Background and purpose
To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post‐stroke epilepsy.
Methods
This nationwide cohort study was conducted by using data from 2004 to ...2008 on new occurrence of post‐stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan−Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs.
Results
In all, 3622 late‐onset post‐stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person‐months based on ER visits 95% confidence interval (CI) 0.95–1.15 and hospitalizations (95% CI 0.62–0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person‐months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42–0.74; P < 0.001), 0.37 (95% CI 0.18–0.75; P = 0.006) and 0.28 (95% CI 0.15–0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results.
Conclusions
This large nationwide, population‐based study demonstrated that late‐onset post‐stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.
The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more ...pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site.
Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with ...severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio OR, .20; 95% confidence interval CI, .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.
Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological ...profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
Background and purpose
Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia‐associated genes can provide new avenues for stroke prognostic ...applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia‐induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA–messenger RNA (mRNA) biomarkers in addition to using traditional risk factors.
Methods
After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression.
Results
The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa‐let‐7b‐5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system.
Conclusions
Combined analyses of Fas and has‐let‐7b‐5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia‐induced stroke outcomes.
Background. DespiteWorld Health Organization recommendations, the rate of 23-valent pneumococcal (PPV) and influenza (TIV) vaccination among elderly persons in Hong Kong, China, is exceptionally low ...because of doubts about effectiveness of vaccination. The efficacy of dual vaccination remains unknown. Methods. From 3 December 2007 to 30 June 2008, we conducted a prospective cohort study by recruiting outpatients aged ⩾65 years with chronic illness to participate in a PPV and TIV vaccination program. All were observed until 31 March 2009. The outcome of subjects, including the rates of death, hospitalization, pneumonia, ischemic stroke, acute myocardial infarction, and coronary and intensive care admissions, were determined. Results. Of the 36,636 subjects recruited, 7292 received both PPV and TIV, 2076 received TIV vaccine alone, 1875 received PPV alone, and 25,393 were unvaccinated, with a duration of follow-up of 45,834 person-years. Baseline characteristics were well matched between the groups, except that there were fewer male patients in the PPV and TIV group and fewer cases of comorbid chronic obstructive pulmonary disease among unvaccinated persons. At week 64 from commencement of the study, dual-vaccinees experienced fewer deaths (hazard ratio HR, 0.65; 95% confidence interval CI, 0.55–0.77; P <.001) and fewer cases of pneumonia (HR, 0.57; 95% CI, 0.51–0.64; P<.001), ischemic stroke (HR, 0.67; 95% CI, 0.54–0.83; P<.001), and acute myocardial infarction (HR, 0.52; 95% CI, 0.38–0.71; P<.001), compared with unvaccinated subjects. Dual vaccination resulted in fewer coronary (HR, 0.59; 95% CI, 0.44–0.79; P<.001) and intensive care admissions (HR, 0.45; 95% CI, 0.22–0.94; P = .03), compared with among unvaccinated subjects. Conclusions. Dual vaccination with PPV and TIV is effective in protecting elderly persons with chronic illness from developing complications from respiratory, cardiovascular, and cerebrovascular diseases, thereby reducing hospitalization, coronary or intensive care admissions, and death.
Highlights • Children were randomized to 8 months of aerobic exercise or a control program. • Three resting state networks (RSNs) showed greater refinement after exercise. • The motor network showed ...increased synchrony within a frontal brain region. • Exercise may cause more mature patterns of RSN synchrony in overweight children.
Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral ...loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre-treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty-two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 x 10⁸ copies/ml for pandemic H1N1 virus compared with 3.28 x 10⁸ copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT-PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1-7, 2010.
Background. Little is known about the antibody response in natural infection by the novel 2009 influenza A (H1N1) virus and its relationship with clinical and virological parameters. The relative ...lack of background neutralizing antibody against this novel virus provides a unique opportunity for understanding this issue. Methods. Case patients presenting with influenza-like illness who were positive for the pandemic H1 gene by reverse transcription polymerase chain reaction were identified. The serum antibody response was assayed by neutralizing antibody titer (NAT) against the virus in 881 convalescent donors. We retrospectively analyzed clinical parameters and viral load. Results. Ninety percent of the 881 convalescent donors had seroprotective titer of 1:40 or greater. The geometric mean titer of donors with convalescent NAT measured between day 21 and 42 was 1:101.1. Multivariate analysis by ordinal regression showed that pneumonia (odds ratio, 3.39; 95% confidence interval, 1.49–7.61; P = .004) and sputum production (odds ratio, 1.75; 95% CI, 1.01–3.01; P = .046) were the 2 independent factors associated with a higher level of convalescent NAT. Being afebrile on influenza presentation was associated with subsequent poor NAT (<1:40) response ( P = .04). A positive correlation between the nasopharyngeal viral load on presentation and the convalescent NAT was demonstrated (Spearman correlation ρ, 0.238; P = .026). Conclusions. About 10% of these convalescent patients do not have a seroprotective NAT and may benefit from vaccination to prevent reinfection. The convalescent NAT correlated well with the initial viral load and was independently associated with severity of the viral illness, including pneumonia. The findings provide both the clinical and virological markers for identifying potential convalescent plasma donors with high serum NAT, which can be used to produce hyperimmune intravenous immunoglobulin in a randomized treatment trial for patients with severe pandemic H1N1 infection.
Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes.
Initial ...MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and
mutations were established. Histone mutations were also determined (
). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups.
Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3-17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in
-/
(
)-, 14 in
T-/EGFR+, 3 in
+/EGFR-, and 3 in
+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (
= .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (
≤ .048) between patients with H3F3A and HIST1H3B/C mutations.
MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.
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