Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

BACKGROUND: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment. OBJECTIVE: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging. STUDY DESIGN: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks. RESULTS: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001). CONCLUSION: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

Hypnotherapy or medications: a randomized noninferiority trial in urgency urinary incontinent women.

BACKGROUND: Urgency urinary incontinence afflicts many adults, and most commonly affects women. Medications, a standard treatment, may be poorly tolerated, with poor adherence. This warrants investigation of alternative interventions. Mind-body therapies such as hypnotherapy may offer additional treatment options for individuals with urgency urinary incontinence. OBJECTIVE: To evaluate hypnotherapy's efficacy compared to medications in treating women with urgency urinary incontinence. MATERIALS AND METHODS: This investigator-masked, noninferiority trial compared hypnotherapy to medications at an academic center in the southwestern United States, and randomized women with non-neurogenic urgency urinary incontinence to weekly hypnotherapy sessions for 2 months (and continued self-hypnosis thereafter) or to medication and weekly counseling for 2 months (and medication alone thereafter). The primary outcome was the between-group comparison of percent change in urgency incontinence on a 3-day bladder diary at 2 months. Important secondary outcomes were between-group comparisons of percent change in urgency incontinence at 6 and 12 months. Outcomes were analyzed based on noninferiority margins of 5% for between group differences (P < 0.025) (that is, for between group difference in percentage change in urgency incontinence, if the lower bound of the 95% confidence interval was greater than -5%, noninferiority would be proved). RESULTS: A total of 152 women were randomized to treatment between April 2013 and October 2016. Of these women, 142 (70 hypnotherapy, 72 medications) had 3-day diary information at 2 months and were included in the primary outcome analysis. Secondary outcomes were analyzed for women with diary data at the 6-month and then 12-month time points (138 women [67 hypnotherapy, 71 medications] at 6 months, 140 women [69 hypnotherapy, 71 medications] at 12 months. There were no differences between groups' urgency incontinence episodes at baseline: median (quartile 1, quartile 3) for hypnotherapy was 8 (4, 14) and medication was 7 (4, 11) (P = .165). For the primary outcome, although both interventions showed improvement, hypnotherapy did not prove noninferior to medication at 2 months. Hypnotherapy's median percent improvement was 73.0% (95% confidence interval, 60.0-88˖9%), whereas medication's improvement was 88.6% (95% confidence interval, 78.6-100.0%). The median difference in percent change between groups was 0% (95% confidence interval, -16.7% to 0.0%); because the lower margin of the confidence interval did not meet the predetermined noninferiority margin of greater than -5%, hypnotherapy did not prove noninferior to medication. In contrast, hypnotherapy was noninferior to medication for the secondary outcomes at 6 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 75.0-100%; medications, 83.3% improvement, 95% confidence interval, 64.7-100%; median difference in percent change between groups of 0%, 95% confidence interval, 0.0-6.7%) and 12 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 66.7-94.4%; medications, 80% improvement, 95% confidence interval, 54.5-100%; median difference in percent change between groups of 0%, 95% confidence interval, -4.2% to -9.5%). CONCLUSION: Both hypnotherapy and medications were associated with substantially improved urgency urinary incontinence at all follow-up. The study did not prove the noninferiority of hypnotherapy compared to medications at 2 months, the study's primary outcome. Hypnotherapy proved noninferior to medications at longer-term follow-up of 6 and 12 months. Hypnotherapy is a promising, alternative treatment for women with UUI.

Effect of prenatal EPA and DHA on maternal and cord blood insulin sensitivity: a secondary analysis of the mothers, omega 3, and mental health study.

BACKGROUND: We sought to determine whether prenatal supplementation with the omega-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) would increase markers of insulin sensitivity in maternal or cord blood compared with placebo supplementation. A secondary aim was to evaluate the association of serum EPA and DHA fractions with adiponectin, leptin and the adiponectin:leptin ratio (ALR). We hypothesized that omega-3 fatty acid supplementation would increase markers of insulin sensitivity in maternal and umbilical cord plasma. METHODS: We analyzed stored plasma samples collected from a prior 3-arm prospective, double-blinded, randomized controlled trial in which 126 women with singleton pregnancies between 12- and 20-weeks' gestation were randomized to receive: 1) an EPA-rich fish oil supplement, 2) a DHA-rich fish oil supplement, or 3) a soy oil placebo. Maternal venous blood samples were collected at 12-20 weeks gestation (before supplementation) and at 34-36 weeks gestation. At delivery, cord blood was collected. Samples were analyzed using sandwich enzyme-linked immunosorbent assay kits to quantify leptin and adiponectin levels which were utilized to calculate the ALR, a proxy measure for insulin sensitivity. RESULTS: We found no difference in adiponectin, leptin, and the ALR between the treatment and placebo groups at baseline, after supplementation, or in umbilical cord blood. In regression analyses, higher maternal serum DHA fraction was associated with increased ALR before (p = 0.01) and after (p = 0.04) DHA supplementation. There was no association of EPA fraction with any measure of insulin sensitivity. Cord blood DHA fraction was significantly associated with cord plasma leptin (p = 0.02). Early pregnancy BMI was significantly associated with maternal leptin levels at baseline and in late pregnancy (p < 0.001) and was inversely associated with the ALR (p < 0.001). The ALR decreased significantly between the early and late pregnancy visits (p < 0.001). Pregnancy weight gain was inversely associated with the ALR (P. < 0.02). CONCLUSIONS: EPA- and DHA- rich fish oil supplementation had no effect on plasma markers of insulin sensitivity. However, maternal serum DHA fraction was significantly associated with markers of insulin sensitivity. TRIAL REGISTRATION: https://clinicaltrials.gov/, registration number NCT00711971, 7/7/2008.

BP in Dialysis: Results of a Pilot Study.

The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.

Methodology for a trial of brain-centered versus anticholinergic therapy in women with urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: We describe the rationale and methodology for a study comparing mind-body treatment and pharmacotherapy in women with urgency urinary incontinence (UUI). To explore brain associations in UUI, a subset of patients will also undergo functional magnetic resonance imaging (fMRI). We hypothesize that hypnotherapy, a mind-body intervention, will be at least as effective as pharmacotherapy in treating UUI. We also hypothesize that fMRI findings will change following treatment, with changes potentially differing between groups. METHODS: We describe the development and design challenges of a study comparing the efficacy of hypnotherapy and conventional pharmacotherapy in the treatment of UUI. The study randomizes women to either of these treatments, and outcome measures include bladder diaries and validated questionnaires. Sample size estimates, based on a noninferiority test (alpha = 0.025, beta = 0.20), after considering dropout subjects and subjects lost to follow-up, indicated that approximately 150 woman would be required to test the hypothesis that hypnotherapy is not inferior to pharmacotherapy within a 5 % noninferiority margin. The study will also evaluate fMRI changes in a subset of participants before and after therapy. Challenges included designing a study with a mind-body therapy and a comparison treatment equally acceptable to participants, standardizing the interventions, and confronting the reality that trials are time-consuming for participants who have to make appropriate accommodations in their schedule. RESULTS: Study enrollment began in March 2013 and is ongoing. CONCLUSIONS: We describe the design of a randomized controlled trial comparing mind-body therapy and pharmacotherapy in the treatment of UUI and the challenges encountered in its implementation.

INSULIN TIMING: A PATIENT-CENTERED APPROACH TO IMPROVE CONTROL IN TYPE 1 DIABETES.

OBJECTIVE: The goal of insulin therapy in type 1 diabetes (T1D) is to reduce hemoglobin A1C (A1C) to ≤7.0% (53 mmol/mol) with minimal hypoglycemia. We investigated the possibility that "insulin timing" would improve A1C without incurring severe hypoglycemia in volunteers with T1D over a 6-month observation period. METHODS: Forty healthy adult volunteers with T1D were randomly assigned for 6 months to either a control group or an insulin timing group. The primary endpoint was the difference in A1C between the two groups. As a secondary endpoint, both groups were further divided to assess the importance of the baseline A1C in determining the response to timing. The insulin timing algorithm altered the time when the meal dose of insulin was injected or infused from 30 minutes before the meal to 15 minutes after the meal, depending upon the premeal blood glucose concentration. RESULTS: An improvement in mean A1C was observed in the timing group compared with no change in the control group, but this improvement did not reach statistical significance (P>.05). In contrast, when the two groups were analyzed according to baseline A1C, the timing volunteers with baseline A1C values in the upper half (separated by the A1C median of 7.45% [57.9 mmol/mol]) of the timing group had a more robust response to timing (decline in A1C) than the upper half of the control group (P<.05). CONCLUSION: Insulin timing is a patient-centered translational approach that is safe and effective in improving A1C in individuals with T1D with an elevated A1C. ABBREVIATIONS: A1C = hemoglobin A1C ANOVA = analysis of variance CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion MDI = multiple daily injection T1D = type 1 diabetes.

Assessment of Maternal-Infant Interaction: Application of the Still Face Paradigm in a Rural Population of Working Women in Ecuador.

Objectives The importance of mother-child interaction in early infancy on child development has been well documented. The purpose of this study was to assess the feasibility of using the Still Face Paradigm to measure mother interactive style, infant affect and emotional regulation in a rural Ecuador setting. Methods Infant's emotional regulation and the quality of mother's interaction were measured with the Still Face Paradigm at 4 months of age (±15 days). Twenty-four infants and their mothers were assessed in their home. Mother interactive style was coded for attention seeking and contingent responding. Emotional regulation was described by change in infant affect between Still Face episodes. Results A significant difference was found for infant affect between the five Still Face episodes (F1,118 = 9.185, p = 0.003). A significant negative correlation was found for infant affect between episode 3 and 2 with attention seeking mother interactive style during episode 3 (rho = -0.44, p = 0.03), indicating that mothers using more contingent-responding interactions had infants with more positive affect. Conversely, a significant positive association was found for infant affect between episode 3 and 2 and contingent responding mother interactive style during episode 3 (rho = 0.46, p = 0.02), indicating that mothers who used more attention seeking play had infants who showed less positive affect. Conclusion for Practice Study results demonstrate feasibility in using the Still Face Paradigm in working populations residing in a rural region in Ecuadorian highlands and may be feasible in other similar populations in Latin America, and as a successful approach to measuring maternal-child interactions within a field-based epidemiological study design.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project.

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

Epidemiology of mixed, stress, and urgency urinary incontinence in middle-aged/older women: the importance of incontinence history.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is common and the relationship among its subtypes complex. Our objective was to describe the natural history and predictors of the incontinence subtypes stress, urgency, and mixed, in middle-aged and older US women. We tested our hypothesis that UI subtype history predicted future occurrence, evaluating subtype incidence/remission over multiple time points in a stable cohort of women. METHODS: We analyzed longitudinal urinary incontinence data in 10,572 community-dwelling women aged ≥50 in the 2004-2010 Health and Retirement Study. Mixed, stress, and urgency incontinence prevalence (2004, 2006, 2008, 2010) and 2-year cumulative incidence and remissions (2004-2006, 2006-2008, 2008-2010) were estimated. Patient characteristics and incontinence subtype status 2004-2008 were entered into a multivariable, transition model to determine predictors for incontinence subtype occurrence in 2010. RESULTS: The prevalence of each subtype in this population (median age 63-66) was 2.6-8.9 %. Subtype incidence equaled 2.1-3.5 % and remissions for each varied between 22.3 and 48.7 %. Incontinence subtype incidence predictors included ethnicity/race, age, body mass index, and functional limitations. Compared with white women, black women had decreased odds of incident stress incontinence and Hispanic women had increased odds of stress incontinence remission. The age range 80-90 and severe obesity predicted incident mixed incontinence. Functional limitations predicted mixed and urgency incontinence. The strongest predictor of incontinence subtype was subtype history. The presence of the respective incontinence subtypes in 2004 and 2006 strongly predicted 2010 recurrence (odds ratio [OR] stress incontinence = 30.7, urgency OR = 47.4, mixed OR = 42.1). CONCLUSIONS: Although the number of remissions was high, a previous history of incontinence subtypes predicted recurrence. Incontinence status is dynamic, but tends to recur over the longer term.

PERFORMANCE OF A1C VERSUS OGTT FOR THE DIAGNOSIS OF PREDIABETES IN A COMMUNITY-BASED SCREENING.

OBJECTIVE: Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using hemoglobin A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the oral glucose tolerance test (OGTT) for diagnosing prediabetes across Hispanic and non-Hispanic white (NHW) populations. METHODS: A total of 218 asymptomatic adults at risk for type 2 diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes (A1c <5.7% [39 mmol/mol]), prediabetes (A1c 5.7 to 6.4% [46 mmol/mol]), and T2D (A1c >6.4% [46 mmol/mol]). Inclusion criteria were age >18 years and at least one of the following: a family history of diabetes, a history of gestational diabetes, Hispanic ethnicity, non-Caucasian race, or obesity. Subjects received a fasting 75-g OGTT and A1c on the same day. Bowker's test of symmetry was employed to determine agreement between the tests. RESULTS: Data from 99 Hispanic patients and 79 NHW patients were analyzed. There was no concordance between A1c and OGTT for Hispanic (P = .002) or NHW individuals (P = .003) with prediabetes. CONCLUSION: A1c is discordant with OGTT among Hispanic and NHW subjects for the diagnosis of prediabetes. Sole use of A1c to designate glycemic status will result in a greater prevalence of prediabetes among Hispanic and NHW New Mexicans. ABBREVIATIONS: A1c = hemoglobin A1c BMI = body mass index CDC = Centers for Disease Control CI = confidence interval FPG = fasting plasma glucose NHW = non-Hispanic white OGTT = oral glucose tolerance test T2D = type 2 diabetes WHO = World Health Organization.

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Reversible increase in maximal cortisol secretion rate in septic shock.

OBJECTIVE: Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. DESIGN: Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. SETTING: Single academic medical center. PATIENTS: Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). INTERVENTIONS: I.v. cosyntropin (250 µg). MEASUREMENTS AND MAIN RESULTS: Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). CONCLUSIONS: Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials.

OBJECTIVES: Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. METHODS: We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-ß1-42 and phosphorylated-τ181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses. RESULTS: An initial BDS of 6 or greater was significantly correlated with a final diagnosis of BD (p<0.05; area under the curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The most predictive of BD was the factor containing the inflammatory biomarkers of increased BBB permeability, elevated albumin index and reduced MMP-2 index (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD, and combining them improved the diagnostic accuracy. CONCLUSIONS: Biomarkers predicted the diagnosis of the BD type of subcortical ischaemic vascular disease. Using pathophysiological biomarkers to select homogeneous groups of patients needs to be tested in targeted treatment trials.

Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal, crossover design trial.

OBJECTIVES: Methohexital, a barbiturate anesthetic commonly used for electroconvulsive therapy (ECT), possesses dose-dependent anticonvulsant properties, and its use can interfere with effective seizure therapy in patients with high seizure thresholds. Ketamine, an N-methyl-d-aspartate antagonist with epileptogenic properties not broadly used for ECT inductions, is a commonly used induction agent for general anesthesia. Recent studies suggest that the use of ketamine is effective in allowing successful ECT treatment in patients with high seizure thresholds without an increase in adverse effects. In this preliminary study, we directly compared the recovery and reorientation times of subjects receiving ketamine and methohexital for ECTs. METHODS: Twenty patients were randomized in a crossover design to receive methohexital and ketamine for ECT inductions in alternating fashion in 6 trials. Primary outcome measures were recovery time (voluntary movement, respiratory effort, blood pressure, consciousness, and O2 saturation) and reorientation time. Secondary outcome measures were individual recovery variables, adverse effect occurrence, and seizure duration. RESULTS: Overall recovery time was not significantly different between the 2 treatment arms (F(1, 17) = 0.72; P = 0.41). Reorientation time was faster in the methohexital arm (F(1, 17) = 9.23; P = 0.007). CONCLUSION: Ketamine inductions resulted in higher number of adverse effects, higher subject dropout rates, and a longer reorientation time with respect to methohexital inductions. No significant difference in postanesthesia recovery time was found between the ketamine and methohexital arms. Intolerability to ketamine affected a significant proportion of subjects and suggests that ketamine should remain as an alternative or adjunctive agent for patients with high seizure thresholds.

Safety of botulinum toxin for dysphagia in oculopharyngeal muscular dystrophy.

INTRODUCTION: Despite multiple studies reporting marked benefit of botulinum toxin (BTX) for treatment of cricopharyngeal dysphagia, little is known about its safety for this indication. We examined the safety of cricopharyngeal BTX for dysphagia in oculopharyngeal muscular dystrophy (OPMD). METHODS: We reviewed records of patients with OPMD who received cricopharyngeal BTX. RESULTS: Twenty-four patients underwent 66 procedures. Overall adverse event frequency was 44%. The most common adverse events were dysphonia (24%) and worsened dysphagia (14%). Logistic regression demonstrated that dose was a significant predictor of worsened dysphagia (P = 0.036) and of the composite event of dysphonia or worsened dysphagia (P = 0.009). There was a nonsignificant trend for dose as a predictor of dysphonia (P = 0.073). 59% of procedures were associated with symptomatic improvement. CONCLUSIONS: While BTX appears to be beneficial for treatment of dysphagia in OPMD, caution is warranted when injecting the cricopharyngeus muscle due to dose-related risk of dysphonia or worsened dysphagia.

Clinical use of computed tomographic perfusion for the diagnosis and prediction of lesion growth in acute ischemic stroke.

BACKGROUND: Computed tomography perfusion (CTP) mapping in research centers correlates well with diffusion-weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP-derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. METHODS: We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial noncontrast head CT, CTP, CT angiogram (CTA), and follow-up magnetic resonance imaging (MRI) of the brain. The obtained perfusion images were used for image processing. CBV, MTT, and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was conducted using R and SAS software. RESULTS: All normal DWI sequences had normal CBV and MTT studies (N = 89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%) but poor sensitivity (40.0%) for MTT maps predicting positive DWI. The Spearman correlation was significant between MTT and DWI lesions (ρ = 0.66; P > .0001) only for abnormal MTT and DWI lesions >0 cc. CBV lesions did not correlate with final DWI. CONCLUSIONS: In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers.

1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment.

BACKGROUND: White matter hyperintensities (WMHs) are associated with vascular cognitive impairment (VCI) but fail to correlate with neuropsychological measures. As proton MR spectroscopy ((1)H-MRS) can identify ischaemic tissue, we hypothesised that MRS detectable brain metabolites would be superior to WMHs in predicting performance on neuropsychological tests. METHODS: 60 patients with suspected VCI underwent clinical, neuropsychological, MRI and CSF studies. They were diagnosed as having subcortical ischaemic vascular disease (SIVD), multiple infarcts, mixed dementia and leukoaraiosis. We measured brain metabolites in a white matter region above the lateral ventricles with (1)H-MRS and WMH volume in this region and throughout the brain. RESULTS: We found a significant correlation between both total creatine (Cr) and N-acetylaspartyl compounds (NAA) and standardised neuropsychological test scores. Cr levels in white matter correlated significantly with executive function (p=0.001), attention (p=0.03) and overall T score (p=0.007). When lesion volume was added as a covariate, NAA also showed a significant correlation with executive function (p=0.003) and overall T score (p=0.015). Furthermore, while metabolite levels also correlated with total white matter lesion volume, adjusting the Cr levels for lesion volume did not diminish the strength of the association between Cr levels and neuropsychological scores. The lowest metabolite levels and neuropsychological scores were found in the SIVD group. Finally, lesion volume alone did not correlate significantly with any neuropsychological test score. CONCLUSION: These results suggest that estimates of neurometabolite levels provide additional and useful information concerning cognitive function in VCI not obtainable by measurements of lesion load.

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

OBJECTIVES: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. STUDY DESIGN: We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. RESULTS: One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. CONCLUSION: EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.

Glycosylated hemoglobin for diagnosis of prediabetes in acute ischemic stroke patients.

BACKGROUND: Prediabetes (PD) is an independent risk factor for stroke. The American Diabetes Association (ADA) has recently published new guidelines recommending glycosylated hemoglobin A1c (HbA1c) as a marker to diagnose diabetes and PD. Diagnosis of diabetes Mellitus (DM) is often made at the time of hospitalization for stroke. Less is known about identifying PD in acute ischemic stroke (AIS) patients. We aim to investigate the frequency of new-onset PD in the hospitalized AIS patients using the new ADA guidelines. METHODS: We retrospectively studied 362 AIS patients from our local database. Stroke risk factors, type of stroke, and white matter hyperintensities (WMHs) were all collected. Based on the 2010 ADA guidelines, patients were classified as prediabetics, with HbA1c levels of 5.7%-6.4%; diabetics, with HbA1c levels more than 6.5%; and normoglycemic, HbA1c levels less than 5.7%. We used SAS 9.3 for analysis. RESULTS: On admission, 279 (78%) AIS patients had HbA1c values collected. Stratifying by HbA1c, 113 (31%) AIS patients were given the diagnosis of DM and 109 (30%) were given the diagnosis of PD. From the 166 patients with no DM history, 53% had PD and 15% had DM. Patients with DM and PD were more likely to have hypertension (P<.001) and hyperlipidemia (P=.05). The likelihood of new-onset PD increased with age (P<.01). No differences were found by the type of stroke or WMH. CONCLUSION: Diabetes and PD are highly prevalent in the hospitalized ischemic stroke (IS) patients. Our results suggest a need for routine HbA1c testing in all patients with IS. Further larger studies need to confirm these findings.

A randomized, masked study of weekly erythropoietin dosing in preterm infants.

OBJECTIVE: To compare reticulocyte responses of once-per-week erythropoietin (EPO) dosing with 3-times-a-week dosing in preterm infants. STUDY DESIGN: Infants weighing ≤ 1500 g and ≥ 7 days of age were randomized to once-per-week EPO, 1200 U/kg/dose, or 3-times-a-week EPO, 400 U/kg/dose, subcutaneously for 4 weeks, along with iron and vitamin supplementation. Complete blood counts, absolute reticulocyte counts (ARCs), transfusions, phlebotomy losses, and adverse events were recorded. RESULTS: Twenty preterm infants (962 ± 55 g, 27.9 ± 0.4 weeks, 17 ± 3 days of age) were enrolled. Groups were similar at baseline. Infants in both groups had increased ARCs, which were similar between treatment groups at the start and end of 4 weeks. Hematocrit remained stable, and similar numbers of transfusions were administered. No adverse effects of either dosing schedule were noted. CONCLUSIONS: Preterm infants respond to weekly EPO by increasing ARCs and maintaining hematocrit. We speculate that once-per-week EPO dosing might be beneficial to preterm infants requiring increased erythropoiesis.