Marco Carone

Progressive Multifocal Leukoencephalopathy in Transplant Recipients

Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), a rare demyelinating disorder caused by oligodendrocyte destruction by JC virus.

Second-opinion consultations in neuroradiology.

PURPOSE To assess the patient care benefit of a recently implemented institutional policy requiring official second-opinion consultation for all studies performed outside the institution. MATERIALS AND METHODS The institutional review board approved the retrospective review of patient data for this HIPAA-compliant study and waived the need for individual informed consent. The second-opinion consultation reports for outside neuroradiology studies finalized by subspecialty-trained neuroradiologists within calendar year 2008 were compared with the outside reports provided with the images. The reports were categorized by using a five-point scale: 1 indicated no difference in interpretation; 2, clinically unimportant difference in detection; 3, clinically unimportant difference in interpretation; 4, clinically important difference in detection; and 5, clinically important difference in interpretation. Clinically important differences were defined as those likely to change patient care or diagnoses. Statistical comparisons were performed by using two-sample continuity-corrected Z tests with two-sided alternatives. Bonferroni corrections were performed when more than two rates were compared. Confidence intervals for all rates were constructed by using the score interval along with the Yates continuity correction. RESULTS Of 7465 studies, 4534 (60.7%) had an outside report for comparison. There were 347 (7.7%) instances with clinically important differences. Of these 347 discrepancies, 233 (67.1%) were category 4 and 114 (32.9%) were category 5. When the final diagnosis was determined from pathology reports, clinical assessments, and/or imaging follow-up, the second-opinion consultation was noted to be correct in 163 (84.0%) of 194 studies with category 4 or 5 discrepancies. CONCLUSION A 7.7% rate of discrepant interpretations (347 of 4534 studies) was noted for a service offering second-opinion consultations for outside examinations. Most were discrepancies in detecting abnormalities rather than in interpreting identified findings. When a definitive diagnosis was obtainable, the second-opinion consultation was more accurate in 84% of studies. Review of outside studies benefits patient care.

Long-term cognitive outcomes following out-of-hospital cardiac arrest A population-based study

Objective: To report the neurologic outcomes in long-term survivors of out-of-hospital cardiac arrest with ventricular fibrillation as the presenting rhythm (OHCA VF) at a population level. Methods: All adults who experienced OHCA VF in Olmsted County, MN, from 1990 to 2008, survived more than 6 months postarrest, and were alive at the time of study recruitment were invited to participate in structured neuropsychological testing and a neurologic examination. Cognitive test results were compared to the normal population using the Mayos Older Adults Normative Studies. Linear regression models were fit to evaluate each neuropsychological test result in relation to call-to-shock time, sex, age at cardiac arrest, time elapsed since event, witnessed vs unwitnessed arrest, and administration of bystander cardiopulmonary resuscitation. Results: Of 332 OHCA VF arrests, 140 people (42.2%, 95% confidence interval 36.9%–47.5%) survived to discharge. No patient entered a minimally conscious or permanent vegetative state. Long-term survivors (n = 47, median survival 7.8 years postarrest) had lower scores on measures of long-term memory and learning efficiency (p = 0.001) but higher than average scores on verbal IQ (p = 0.001). Nearly all survivors were functionally independent and scored high on the Mini-Mental State Examination (MMSE) (median Barthel Index 100/100, median MMSE 29/30). Conclusions: Long-term survivors of OHCA VF have long-term memory deficits compared to the normal population at the same age and education level. These findings provide a baseline for cognitive outcomes studies of OHCA VF as new techniques are developed to improve survival.

Mortality prediction in intensive care units with the Super ICU Learner Algorithm (SICULA): a population-based study

BACKGROUND Improved mortality prediction for patients in intensive care units is a big challenge. Many severity scores have been proposed, but findings of validation studies have shown that they are not adequately calibrated. The Super ICU Learner Algorithm (SICULA), an ensemble machine learning technique that uses multiple learning algorithms to obtain better prediction performance, does at least as well as the best member of its library. We aimed to assess whether the Super Learner could provide a new mortality prediction algorithm for patients in intensive care units, and to assess its performance compared with other scoring systems. METHODS From January, 2001, to December, 2008, we used the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database (version 26) including all patients admitted to an intensive care unit at the Beth Israel Deaconess Medical Centre, Boston, MA, USA. We assessed the calibration, discrimination, and risk classification of predicted hospital mortality based on Super Learner compared with SAPS-II, APACHE-II, and SOFA. We calculated performance measures with cross-validation to avoid making biased assessments. Our proposed score was then externally validated on a dataset of 200 randomly selected patients admitted at the intensive care unit of Hôpital Européen Georges-Pompidou, Paris, France, between Sept 1, 2013, and June, 30, 2014. The primary outcome was hospital mortality. The explanatory variables were the same as those included in the SAPS II score. FINDINGS 24,508 patients were included, with median SAPS-II of 38 (IQR 27-51) and median SOFA of 5 (IQR 2-8). 3002 of 24,508 (12%) patients died in the Beth Israel Deaconess Medical Centre. We produced two sets of predictions based on the Super Learner; the first based on the 17 variables as they appear in the SAPS-II score (SL1), and the second, on the original, untransformed variables (SL2). The two versions yielded average predicted probabilities of death of 0·12 (IQR 0·02-0·16) and 0·13 (0·01-0·19), whereas the corresponding value for SOFA was 0·12 (0·05-0·15) and for SAPS-II 0·30 (0·08-0·48). The cross-validated area under the receiver operating characteristic curve (AUROC) for SAPS-II was 0·78 (95% CI 0·77-0·78) and 0·71 (0·70-0·72) for SOFA. Super Learner had an AUROC of 0·85 (0·84-0·85) when the explanatory variables were categorised as in SAPS-II, and of 0·88 (0·87-0·89) when the same explanatory variables were included without any transformation. Additionally, Super Learner showed better calibration properties than previous score systems. On the external validation dataset, the AUROC was 0·94 (0·90-0·98) and calibration properties were good. INTERPRETATION Compared with conventional severity scores, Super Learner offers improved performance for predicting hospital mortality in patients in intensive care units. A user-friendly implementation is available online and should be useful for clinicians seeking to validate our score. FUNDING Fulbright Foundation, Assistance Publique-Hôpitaux de Paris, Doris Duke Clinical Scientist Development Award, and the NIH.

Neurologic disorders incidence in HIV+ vs HIV− men Multicenter AIDS Cohort Study, 1996–2011

Objective: To study the incidence and pattern of neurologic disorders in a large cohort of HIV-positive men, compared with HIV-negative men, in the era of highly active antiretroviral therapy (HAART). Methods: The Multicenter AIDS Cohort Study is a prospective study of men who have sex with men enrolled in 4 cities in the United States. We compared HIV-positive vs HIV-negative men for incidence and category of neurologic diagnoses in the HAART era (July 1, 1996, to last known follow-up or death, on or before July 1, 2011). Results: There were 3,945 participants alive during the HAART era (2,083 HIV negative, 1,776 HIV positive, and 86 who became infected with HIV during the study period) including 3,427 who were older than 40 years of age. Median age at first neurologic diagnosis among all participants alive in the HAART era was lower in HAART-treated HIV-positive vs HIV-negative men (48 vs 57 years of age, p < 0.001). Incidence of neurologic diagnoses was higher in HAART-treated HIV-positive vs HIV-negative men (younger than 40 years: 11.4 vs 0 diagnoses per 1,000 person-years [p < 0.001]; 40–49 years: 11.6 vs 2.0 [p < 0.001]; 50–60 years: 15.1 vs 3.0 [p < 0.001]; older than 60 years: 17.0 vs 5.7 [p < 0.01]). Excess neurologic disease was found in the categories of nervous system infections (p < 0.001), dementia (p < 0.001), seizures/epilepsy (p < 0.01), and peripheral nervous system disorders (p < 0.001), but not stroke (p = 0.60). Conclusions: HIV-positive men receiving HAART have a higher burden of neurologic disease than HIV-negative men and develop neurologic disease at younger ages.

Brain death declaration: Practices and perceptions worldwide.

Objective: To assess the practices and perceptions of brain death determination worldwide and analyze the extent and nature of variations among countries. Methods: An electronic survey was distributed globally to physicians with expertise in neurocritical care, neurology, or related disciplines who would encounter patients at risk of brain death. Results: Most countries (n = 91, response rate 76%) reported a legal provision (n = 63, 70%) and an institutional protocol (n = 70, 77%) for brain death. Institutional protocols were less common in lower-income countries (2/9 of low [22%], 9/18 lower-middle [50%], 22/26 upper-middle [85%], and 37/38 high-income countries [97%], p < 0.001). Countries with an organized transplant network were more likely to have a brain death provision compared with countries without one (53/64 [83%] vs 6/25 [24%], p < 0.001). Among institutions with a formalized brain death protocol, marked variability occurred in requisite examination findings (n = 37, 53% of respondents deviated from the American Academy of Neurology criteria), apnea testing, necessity and type of ancillary testing (most commonly required test: EEG [n = 37, 53%]), time to declaration, number and qualifications of physicians present, and criteria in children (distinct pediatric criteria: n = 38, 56%). Conclusions: Substantial differences in perceptions and practices of brain death exist worldwide. The identification of discrepancies, improvement of gaps in medical education, and formalization of protocols in lower-income countries provide first pragmatic steps to reconciling these variations. Whether a harmonized, uniform standard for brain death worldwide can be achieved remains questionable.

Imaging Characteristics of Oligodendrogliomas That Predict Grade

BACKGROUND AND PURPOSE: Oligodendrogliomas are tumors that have variable WHO grades depending on anaplasia and astrocytic components and their treatment may differ accordingly. Our aim was to retrospectively evaluate imaging features of oligodendrogliomas that predict tumor grade. MATERIALS AND METHODS: The imaging studies of 75 patients with oligodendrogliomas were retrospectively reviewed and compared with the histologic grade. The presence and degree of enhancement and calcification were evaluated subjectively. rCBV and ADC maps were measured. Logistic linear regression models were used to determine the relationship between imaging factors and tumor grade. RESULTS: Thirty of 75 (40%) tumors enhanced, including 9 of 46 (19.6%) grade II and 21 of 29 (72.4%) grade III tumors (P < .001). Grade III tumors showed lower ADC values compared with grade II tumors (odds ratio of a tumor being grade III rather than grade II = 0.07; 95% CI, 0.02–0.25; P = .001). An optimal ADC cutoff of 925 10−6 mm2/s was established, which yielded a specificity of 89.1%, sensitivity of 62.1%, and accuracy of 78.7%. There was no statistically significant association between tumor grade and the presence of calcification and perfusion values. Multivariable prediction rules were applied for ADC < 925 10−6 mm2/s, the presence of enhancement, and the presence of calcification. If either ADC < 925 10−6 mm2/s or enhancement was present, it yielded 93.1% sensitivity, 73.9% specificity, and 81.3% accuracy. The most accurate (82.2%) predictive rule was seen when either ADC < 925 10−6 mm2/s or enhancement and calcification were present. CONCLUSIONS: Models based on contrast enhancement, calcification, and ADC values can assist in predicting the grade of oligodendrogliomas and help direct biopsy sites, raise suspicion of sampling error, and predict prognosis.

A population-based case-control study of 1250 stroke deaths in rural Bangladesh.

Background and purpose: There are limited population‐based studies to determine the risk factors for stroke in Bangladesh.

Increased birth weight associated with regular pre-pregnancy deworming and weekly iron-folic acid supplementation for Vietnamese women.

Background Hookworm infections are significant public health issues in South-East Asia. In women of reproductive age, chronic hookworm infections cause iron deficiency anaemia, which, upon pregnancy, can lead to intrauterine growth restriction and low birth weight. Low birth weight is an important risk factor for neonatal and infant mortality and morbidity. Methodology We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam. The program was made available to all women of reproductive age (estimated 51,623) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection. Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention, but had similar maternal and child health indicators and socio-economic backgrounds. The primary outcome was low birth weight. Principal Findings The birth weights of 463 infants born in district hospitals in the intervention (168) and control districts (295) were recorded. Twenty-six months after the program was started, the prevalence of low birth weight was 3% in intervention districts compared to 7.4% in control districts (adjusted odds ratio 0.29, 95% confidence interval 0.10 to 0.81, p = 0.017). The mean birth weight was 124 g (CI 68 - 255 g, p<0.001) greater in the intervention districts compared to control districts. Conclusions/Significance The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam. The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive randomised-controlled trial.

Medical conditions among Iraqi refugees in Jordan: data from the United Nations Refugee Assistance Information System

OBJECTIVE To determine the range and burden of health services utilization among Iraqi refugees receiving health assistance in Jordan, a country of first asylum. METHODS Medical conditions, diagnosed in accordance with the tenth revision of the International classification of diseases, were actively monitored from 1 January to 31 December 2010 using a pilot centralized database in Jordan called the Refugee Assistance Information System. FINDINGS There were 27 166 medical visits by 7642 Iraqi refugees (mean age: 37.4 years; 49% male; 70% from Baghdad; 6% disabled; 3% with a history of torture). Chronic diseases were common, including essential hypertension (22% of refugees), visual disturbances (12%), joint disorders (11%) and type II diabetes mellitus (11%). The most common reasons for seeking acute care were upper respiratory tract infection (11%), supervision of normal pregnancy (4%) and urinary disorders (3%). The conditions requiring the highest number of visits per refugee were cerebrovascular disease (1.46 visits), senile cataract (1.46) and glaucoma (1.44). Sponsored care included 31 747 referrals or consultations to a specialty service, 18 432 drug dispensations, 2307 laboratory studies and 1090 X-rays. The specialties most commonly required were ophthalmology, dentistry, gynaecology and orthopaedic surgery. CONCLUSION Iraqi refugees in countries of first asylum and resettlement require targeted health services, health education and sustainable prevention and control strategies for predominantly chronic diseases.