Viewpoint: filovirus haemorrhagic fever outbreaks: much ado about nothing?

The recent outbreak of Marburg haemorrhagic fever in the Democratic Republic of Congo has put the filovirus threat back on the international health agenda. This paper gives an overview of Marburg and Ebola outbreaks so far observed and puts them in a public health perspective. Damage on the local level has been devastating at times, but was marginal on the international level despite the considerable media attention these outbreaks received. The potential hazard of outbreaks, however, after export of filovirus from its natural environment into metropolitan areas, is argued to be considerable. Some avenues for future research and intervention are explored. Beyond the obvious need to find the reservoir and study the natural history, public health strategies for a more timely and efficient response are urgently needed

Organisation of Health Care During an Outbreak of Marburg Haemorrhagic Fever in the Democratic Republic of Congo, 1999.

Organising health care was one of the tasks of the International Scientific and Technical Committee during the 1998-1999 outbreak in Durba/Watsa, in the north-eastern province (Province Orientale), Democratic Republic of Congo. With the logistical support of Médecins sans Frontières (MSF), two isolation units were created: one at the Durba Reference Health Centre and the other at the Okimo Hospital in Watsa. Between May 6th, the day the isolation unit was installed and May 19th, 15 patients were admitted to the Durba Health Centre. In only four of them were the diagnosis of Marburg haemorrhagic fever (MHF) confirmed by laboratory examination. Protective equipment was distributed to health care workers and family members caring for patients. Information about MHF, modes of transmission and the use of barrier nursing techniques was provided to health care workers and sterilisation procedures were reviewed. In contrast to Ebola outbreaks, there was little panic among health care workers and the general public in Durba and all health services remained operational

Neurocognition in adults with intracranial tumors:Does location really matter?

OBJECTIVE: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. METHODS: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p < .001 and p < .05 for voxel- and cluster-level, resp.). RESULTS: A cohort of 179 intracranial tumor patients was included [aged 19-85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20-30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. INTERPRETATION: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved

Prevalence and predictors of cognitive impairment in adult glioma survivors after multimodal therapy

Background Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect. Material and Methods In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as predictors in a linear regression model per outcome (n=12). Results In this cohort, 29 patients (78%) showed a test score below the predefined cutoff on at least one cognitive test. The percentage of patients who showed test-specific cognitive impairment ranged from 8.1% to 56.76% per test. Fine motor skills, verbal memory, processing speed and executive functioning were the most commonly affected cognitive domains. In this study, the variability in processing speed performance was associated with age (TMT A, p=0.03), time since therapy (WAIS-IV coding, p=0.02) and tumour location. In these measures, poorer outcomes were observed with increasing age, longer time since therapy and in patients with gliomas located in the left frontal lobe. Moreover, age showed to be a significant predictor of verbal memory, with poorer outcomes on the HVLT-R delayed recall task with increasing age (p=0.04). Tumour location predicted working memory performance, as patients with right parietal tumours (p=0.03) showed significantly worse on the WAIS-IV digit span task. Conclusion These preliminary data underline the various alterations of neurocognitive functioning in glioma survivors after multimodal therapy. Therefore, future research needs to shift towards a patient-tailored approach. The next step in this study will be to link these neurocognitive data to advanced neuroimaging data to explore the potential predictive value of imaging markers for neural damage and cognitive outcomes, paving the path to innovative treatment planning techniques

Prevalence and predictors of cognitive impairment in adult glioma survivors after multimodal therapy

Background Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect. Material and Methods In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as predictors in a linear regression model per outcome (n=12). Results In this cohort, 29 patients (78%) showed a test score below the predefined cutoff on at least one cognitive test. The percentage of patients who showed test-specific cognitive impairment ranged from 8.1% to 56.76% per test. Fine motor skills, verbal memory, processing speed and executive functioning were the most commonly affected cognitive domains. In this study, the variability in processing speed performance was associated with age (TMT A, p=0.03), time since therapy (WAIS-IV coding, p=0.02) and tumour location. In these measures, poorer outcomes were observed with increasing age, longer time since therapy and in patients with gliomas located in the left frontal lobe. Moreover, age showed to be a significant predictor of verbal memory, with poorer outcomes on the HVLT-R delayed recall task with increasing age (p=0.04). Tumour location predicted working memory performance, as patients with right parietal tumours (p=0.03) showed significantly worse on the WAIS-IV digit span task. Conclusion These preliminary data underline the various alterations of neurocognitive functioning in glioma survivors after multimodal therapy. Therefore, future research needs to shift towards a patient-tailored approach. The next step in this study will be to link these neurocognitive data to advanced neuroimaging data to explore the potential predictive value of imaging markers for neural damage and cognitive outcomes, paving the path to innovative treatment planning techniques

Marburg hemorrhagic fever associated with multiple genetic lineages of virus.

BACKGROUND: An outbreak of Marburg hemorrhagic fever was first observed in a gold-mining village in northeastern Democratic Republic of the Congo in October 1998. METHODS: We investigated the outbreak of Marburg hemorrhagic fever most intensively in May and October 1999. Sporadic cases and short chains of human-to-human transmission continued to occur until September 2000. Suspected cases were identified on the basis of a case definition; cases were confirmed by the detection of virus antigen and nucleic acid in blood, cell culture, antibody responses, and immunohistochemical analysis. RESULTS: A total of 154 cases (48 laboratory-confirmed and 106 suspected) were identified (case fatality rate, 83 percent); 52 percent of cases were in young male miners. Only 27 percent of these men reported having had contact with other affected persons, whereas 67 percent of patients who were not miners reported such contact (P<0.001). Most of the affected miners (94 percent) worked in an underground mine. Cessation of the outbreak coincided with flooding of the mine. Epidemiologic evidence of multiple introductions of infection into the population was substantiated by the detection of at least nine genetically distinct lineages of virus in circulation during the outbreak. CONCLUSIONS: Marburg hemorrhagic fever can have a very high case fatality rate. Since multiple genetic variants of virus were identified, ongoing introduction of virus into the population helped perpetuate this outbreak. The findings imply that reservoir hosts of Marburg virus inhabit caves, mines, or similar habitats

Development and psychometric evaluation of item banks for memory and attention - supplements to the EORTC CAT Core instrument

BackgroundCancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients' functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank.MethodsIn a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration.ResultsItem assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs &gt;= 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format).ConclusionTwo well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making

Establishing reference values for macro- and microvascular measurements in 4-to-5 year-old children of the ENVIR<i>ON</i>AGE prospective birth cohort

Cardiovascular risk factors are usually better tolerated, and can therefore be perceived as less harmful, at a young age. However, over time the effects of these adverse factors may persist or accumulate and lead to excess morbidity and mortality from cardiovascular diseases later in life. Until now, reference values for the basic cardiovascular health characteristics of 4-to-6 year-old children are lacking. Within a follow-up study of the ENVIRONAGE (ENVIRonmental influence ON early AGE) birth cohort we assessed various cardiovascular measurements in 288 children aged 4-5 years. For the macrovasculature, we measured their blood pressure and examined the intima-media thickness of the carotid artery (CIMT), the arterial elasticity (including the pulse-wave velocity (PWV), carotid distensibility (DC) and compliance (CC) coefficients), the carotid beta stiffness index (SI beta) and Young's Elastic Modulus (YEM). Retinal microvascular traits included the Central Retinal Arteriolar Equivalent (CRAE) and Central Retinal Venular Equivalent (CRVE). Age of the study population averaged (+/- SD) 4.2 (+/- 0.4 years. Mean systolic and diastolic blood pressure were 97.9 (+/- 8.1) mmHg and 54.7(+/- 7.6) mmHg, respectively. CIMT for the total population averaged 487.1 (+/- 68.1) mu m. The average stiffness values for DC, CC, SI beta, and PWV were 78.7 (+/- 34.2) 10-(3)/kPa, 1.61 (+/- 0.59) mm(2)/kPa and 4.4 (+/- 2.4), and 3.7 m/s (+/- 0.9) respectively. The mean determined for YEM was 163.2 kPa (+/- 79.9). Concerning the microvasculature, the average CRAE was 180.9 (+/- 14.2) mu m and the corresponding value for CRVE was 251.0 (+/- 19.7) mu m. In contrast to the macrovasculature, a significant gender-related difference existed for the microvasculature: in boys, both the CRAE (178.8 mu m vs 182.6 mu m; p = 0.03) and CRVE (247.9 mu m vs 254.0 mu m; p = 0.01) were narrower than in girls. We have provided reference values for young children to understand changes in the early cardiovascular health trajectory. Establishing these reference values of cardiovascular phenotypes at this young age is necessary to develop targeted health promotion strategies as well as for better understanding of the life course changes of both small and large blood vessels