Context:
Identifying novel early predictors of metabolic disorders is essential to improving effective primary prevention.
Objectives:
The objectives were to examine the contribution of two measures ...of autonomic imbalance, resting heart rate (RHR) and heart rate variability (HRV), on the development of five metabolic risk outcomes, and on cardiovascular disease, diabetes, and early mortality.
Design:
This study was a secondary analysis of prospective data from Offspring Cohort participants (N = 1882) in the Framingham Heart Study (FHS).
Participants:
Participants at FHS Exam 3 (1983–1987) with 1) age years 18 or older, and 2) data on RHR, HRV, and five measures of metabolic risk (blood pressure, fasting glucose, triglycerides, high-density lipoprotein HDL cholesterol, and body mass index BMI) at three follow-up visits over 12 years. We conducted a backward elimination variable selection procedure on a logistic regression model, using baseline RHR, HRV, age, sex, and smoking status to predict the odds of developing a specific metabolic risk.
Outcomes:
Measures included hyperglycemia, high blood pressure, high triglycerides, low HDL cholesterol, and high BMI over 12 years; incident diabetes, cardiovascular disease, and early mortality over 20 years.
Results:
RHR and HRV, along with sex, age, and smoking were significant predictors of high blood pressure, hyperglycemia, and a diagnosis of diabetes within 12 years. RHR and HRV also predicted the development of cardiovascular disease and early mortality for most of the sample.
Conclusions:
In this community sample two measures of autonomic imbalance predicted multiple poor metabolic outcomes and mortality, making autonomic imbalance a potentially worthy target for intervention studies to reduce risks for cardiovascular disorders, diabetes, and early death.
This meta-analysis compared diagnostic validity of electrocorticographic (ECoG) high-γ modulation (HGM) with electrical stimulation mapping (ESM) for presurgical language localization.
From a ...structured literature search, studies with electrode level data comparing ECoG HGM and ESM for language localization were included in the meta-analysis. Outcomes included global measures of diagnostic validity: area under the summary receiver operating characteristic (SROC) curve (AUC), and diagnostic odds ratio (DOR); as well as pooled estimates of sensitivity and specificity. Clinical and technical determinants of sensitivity/specificity were explored.
Fifteen studies were included in qualitative synthesis, and 10 studies included in the meta-analysis (number of patients 1–17, mean age 10.3–53.6years). Overt picture naming was the most commonly used task for language mapping with either method. Electrocorticographic high-γ modulation was analyzed at 50–400Hz with different bandwidths in individual studies. For ESM, pulse duration, train duration, and maximum current varied greatly among studies. Sensitivity (0.23–0.99), specificity (0.48–0.96), and DOR (1.45–376.28) varied widely across studies. The pooled estimates are: sensitivity 0.61 (95% CI 0.44, 0.76), specificity 0.79 (95% CI 0.68, 0.88), and DOR 6.44 (95% CI 3.47, 11.94). Area under the SROC curve was 0.77. Results of bivariate meta-regression were limited by small samples for individual variables.
Electrocorticographic high-γ modulation is a specific but not sensitive method for language localization compared with gold-standard ESM. Given the pooled DOR of 6.44 and AUC of 0.77, ECoG HGM can fairly reliably ascertain electrodes overlying ESM cortical language sites.
•ECoG high-γ modulation is a specific method for presurgical language localization.•It can reliably ascertain language sites localized by electrical stimulation mapping.•It can be a potentially safer technique for language mapping in selected patients.
The hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct ...acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV. We evaluated the effect of CCR5 blockade or knockdown on HCV replication in Huh7.5JFH1 cells.
Cells were exposed to varying concentrations of maraviroc (CCR5 inhibitor), cenicriviroc (CCR2/CCR5 inhibitor), sofosbuvir (nucleotide polymerase inhibitor), or raltegravir (HIV integrase inhibitor).
HCV RNA was detected utilizing two qualitative strand-specific RT-PCR assays. HCV core antigen and NS3 protein was quantified in the supernatant and cell lysate, respectively. siRNA was utilized to knockdown CCR5 gene expression in hepatocytes. Alternatively, anti-CCR5 antibodies were employed to block the receptor. Supernatant levels of HCV RNA (expressed as fold change) were not reduced in the presence of raltegravir but were reduced 8.55-fold and 12.42-fold with cenicriviroc and maraviroc, respectively. Sofosbuvir resulted in a 16.20-fold change in HCV RNA levels. HCV core and NS3 protein production was also reduced in a dose-dependent manner. Two distinct anti-CCR5 antibodies also resulted in a significant reduction in HCV protein expression, as did siRNA knockdown of CCR5 gene expression.
These data provide evidence that CCR5 modulation could have a significant effect on HCV replication in an in vitro system. Further evaluation of the role of CCR5 inhibition in clinical settings may be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Missed medical appointments are a common problem across specialties. The discontinuity of care leads to unplanned health care utilization, increased costs, and poor health outcomes. Previous studies ...evaluating pediatric epilepsy have shown significant socioeconomic barriers to care. In several specialties, resident clinic no-show rates are higher than faculty clinics because of socioeconomic barriers. We sought to understand the relationship between race, socioeconomic factors, and missed appointments in a pediatric neurology resident clinic at a large tertiary care hospital. Resident clinic encounters for 1 year were extracted and analyzed for missed appointments, socioeconomic factors, and health care utilization. We found that missed appointments occur for 1 in 5 patients and correlate with socioeconomic factors (eg, income and insurance) and race. Race was a more significant factor than socioeconomic factors for missed appointments. These results provide areas to target and track interventions to improve health outcomes in children in pediatric neurology clinics.
Abstract Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder ...(ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body’s primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8–17 years who participated in the pilot study of Regulating Together , a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test–retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.
Drug-resistant epilepsy (DRE) is common in tuberous sclerosis complex (TSC). The role of stiripentol (STP) in seizure treatment in this population is not well understood. This study evaluates the ...efficacy and tolerability of STP in patients with TSC with DRE.
We performed a retrospective review of patients with TSC with DRE. Seizure frequencies at 1 month before (baseline) and 1, 3, 6, and 12 months after STP initiation were collected.
Of the 1492 patients, 13 received STP and the number of patients with ≥50% seizure reduction at 1, 3, 6, and 12 months was 6/13 (46.2%), 4/13 (30.8%), 8/13 (61.5%), and 6/13 (46.2%), respectively. Six patients (46.2%) had favorable outcomes with persistent seizure reduction through 12 months. Their mean (±S.D.) percentage of seizure reduction at 1, 3, 6, and 12 months was 68.1 (±22.0), 71.3 (±23.2), 75.7 (±23.5), and 75.7 (±23.5), respectively. One patient had worsening seizures throughout the STP course. Three patients did not have seizure reduction until after 6 months, and 2 had initial seizure reduction before worsening. Younger age (P value <0.001), early STP treatment (P value <0.001), higher doses (P value = 0.004), and higher baseline seizure frequency (P value = 0.01) were associated with favorable outcomes. Side effects were seen in 85% of our cohort.
About 46% of the patients had favorable outcomes. Younger age, early STP treatment, higher doses, and higher baseline seizure frequency were significantly associated with favorable outcomes.
Introduction/Aims
Management of Duchenne muscular dystrophy (DMD) has entered an era featuring novel treatments. Trackable noninvasive biomarkers could improve disease progression monitoring and drug ...effect detection. Our aim in this study was to measure changes in selected noninvasive biomarkers and assess their relationship to age and motor function.
Methods
We retrospectively studied 555 patients with DMD who had at least 12 months of treatment of glucocorticoids and were not enrolled in trials of potential disease‐modifying therapies. We extracted biomarker data of serum creatine kinase (CK), serum creatinine (Cr), urine Cr, and urine Cr/urine osmolality (osm), as well as functional data for age at loss of ambulation and Functional Motor Scale (FMS) values from patients’ clinical records. Data were analyzed using linear mixed‐model analyses.
Results
CK, serum Cr, urine Cr, and urine Cr/urine osm all decreased with declining motor function. CK consistently decreased and FMS score consistently worsened with age without clear inflection points. There was an increased odds ratio for LOA with lower values of CK, serum Cr, urine Cr, and urine Cr/urine osm, most notably for urine Cr.
Discussion
Although individual biomarker values are challenging to directly apply clinically, our study has demonstrated that trends over time may complement functional measures in the assessment of individuals with DMD. Future studies could elucidate predictive utility of these biomarkers in assessing motor function changes in DMD.
Fragile X Syndrome (FXS) is caused by a trinucleotide expansion leading to silencing of the FMR1 gene and lack of expression of Fragile X Protein (FXP, formerly known as Fragile X Mental Retardation ...Protein, FMRP). Phenotypic presentation of FXS is highly variable, and the lack of reproducible, sensitive assays to detect FXP makes evaluation of peripheral FXP as a source of clinical variability challenging. We optimized a Luminex-based assay to detect FXP in dried blot spots for increased reproducibility and sensitivity by improving reagent concentrations and buffer conditions. The optimized assay was used to quantify FXP in 187 individuals. We show that the optimized assay is highly reproducible and detects a wide range of FXP levels. Mosaic individuals had, on average, higher FXP levels than fully methylated individuals, and trace amounts of FXP were consistently detectable in a subset of individuals with full mutation FXS. IQ scores were positively correlated with FXP levels in males and females with full mutation FXS demonstrating the clinical utility of this method. Our data suggest trace amounts of FXP detectable in dried blood spots of individuals with FXS could be clinically relevant and may be used to stratify individuals with FXS for optimized treatment.
Summary
Purpose
Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal‐onset zone and eloquent cortex in selected patients with medically ...refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure.
Methods
English‐language studies published up to July 2012, reporting such adverse events were reviewed. Outcome measures included demographic variables; surgical protocol including number of subdural electrodes implanted per patient, duration of monitoring, antibiotic, and steroid prophylaxis; and adverse events.
Key Findings
Twenty‐one studies were identified including a total of 2,542 patients. The reported mean number of electrodes per patient and duration of monitoring varied from 52 to 95 and 5 to 17 days, respectively. There is a trend toward more uniform use of antibiotics and steroids in the perioperative period. Neurologic infections (pooled prevalence 2.3%, 95% confidence interval 1.5–3.1), superficial infections (3.0%, 1.9–4.1), intracranial hemorrhage (4.0%, 3.2–4.8), and elevated intracranial pressure (2.4%, 1.5–3.3) were found to be the most common adverse events. Up to 3.5% of patients required additional surgical procedure(s) for management of these adverse events. Increased number of electrodes (≥67) was found to be independently associated with increased incidence of adverse events.
Significance
Although providing critical information for patients with medically refractory epilepsy, subdural grids implantation and invasive EEG monitoring entails risks of infection, hemorrhage, and elevated intracranial pressure. The prevalence estimates, likely to be conservative due to selective reporting, are expected to be helpful in counseling patients.
The objective of our study was to identify the clinical features and imaging findings of abdominal compartment syndrome (ACS) in children.
During the study period, ACS was diagnosed in 50 children, ...14 of whom underwent CT or MRI. We reviewed the medical records of the 50 children to obtain clinical information, such as underlying risk factors, therapeutic approach, and clinical outcome, and we evaluated the CT and MRI examinations of the 14 children. We compared the imaging features of the 14 children with ACS with those of 14 age-matched control subjects who had abdominal distention without ACS.
The most common risk factor of pediatric ACS was increased abdominal contents, particularly bowel dilatation. Among the 50 children, 38 underwent decompressive intervention. The mortality rate was 45% in the group who underwent decompression versus 58% in the group who did not undergo decompression intervention. From a review of the CT and MR images of the 14 patients with these examinations, we found that the most common findings were ascites (86%), basal lung atelectasis (69%), inferior vena cava (IVC) compression (50%), and abnormal enhancement of bowel wall (64%). Compared with the control subjects, the study group with ACS had the following suggestive imaging features: IVC compression (p = 0.001), basal lung atelectasis (p = 0.006), heterogeneous perfusion of the kidneys (p = 0.026), ascites (p = 0.043), and subcutaneous edema (p = 0.053). However, the ratio of maximal anteroposterior-to-transverse abdominal diameter (AT ratio) was not significant (p = 0.565).
A well-known CT finding for ACS, an increased AT ratio, proved not specific for ACS in pediatric patients; rather, IVC compression, basal lung atelectasis, compromised renal perfusion, and ascites should raise suspicion for ACS in children.
PDF
