Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies

<p><b>Background and Purpose:</b> Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas trials were prospectively designed, randomized, placebo-controlled trials of gavestinel, a glycine-site antagonist and putative neuroprotectant drug administered within 6 hours of suspected ischemic or hemorrhagic stroke. Both trials reported that gavestinel was ineffective in ischemic stroke. This analysis reports the results in those with primary intracerebral hemorrhage.</p> <p><b>Methods:</b> The primary hypothesis was that gavestinel treatment did not alter outcome, measured at 3 months by the Barthel Index (BI), from acute intracerebral hemorrhage, based on pooled results from both trials. The BI scores were divided into 3 groups: 95 to 100 (independent), 60 to 90 (assisted independence), and 0 to 55 (dependent) or dead.</p> <p><b>Results:</b> In total, 3450 patients were randomized in GAIN International (N=1804) and GAIN Americas (N=1646). Of these, 571 were ultimately identified to have spontaneous intracerebral hematoma on baseline head computerized tomography scan. The difference in distribution of trichotomized BI scores at 3 months between gavestinel and placebo was not statistically significant (P=0.09). Serious adverse events were reported at similar rates in the 2 treatment groups.</p> <p><b>Conclusions:</b> These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. These findings are similar to results previously reported in patients with ischemic stroke.</p&gt

Rapidly Progressive Toxic Leukoencephalomyelopathy with Myelodysplastic Syndrome: a Clinicopathological Correlation

Neurological disorders induced by long-term exposure to organic solvents typically have a slowly progressive clinical course, which may be arrested or even reversed following discontinuation of exposure. We report an unusual case of rapidly progressive toxic leukoencephalomyelopathy in a 29-year-old man who had worked at a chemical factory that used toluene for the manufacture of nylon 66 for 5 years. He presented with progressive weakness of legs, recurrent seizures, and cognitive decline. Widespread white-matter changes in the brain and spinal cord, and myelodysplastic syndrome were noted. He died 6 months after the onset of his symptoms, and autopsy showed discrete multifocal demyelination and necrosis in the central nervous system, and dysplastic cells of erythroid, myeloid, and megakaryotic lineages in blood vessels. The co-occurrence of leukoencephalomyelopathy and myelodysplastic syndrome highlights the vulnerability of the white matter and bone marrow to injury from organic solvents. Intravascular congestion of dysplastic hematopoietic cells might have led to his unusually rapid progression of leukoencephalomyelopathy

Attribution of physical complaints to the air disaster in Amsterdam by exposed rescue workers: an epidemiological study using historic cohorts

BACKGROUND: In 1992 a cargo aircraft crashed into a residential area of Amsterdam. A troublesome aftermath followed, with rumors on potential toxic exposures and health consequences. Health concerns remained even though no excess morbidity was predicted in retrospective risk evaluations. This study aimed to assess to what extent the rescue workers attribute long-term physical complaints to this disaster, including its aftermath, and to examine associations between such attribution and types of exposure and background variables. METHODS: Historic cohort study that collected questionnaire data on occupational disaster exposure, attribution of physical complaints, and background variables on average 8.5 years post-disaster. For the present study the workers who were exposed to the disaster were selected from the historic cohort, i.e. the professional firefighters (n = 334), police officers (n = 834), and accident and wreckage investigators (n = 241) who performed disaster-related tasks. RESULTS: Across the three occupational groups, a consistent percentage (ranging from 43% to 49%) of exposed workers with long-term physical complaints attributed these to the disaster, including its aftermath. Those with more physical complaints attributed these to a stronger degree. Multivariate logistic regression analyses showed that attribution was significantly more often reported by firefighters who rescued people, and by police officers who reported the identification and recovery of or search for victims and human remains, clean-up, or security and surveillance of the disaster area; who witnessed the immediate disaster scene; who had a close one affected by the disaster; and who perceived the disaster as the worst thing that ever happened to them. Age, sex and educational level were not significantly associated with attribution. CONCLUSION: This study provides further cross-sectional evidence for the role of causal attribution in post-disaster subjective physical health problems. After on average 8.5 years, almost a third (32%) of all the exposed workers, and almost half (45%) of the exposed workers with physical complaints, attributed these complaints to the disaster, including its aftermath. The similarity of the results across the occupational groups suggests a general rather than an occupation-specific attribution process. Longitudinal studies are needed to determine whether causal disaster attribution leads to persistence of post-disaster complaints and health care utilization

Re-examination of the Controversial Coexistence of Traumatic Brain Injury and Posttraumatic Stress Disorder: Misdiagnosis and Self-Report Measures

The coexistence of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) remains a controversial issue in the literature. To address this controversy, we focused primarily on the civilian-related literature of TBI and PTSD. Some investigators have argued that individuals who had been rendered unconscious or suffered amnesia due to a TBI are unable to develop PTSD because they would be unable to consciously experience the symptoms of fear, helplessness, and horror associated with the development of PTSD. Other investigators have reported that individuals who sustain TBI, regardless of its severity, can develop PTSD even in the context of prolonged unconsciousness. A careful review of the methodologies employed in these studies reveals that investigators who relied on clinical interviews of TBI patients to diagnose PTSD found little or no evidence of PTSD. In contrast, investigators who relied on PTSD questionnaires to diagnose PTSD found considerable evidence of PTSD. Further analysis revealed that many of the TBI patients who were initially diagnosed with PTSD according to self-report questionnaires did not meet the diagnostic criteria for PTSD upon completion of a clinical interview. In particular, patients with severe TBI were often misdiagnosed with PTSD. A number of investigators found that many of the severe TBI patients failed to follow the questionnaire instructions and erroneously endorsed PTSD symptoms because of their cognitive difficulties. Because PTSD questionnaires are not designed to discriminate between PTSD and TBI symptoms or determine whether a patient's responses are accurate or exaggerated, studies that rely on self-report questionnaires to evaluate PTSD in TBI patients are at risk of misdiagnosing PTSD. Further research should evaluate the degree to which misdiagnosis of PTSD occurs in individuals who have sustained mild TBI

Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome

BACKGROUND: Mild traumatic brain injury (MTBI) can sometimes lead to persistent postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has a neural origin, and is related to neurobehavioral deficits. But the evidence is not conclusive. In the attempt to characterise chronic MTBI consequences, the present experiment used a group comparison design, which contrasted persons (a) with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted that participants who have experienced MTBI but show no signs of PCS would perform similar to controls. At the same time, a subgroup of MTBI participants would show PCS symptoms and only these volunteers would have poorer cognitive performance. Thereby, the performance deficits should be most noticeable in participants with highest PCS severity. METHOD: 38 patients with a single MTBI that had occurred at least 12 month prior to testing, and 38 matched controls, participated in the experiment. A combination of questionnaires and neuropsychological test batteries were used to assess the extent of PCS and related deficits in neurobehavioral performance. RESULTS: 11 out of 38 MTBI participants (29%) were found to suffer from PCS. This subgroup of MTBI patients performed poorly on neuropsychological test batteries. Thereby, a correlation was found between PCS symptom severity and test performance suggesting that participants with more pronounced PCS symptoms performed worse in cognitive tasks. In contrast, MTBI patients with no PCS showed performed similar to matched control. We further found that loss of consciousness, a key criterion for PCS diagnosis, was not predictive of sustained PCS. CONCLUSION: The results support the idea that MTBI can have sustained consequences, and that the subjectively experienced symptoms and difficulties in everyday situations are related to objectively measurable parameters in neurocognitive function

Global burden of Clostridium difficile infections::a systematic review and meta-analysis

Background: Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates.Methods: Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model.Results: 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66- 3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient- days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/ y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13- 2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups.Conclusions: Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community.</p

Acute Stroke Imaging Research Roadmap II

No abstract available

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome