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Isolated Abducens Nerve Palsy: Update on Evaluation and Diagnosis

Elder, Christopher; Hainline, Clotilde; Galetta, Steven L; Balcer, Laura J; Rucker, Janet C
Abducens nerve palsy is a common clinical finding in neurology practice. In many instances, the origin is obvious and management straightforward; however, the list of possible etiologies and mimics is vast and diverse and diagnostic decisions can be challenging and even controversial. This is especially true when the abducens nerve is affected in isolation, since in the current era of cost-effective medicine, it is critical to accurately diagnose etiologies that may lead to major morbidity or mortality with efficiency. Topics for highlighted updates in this review include management of isolated abducens nerve palsy with a high likelihood of a microvascular ischemic etiology; common imaging pitfalls and current state-of-the-art neuroimaging; and abducens palsy mimics.
PMID: 27306521
ISSN: 1534-6293
CID: 2143362

Past Decline Versus Current eGFR and Subsequent ESRD Risk

Kovesdy, Csaba P; Coresh, Josef; Ballew, Shoshana H; Woodward, Mark; Levin, Adeera; Naimark, David M J; Nally, Joseph; Rothenbacher, Dietrich; Stengel, Benedicte; Iseki, Kunitoshi; Matsushita, Kunihiro; Levey, Andrew S; ,
eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).
PMCID:4978053
PMID: 26657867
ISSN: 1533-3450
CID: 5584032

One-hour post-load plasma glucose level during the OGTT predicts mortality: observations from the Israel Study of Glucose Intolerance, Obesity and Hypertension

Bergman, M; Chetrit, A; Roth, J; Dankner, R
AIMS: The relationship between 1- and 2 h glucose levels following an oral glucose tolerance test (OGTT) and long-term mortality was evaluated. METHODS: Over a 33 year period, 2138 individuals were followed for all-cause mortality. Fasting and post-OGTT glucose parameters categorized the cohort according to baseline glycaemic status. Four categories were established according to 1- and 2 h glucose levels (in mg/dl): group A = 1 h 155 and 2 h < 140; group C = 1 h 155 and 2 h = 140-199 (impaired glucose tolerance). Individuals with diabetes at baseline were excluded from the cohort. RESULTS: By August 2013, 51% of the study cohort had died. The worst prognosis occurred in group D (73.8%), followed by groups C (67.5% mortality), B and A (57.9% and 41.6%, respectively). When the 2 h glucose value is 'normal' (<140mg/dl), the 1 h glucose value >155mg/dl is an important predictor of mortality (28% increased risk) compared with group A, controlling for sex, age, smoking, BMI, systolic and diastolic blood pressures. A gradual increased hazard for mortality was seen by study group(hazard ratio = 1.28, 1.60 and 1.76, for groups B, C and D, respectively; group A = reference). CONCLUSIONS: A 1 h glucose value > 155 mg/dl predicts mortality even when the 2 h level is < 140 mg/dl. However, when the 2 h level is in the impaired glucose tolerance range, the hazard for mortality rises significantly independent of the 1 h value. Individuals at risk for developing diabetes could be identified earlier using the 1 h threshold value of 155 mg/dl, which could avert progression to diabetes and increased mortality
PMID: 26996391
ISSN: 1464-5491
CID: 2051912

The 1-hour post-load glucose level is more effective than HbA1c for screening dysglycemia

Jagannathan, Ram; Sevick, Mary Ann; Fink, Dorothy; Dankner, Rachel; Chetrit, Angela; Roth, Jesse; Buysschaert, Martin; Bergman, Michael
AIM: To assess the performance of HbA1c and the 1-h plasma glucose (PG >/= 155 mg/dl; 8.6 mmol/l) in identifying dysglycemia based on the oral glucose tolerance test (OGTT) from a real-world clinical care setting. METHODS: This was a diagnostic test accuracy study. For this analysis, we tested the HbA1c diagnostic criteria advocated by the American Diabetes Association (ADA 5.7-6.4 %) and International Expert Committee (IEC 6.0-6.4 %) against conventional OGTT criteria. We also tested the utility of 1-h PG >/= mg/dl; 8.6 mmol/l. Prediabetes was defined according to ADA-OGTT guidelines. Spearman correlation tests were used to determine the relationships between HbA1c, 1-h PG with fasting, 2-h PG and indices of insulin sensitivity and beta-cell function. The levels of agreement between diagnostic methods were ascertained using Cohen's kappa coefficient (Kappa). Receiver operating characteristic (ROC) curve was used to analyze the performance of the HbA1c and 1-h PG test in identifying prediabetes considering OGTT as reference diagnostic criteria. The diagnostic properties of different HbA1c thresholds were contrasted by determining sensitivity, specificity and likelihood ratios (LR). RESULTS: Of the 212 high-risk individuals, 70 (33 %) were identified with prediabetes, and 1-h PG showed a stronger association with 2-h PG, insulin sensitivity index, and beta-cell function than HbA1c (P < 0.05). Furthermore, the level of agreement between 1-h PG >/= 155 mg/dl (8.6 mmol/l) and the OGTT (Kappa[95 % CI]: 0.40[0.28-0.53]) diagnostic test was stronger than that of ADA-HbA1c criteria 0.1[0.03-0.16] and IEC criteria (0.17[0.04-0.30]). The ROC (AUC[95 % CI]) for HbA1c and 1-h PG were 0.65[0.57-0.73] and 0.79[0.72-0.85], respectively. Importantly, 1-h PG >/= 155 mg/dl (8.6 mmol/l) showed good sensitivity (74.3 % [62.4-84.0]) and specificity 69.7 % [61.5-77.1]) with a LR of 2.45. The ability of 1-h PG to discriminate prediabetes was better than that of HbA1c (AUC: -0.14; Z value: 2.5683; P = 0.01022). CONCLUSION: In a real-world clinical practice setting, the 1-h PG >/= 155 mg/dl (8.6 mmol/l) is superior for detecting high-risk individuals compared with HbA1c. Furthermore, HbA1c is a less precise correlate of insulin sensitivity and beta-cell function than the 1-h PG and correlates poorly with the 2-h PG during the OGTT.
PMID: 26794497
ISSN: 1432-5233
CID: 1922182

The Role of Plasma Triglyceride/High-Density Lipoprotein Cholesterol Ratio to Predict New Cardiovascular Events in Essential Hypertensive Patients

Turak, Osman; Afsar, Baris; Ozcan, Firat; Oksuz, Fatih; Mendi, Mehmet Ali; Yayla, Cagri; Covic, Adrian; Bertelsen, Nathan; Kanbay, Mehmet
Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular outcomes in the general population. The effect of the TG/HDL-C ratio on essential hypertensive patients is unclear. About 900 consecutive essential hypertensive patients (mean age 52.9+/-12.6 years, 54.2% male) who visited our outpatient hypertension clinic were analyzed. Participants were divided into quartiles based on baseline TG/HDL-C ratio and medical records were obtained periodically for the occurrence of fatal events and composite major adverse cardiovascular events (MACEs) including transient ischemic attack, stroke, aortic dissection, acute coronary syndrome, and death. Participants were followed for a median of 40 months (interquartile range, 35-44 months). Overall, a higher quartile of TG/HDL-C ratio at baseline was significantly linked with higher incidence of fatal and nonfatal cardiovascular events. Using multivariate Cox regression analysis, plasma TG/HDL-C ratio was independently associated with increased risk of fatal events (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.13-1.37; P
PMID: 26694089
ISSN: 1751-7176
CID: 2041942

Associations of sleep duration and quality with disinhibited eating behaviors in adolescent girls at-risk for type 2 diabetes

Kelly, Nichole R; Shomaker, Lauren B; Radin, Rachel M; Thompson, Katherine A; Cassidy, Omni L; Brady, Sheila; Mehari, Rim; Courville, Amber B; Chen, Kong Y; Galescu, Ovidiu A; Tanofsky-Kraff, Marian; Yanovski, Jack A
OBJECTIVES:Short sleep duration and daytime sleepiness have been associated with an increased risk for the onset of type 2 diabetes in adults. There has been far less attention to the characterization of sleep in adolescents at-risk for diabetes or to the possible behavioral mechanisms, such as disinhibited eating, through which sleep may affect metabolic functioning. METHODS:We evaluated the associations of sleep duration and daytime sleepiness with a multi-modal assessment of disinhibited eating in 119 adolescent girls at-risk for type 2 diabetes based upon being overweight/obese and having a family history of diabetes. Girls also endorsed mild-to-moderate depressive symptoms. Adolescents reported sleep duration and daytime sleepiness with the Sleep Habits Survey and Children's Sleep Habits Questionnaire. They were administered a series of successive test meals to measure total energy intake and eating in the absence of hunger (EAH). Adolescent binge eating was assessed with the Eating Disorder Examination interview. RESULTS:Accounting for age, race, puberty, body composition, depressive symptoms, and perceived stress, reported sleep duration was positively related to test meal total energy intake (p=0.04), but not to EAH. Adjusting for the same covariates, daytime sleepiness was associated with a greater odds of objective binge eating in the previous month (p=0.009). CONCLUSIONS:In adolescent girls at-risk for type 2 diabetes, reported sleep characteristics are associated with disinhibited eating behaviors that have been linked to excessive weight and adverse metabolic outcomes. Future studies are called for to evaluate these links using objective measures of sleep.
PMCID:4983254
PMID: 27289521
ISSN: 1873-7358
CID: 4940792

The contribution of children's time-specific and longitudinal expressive language skills on developmental trajectories of executive function

Kuhn, Laura J; Willoughby, Michael T; Vernon-Feagans, Lynne; Blair, Clancy B
To investigate whether children's early language skills support the development of executive functions (EFs), the current study used an epidemiological sample (N=1121) to determine whether two key language indicators, vocabulary and language complexity, were predictive of EF abilities over the preschool years. We examined vocabulary and language complexity both as time-varying covariates that predicted time-specific indicators of EF at 36 and 60 months of age and as time-invariant covariates that predicted children's EF at 60 months and change in EF from 36 to 60 months. We found that the rate of change in children's vocabulary between 15 and 36 months was associated with both the trajectory of EF from 36 to 60 months and the resulting abilities at 60 months. In contrast, children's language complexity had a time-specific association with EF only at 60 months. These findings suggest that children's early gains in vocabulary may be particularly relevant for emerging EF abilities.
PMID: 27101154
ISSN: 1096-0457
CID: 2093002

Executive function and early childhood education

Blair, Clancy
Executive function, a term encompassing domain general cognitive processes associated with working memory, inhibitory control, and the flexible shifting of attention is widely studied in research in neuropsychology and cognitive neuroscience. Only within the last two decades have researchers examined the development of these cognitive abilities in typical child populations. A growing body of research indicates that executive function abilities develop rapidly in early childhood, are important contributors to school readiness and early school success, and are highly relevant to early educational programs for children in poverty.
PMCID:6051751
PMID: 30035205
ISSN: 2352-1546
CID: 3215892

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark, David M J; Grams, Morgan E; Matsushita, Kunihiro; Black, Corri; Drion, Iefke; Fox, Caroline S; Inker, Lesley A; Ishani, Areef; Jee, Sun Ha; Kitamura, Akihiko; Lea, Janice P; Nally, Joseph; Peralta, Carmen Alicia; Rothenbacher, Dietrich; Ryu, Seungho; Tonelli, Marcello; Yatsuya, Hiroshi; Coresh, Josef; Gansevoort, Ron T; Warnock, David G; Woodward, Mark; de Jong, Paul E
A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.
PMCID:4978054
PMID: 26657865
ISSN: 1533-3450
CID: 5100282

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Tin, Adrienne; Grams, Morgan E; Ashar, Foram N; Lane, John A; Rosenberg, Avi Z; Grove, Megan L; Boerwinkle, Eric; Selvin, Elizabeth; Coresh, Josef; Pankratz, Nathan; Arking, Dan E
Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.
PMCID:4978050
PMID: 26794963
ISSN: 1533-3450
CID: 5100342