Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study.

Backgroundn-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health.MethodsRandomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency.FindingsLow-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors.InterpretationIn this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy.Trial registration numberNCT00871377

Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

BACKGROUND: The modified Rankin Scale (mRS) assessment of global disability is the most common primary endpoint in acute stroke trials but lacks granularity (7 broad levels) and is ordinal (scale levels unknown distances apart), which constrains study power. Disability scales that are linear and continuous may better discriminate outcomes, but computerized administration in stroke patients is challenging. We, therefore, undertook to develop a staged use of an ordinal followed by a linear scale practical to use in multicenter trials. METHODS: Consecutive patients undergoing 3-month final visits in the NIH FAST-MAG phase 3 trial were assessed with the mRS followed by 15 mRS level-specific yes-no items of the Academic Medical Center Linear Disability Score (ALDS), a linear disability scale derived using item response theory. RESULTS: Among 55 patients, aged 71.2 (SD ± 14.2), 67% were men and the entry NIHSS was 10.7 (SD ± 9.5). At 90 days, the median mRS score was 3 (IQR, 1-4), and the median ALDS score was 78.8 (IQR, 3.3-100). ALDS scores correlated strongly with 90 days outcome measures, including the Barthel Index (r = 0.92), NIHSS (r = 0.87), and mRS (r = 0.94). ALDS scores also correlated modestly with entry NIHSS (r = 0.38). At 90 days, the ALDS showed greater scale granularity than the mRS, with fewer patients with identical values, 1.9 (SD ± 3.2) vs. 8.0 (SD ± 3.6), p < 0.001. When treatment effect magnitudes were small to moderate, projected trial sample size requirements were 2-12-fold lower when the ALDS rather than the mRS was used as the primary trial endpoint. CONCLUSION: Among patients enrolled in an acute neuroprotective stroke trial, the ALDS showed strong convergent validity and superior discrimination characteristics compared with the modified Rankin Scale and increased projected trial power to detect clinically meaningful treatment benefits

Hospital experience predicts outcomes after high-risk geriatric surgery.

BACKGROUND: Geriatric patients require specialized perioperative care, yet the impact of geriatric surgery proportion (a measure of experience) and geriatric surgery volume, on clinical outcomes is unknown. This study analyzes the association between proportion and volume and clinical outcomes after high-risk geriatric surgery. METHODS: Using the 2014 National Inpatient Sample, hospital encounters for older adults (≥65 years) undergoing high-risk geriatric surgery were identified. Geriatric surgery volume was defined as a hospitals annual volume of geriatric patients undergoing high-risk geriatric surgery. Geriatric surgery proportion was calculated as volume divided by the sum of high-risk surgeries in all ages. Hierarchical multivariable regression models identified predictors of inpatient mortality, postoperative length of stay, and discharge to nursing facility. RESULTS: There were an estimated 514,950 hospital encounters for older adults undergoing high-risk geriatric surgery from 3,115 hospitals. Mean proportion was 0.53 ± 0.19; median volume was 60 cases per year, ranging from 5 to 3,235. After adjustment, comparing the 90th to 10th percentiles, higher proportion was associated with decreased mortality (odds ratio [95% confidence interval] 0.81 [0.73-0.88]; P < .001) and shorter postoperative length of stay (-4.44% (-5.49 to -3.39%); P < .0001). Higher volume was not associated with mortality but was associated with longer length of stay (7.76% [6.75-8.77%]; P < .0001) and decreased discharge to nursing facility (0.87 [0.79-0.95]; P= .003). CONCLUSION: Treatment of geriatric patients at hospitals with the highest proportion of high-risk geriatric surgery, or the most experience, is associated with improved outcomes. High-proportion hospitals should be examined to understand the mechanisms by which better quality geriatric surgical care is achieved, while lower-proportion hospitals may be targets for quality improvement efforts

Optimizing ECG lead selection for detection of prolongation of ventricular repolarization as measured by the Tpeak‐end interval

BackgroundThe Tpeak-end(Tp-e) has not been compared in all 12 ECG leads in healthy adults to determine if the Tp-e varies across leads. If there is variation, it remains uncertain, which lead(s) are preferred for recording in order to capture the maximal Tp-e value.ObjectiveThe purpose of the current study was to determine the optimal leads, if any, to capture the maximal Tp-e interval in healthy young adults.MethodsIn 88 healthy adults (ages 21-38 years), including derivation (n = 21), validation (n = 20), and smoker/vaper (n = 47) cohorts, the Tp-e was measured using commercial computer software (LabChart Pro 8 with ECG module, ADInstruments) in all 12 leads at rest and following a provocative maneuver, abrupt standing. Tp-e was compared to determine which lead(s) most frequently captured the maximal Tp-e interval.ResultsIn the rest and abrupt standing positions, the Tp-e was not uniform among the 12 leads; the maximal Tp-e was most frequently captured in the precordial leads. At rest, grouping leads V2-V4 resulted in detection of the maximum Tp-e in 85.7% of participants (CI 70.7, 99.9%) versus all other leads (p < .001). Upon abrupt standing, grouping leads V2-V6 together, resulted in detection of the maximum Tp-e 85.0% of participants (CI 69.4, 99.9% versus all other leads; p < .001). These findings were confirmed in the validation cohort, and extended to the smoking/vaping cohort.ConclusionIf only a subset of ECG leads will be recorded or analyzed for the Tp-e interval, selection of the precordial leads is preferred since these leads are most likely to capture the maximal Tp-e value

A new biometric: In utero growth curves for metacarpal and phalangeal lengths reveal an embryonic patterning ratio.

OBJECTIVES: The objectives of this study are to develop gestational age-specific growth curves for fetal third metacarpal and phalangeal lengths and to determine if fetal hand proportion is established in utero. METHODS: This prospective cross-sectional study used 2D ultrasound across gestational ages 12 to 39 weeks to evaluate the third fetal metacarpal and phalangeal measurements. Gestational age-specific reference growth curves were developed. Associations between continuous variables were assessed using Spearman correlations (rs ) and restricted cubic splines. A nonlinear biologic regression model was used to predict metacarpal and phalangeal lengths as a function of gestational age. Measurements derived from five cases of thanatophoric dysplasia were used to determine if brachydactyly could be objectified. RESULTS: Fetal metacarpal and phalangeal lengths are highly correlated across gestational age (rs  = 0.96, P < 0.001). The mean fetal metacarpal to phalangeal ratio is constant from gestational age 15 to 39 weeks (rs  = -0.07, P = 0.49). Third-digit metacarpal and phalangeal lengths in thanatophoric dysplasia showed brachydactyly in all cases (5/5), and none of the cases (0/5) demonstrated a normal metacarpal to phalangeal ratio of 0.49. CONCLUSION: We present gestational age-specific reference growth curves for fetal third metacarpal and phalangeal lengths, which may be used to detect brachydactyly. We demonstrate a prenatal metacarpal to phalangeal ratio of 1:2

Visuoconstructional Impairment in Dementia Syndromes

Dementia of the Alzheimer type (DAT) affects most neuropsychological domains including language, memory, and visuo-spatial skills. The latter are usually assessed by poorly quantifiable copying tasks. We assessed constructional abilities using the Developmental Test of Visuomotor Integration (VMI) comprised of a series of model drawings of increasing complexity. Twenty-six patients meeting NINCDS-ADRDA criteria for DAT, 21 normal aged subjects with normal mental status examinations, and 14 patients with vascular dementia were tested. In DAT, we found significant correlations between visuoconstructive ability and memory registration, delayed recall, and language functions such as confrontation naming and word-list generation. Less marked, but significant correlations were found in the vascular dementia group between visuoconstructive ability and memory registration and word-list generation. A few normal elderly subjects were unable to copy the most challenging figures. The study demonstrates that: (1) VMI is a convenient method for quantifying constructional deficits in DAT and other dementing illnesses; (2) constructional deficits are highly correlated with dementia severity and memory and language deficits in DAT; (3) neuropsychological deficits are less highly inter-correlated in vascular dementia than in DAT; and (4) abnormal constructional skills are present in some normal elderly

Predicting the risk of iliofemoral vascular complication in complex transfemoral-TAVR using new generation transcatheter devices.

OBJECTIVE: Design a predictive risk model for minimizing iliofemoral vascular complications (IVC) in a contemporary era of transfemoral-transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: IVC remains a common complication of TF-TAVR despite the technological improvement in the new-generation transcatheter systems (NGTS) and enclosed poor outcomes and quality of life. Currently, there is no accepted tool to assess the IVC risk for calcified and tortuous vessels. METHODS: We reconstructed CT images of 516 propensity-matched TF-TAVR patients using the NGTS to design a predictive anatomical model for IVC and validated it on a new cohort of 609 patients. Age, sex, peripheral artery disease, valve size, and type were used to balance the matched cohort. RESULTS: IVC occurred in 214 (7.2%) patients. Sheath size (p = 0.02), the sum of angles (SOA) (p < .0001), number of curves (NOC) (p < .0001), minimal lumen diameter (MLD) (p < .001), and sheath-to-femoral artery diameter ratio (SFAR) (p = 0.012) were significant predictors for IVC. An indexed risk score (CSI) consisting of multiplying the SOA and NOC divided by the MLD showed 84.3% sensitivity and 96.8% specificity, when set to >100, in predicting IVC (C-stat 0.936, 95% CI 0.911-0.959, p < 0.001). Adding SFAR > 1.00 in a tree model increased the overall accuracy to 97.7%. In the validation cohort, the model predicted 89.5% of the IVC cases with an overall 89.5% sensitivity, 98.9% specificity, and 94.2% accuracy (C-stat 0.842, 95% CI 0.904-0.980, p < .0001). CONCLUSION: Our CT-based validated-model is the most accurate and easy-to-use tool assessing IVC risk and should be used for calcified and tortuous vessels in preprocedural planning

Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review

BackgroundSince large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death.MethodsTo delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3–6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset.ResultsAmong 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3–6) within 3–6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53–5.63, p < 0.0001). Mortality within 3–6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5–6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8–55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8–81.3%) of poststroke dependence or death and 95.6% (CI: 89.0–98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality.ConclusionLVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes