression pattern in core biopsies of BE patients may serve as a molecular marker for early diagnosis of ECA/GEJ Aca. This work was supported by the NIH grant P30CA022453 (to the Karmanos Cancer Institute with Sheng, S. as a program leader), the Ruth Sager Memorial Fund (to Sheng, S.), the Karmanos Cancer Institute Pilot Project Grant 25S5Z (to Sheng, S.), and the Karmanos Cancer Institute Prostate Cancer Research Pilot Project Grant (to Sheng, S.). more...