MRI based preterm white matter injury classification: the importance of sequential imaging in determining severity of injury

The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings.Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI.138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami.In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI

Environmental influences on energy balance-related behaviors: A dual-process view

BACKGROUND: Studies on the impact of the 'obesogenic' environment have often used non-theoretical approaches. In this journal's debate and in other papers authors have argued the necessity of formulating conceptual models for differentiating the causal role of environmental influences on behavior. DISCUSSION: The present paper aims to contribute to the debate by presenting a dual-process view on the environment – behavior relationship. This view is conceptualized in the EnRG framework (Environmental Research framework for weight Gain prevention). In the framework, behavior is postulated to be the result of a simultaneous influence of conscious and unconscious processes. Environmental influences are hypothesized to influence behavior both indirectly and directly. The indirect causal mechanism reflects the mediating role of behavior-specific cognitions in the influence of the environment on behavior. A direct influence reflects the automatic, unconscious, influence of the environment on behavior. Specific personal and behavioral factors are postulated to moderate the causal path (i.e., inducing either the automatic or the cognitively mediated environment – behavior relation). In addition, the EnRG framework applies an energy balance-approach, stimulating the integrated study of determinants of diet and physical activity. CONCLUSION: The application of a dual-process view may guide research towards causal mechanisms linking specific environmental features with energy balance-related behaviors in distinct populations. The present paper is hoped to contribute to the evolution of a paradigm that may help to disentangle the role of 'obesogenic' environmental factors

Peer support to decrease diabetes-related distress in patients with type 2 diabetes mellitus:Design of a randomised controlled trial

BACKGROUND: Many type 2 diabetes mellitus patients face difficulties self-managing their illness, which can lead to high levels of diabetes-related distress. Diabetes distress may be decreased by peer support, as peers understand and have dealt with similar problems, and can help motivate each other. A recent systematic review concluded that evidence of benefits of peer support in patients with type 2 diabetes mellitus is too inconsistent due to weak theoretical foundation of the interventions. This study describes the design of a trial evaluating the effectiveness of a group-based, peer support programme with a strong theoretical foundation on diabetes-related distress in type 2 diabetes patients. METHODS: This is a parallel group randomised controlled trial of a six session group-based peer support intervention, delivered by peer leaders and group psychotherapists, compared with one educational meeting on diabetes. At least 152 patients with a type 2 diabetes duration of three years or more and between 50 and 70 years of age, recruited via their general practitioner, will be randomised to receive the peer support intervention or one educational meeting. The intervention is developed in line with three key stages of research development of the Medical Research Council framework. The primary outcome measure for this study is diabetes-related distress. Secondary outcomes include self-management behaviour, well-being and health-related quality of life. Perceived social support is a process measure. Outcomes will be measured one month before, and 6, and 12 months after the intervention by means of self-reported questionnaires. Analysis will be on an intention-to-treat basis. DISCUSSION: This article contains a description of the design of a study that will investigate the effect of a group-based, peer support intervention on diabetes-related distress in type 2 diabetes patients. The intervention was developed in recognition of the limited evidence, and the importance of a theoretical foundation and its implementation. Findings will contribute to knowledge in the field of peer support and patient-important outcomes in type 2 diabetes patients. TRIAL REGISTRATION: Dutch Trial Registry: NTR347

Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia

OBJECTIVE: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia. METHODS: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome. RESULTS: EEG background activity was significantly associated with neurodevelopmental outcome at 36 h (p = 0.009) and 48 h after birth (p = 0.029) and with severity of brain injury on MRI at 36 h (p = 0.002) and 48 h (p = 0.018). All infants with a high seizure burden and moderate-severe injury on MRI had an abnormal outcome. The positive predictive value (PPV) of EEG for abnormal outcome was 100% at 36 h and 48 h and the negative predictive value (NPV) was 75% at 36 h and 69% at 48 h. The PPV of MRI was 100% and the NPV 85%. The PPV of seizure burden was 78% and the NPV 71%. CONCLUSION: Severely abnormal EEG background activity at 36 h and 48 h after birth was associated with severe injury on MRI and abnormal neurodevelopmental outcome. High seizure burden was only associated with abnormal outcome in combination with moderate-severe injury on MRI

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies

Background: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. / Methods: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36+0 weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy. / Findings: Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3–28] vs 68 h [35–86], p<0·0001), more seizures (median 12 [IQR 5–36] vs 94 [24–134], p<0·0001), and higher total seizure burden (median 69 min [IQR 22–104] vs 167 min [54–275], p=0·0033). Hourly seizure burden peaked at about 20–24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7·09 [95% CI 1·88–26·77], p=0·0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5·64 [1·81–17·60], p=0·0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0·020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1·007 [95% CI 1·000–1·014], p=0·046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (rS=–0·477, p=0·014, n=26). / Interpretation: Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected. / Funding: Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board

Outcome in hip fracture patients related to anemia at admission and allogeneic blood transfusion: an analysis of 1262 surgically treated patients

Background: Anemia is more often seen in older patients. As the mean age of hip fracture patients is rising, anemia is common in this population. Allogeneic blood transfusion (ABT) and anemia have been pointed out as possible risk factors for poorer outcome in hip fracture patients. Methods. In the timeframe 2005-2010, 1262 admissions for surgical treatment of a hip fracture in patients aged 65 years and older were recorded. Registration was prospective from 2008 on. Anemic and non-anemic patients (based on hemoglobin level at admission) were compared regarding clinical characteristics, mortality, delirium incidence, LOS, discharge to a nursing home and the 90-day readmission rate. Receiving an ABT, age, gender, ASA classification, type of fracture and anesthesia were used as possible confounders in multivariable regression analysis. Results: The prevalence of anemia and the rate of ABT both were 42.5%. Anemic patients were more likely to be older and men and had more often a trochanteric fracture, a higher ASA score and received more often an ABT. In univariate analysis, the 3- and 12-month mortality rate, delirium incidence and discharge to a nursing home rate were significantly worse in preoperatively anemic patients. In multivariable regression analysis, anemia at admission was a significant risk factor for discharge to a nursing home and readmission < 90 days, but not for mortality. Indication for ABT, age and ASA classification were independent risk factors for mortality at all moments, only the mortality rate for the 3-12 month interval was not influenced by ABT. An indication for an ABT was the largest negative contributor to a longer LOS (OR 2.26, 95% CI 1.73-2.94) and the second largest for delirium (OR 1.67, 95% CI 1.28-2.20). Conclusions: This study has demonstrated that anemia at admission and postoperative anemia needing an ABT (PANT) were independent risk factors for worse outcome in hip fracture patients. In multivariable regression analysis, anemia as such had no effect on mortality, due to a rescue effect of PANT. In-hospital, 3- and 12-month mortality was negatively affected by PANT, with the main effect in the first 3 months postoperatively

The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

Neonatal Seizure Management – Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden; secondary aim was to describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks' gestation) requiring electroencephalographic (EEG) monitoring recruited to two multicentre European studies were included. Infants who received anti-seizure medication exclusively after electrographic seizure onset, were grouped based on time to treatment of the first seizure: ASM within 1-hour, ASM between 1-2 hours and ASM after 2-hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures and ASM dose over 24-hours following seizure onset. RESULTS: Out of 472 newborns recruited, 154(32.6%) infants had confirmed electrographic seizures. Sixty-nine infants were exclusively treated after onset of electrographic seizures: 21 infants received ASM within 1 hour, 15 infants between 1-2 hours and 33 infants after 2 hours of seizure onset. Significantly lower seizure burden and less seizures were noted in infants treated with ASM within 1 hour from seizure onset (p value=0.029 and 0.035, respectively). Overall, 258/472(54.7%) infants received ASM throughout the study period, of which 40 infants without electrographic seizures had treatment during EEG monitoring and 11 infants with electrographic seizures had no treatment. CONCLUSION: Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment

Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy

Aim: To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic–ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. Method: Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months–7 years 7 months] and 7 years 4 months [6 years 7 months–7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography. Results: More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. Interpretation: Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls