The relationship between weight change and inflammatory bowel disease. A population-based cohort study, the HUNT study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is increasing. The prevalence of overweight and obesity is increasing in parallel with IBD and could contribute to IBD development. The aim of this study was to assess the relationship between weight change and the risk for IBD. METHODS: Data gathered from 55,896 adult participants in the three first population-based Trøndelag Health Studies (HUNT1-3), Norway, performed in 1984-2008 was used. The exposure was change in body mass index between two HUNT studies. The outcome was a new IBD diagnosis recorded during a ten-year follow-up period after the exposure assessment. The risk of IBD by weight change was assessed by Cox regression analyses reporting hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for sex, age, and smoking status. RESULTS: There were 334 new cases of ulcerative colitis (UC) and 54 of Crohn's disease (CD). Weight loss decreased the risk of a new UC diagnosis by 38% (adjusted HR 0.62, 95% CI 0.39-0.97) and seemed to double the risk of getting a new CD diagnosis (adjusted HR 2.01, 95% CI 0.91-4.46). Weight gain was not associated with a new diagnosis of neither UC (adjusted HR 1.00, 95% CI 0.78-1.26) nor CD (adjusted HR 1.08, 95% CI 0.56-2.08). CONCLUSION: In this study, weight loss was associated with decreased risk of UC. However, no associations were seen between weight gain and the risk of UC or CD, suggesting that the increasing weight in the general population cannot explain the increasing incidence of IBD.

Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

Classification of Scalp EEG States Prior to Clinical Seizure Onset.

OBJECTIVE: To investigate the feasibility of improving the performance of an EEG-based multistate classifier (MSC) previously proposed by our group. RESULTS: Using the random forest (RF) classifiers on the previously reported dataset of patients, but with three improvements to classification logic, the specificity of our alarm algorithm improves from 82.4% to 92.0%, and sensitivity from 87.9% to 95.2%. DISCUSSION: The MSC could be a useful approach for seizure-monitoring both in the clinic and at home. METHODS: Three improvements to the MSC are described. Firstly, an additional check using RF outputs is made prior to alarm to confirm increasing probability of a seizure onset state. Secondly, a post-alarm detection horizon that accounts for the seizure state duration is implemented. Thirdly, the alarm decision window is kept constant.

Classification of Pre-Clinical Seizure States Using Scalp EEG Cross-Frequency Coupling Features.

OBJECTIVE: This work proposes a machine-learning based system for a scalp EEG that flags an alarm in advance of a clinical seizure onset. METHODS: EEG recordings from 12 patients with drug resistant epilepsy were marked by an expert neurologist for clinical seizure onset. Scalp EEG recordings consisted of 56 seizures and 9.67 h of interictal periods. Data from six patients were reserved for testing, and the rest was split into training and testing sets. A global spatial average of a cross-frequency coupling (CFC) index, , was extracted in 2 s windows, and used as the feature for the machine learning. A multistage state classifier (MSC) based on random forest algorithms was trained and tested on these data. Training was conducted to classify three states: interictal baseline, and segments prior to and following EG onset. Classifier performance was assessed using a receiver-operating characteristic (ROC) analysis. RESULTS: The MSC produced an alarm 45 16 s in advance of a clinical seizure onset across seizures from the 12 patients. It performed with a sensitivity of 87.9%, a specificity of 82.4%, and an area-under-the-ROC of 93.4%. On patients for whom it received training, performance metrics increased. Performance metrics did not change when the MSC used reduced electrode ring configurations. CONCLUSION: Using the scalp , the MSC produced an alarm in advance of a clinical seizure onset for all 12 patients. Patient-specific training improved the specificity of classification. SIGNIFICANCE: The MSC is noninvasive, and demonstrates that CFC features may be suitable for use in a home-based seizure monitoring system.

Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.

PURPOSE: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy. METHODS: This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion. RESULTS: Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048). CONCLUSIONS: Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.

An Overview of Psychogenic Non-Epileptic Seizures: Etiology, Diagnosis and Management.

The purpose of this review is to provide an update of the research regarding the etiology, diagnosis and management of psychogenic non-epileptic seizures (PNES). A literature search using Pubmed, Ovid MEDLINE and EMBASE database was performed from 2000 up to August 2017. We have evaluated the different factors leading to PNES as well as the diagnostic approach and management of this disorder which continue to be very difficult. The coexistence of epilepsy and PNES poses special challenges and requires the coordinated efforts of the family physicians, psychiatrists, psychologists and neurologists. Although this condition has an overall poor prognosis, a multidisciplinary approach in the diagnosis and management of this disorder would likely improve the outcomes. We have proposed a diagnostic and treatment algorithm for PNES and suggested a national registry of patients suffering from this condition. The registry would contain data regarding treatment and outcomes to aid in the understanding of this entity.

Mortality with brainstem seizures from focal 4-aminopyridine-induced recurrent hippocampal seizures.

OBJECTIVE: Sudden unexplained death in epilepsy is the leading cause of death in young adult epilepsy patients, typically occurring during the early postictal period, presumably resulting from brainstem and cardiorespiratory dysfunction. We hypothesized that ictal discharges in the brainstem disrupt the cardiorespiratory network, causing mortality. To study this hypothesis, we chose an animal model comprising focal unilateral hippocampal injection of 4-aminopyridine (4-AP), which produced focal recurrent hippocampal seizures with secondary generalization in awake, behaving rats. METHODS: We studied ictal and interictal intracranial electrographic activity (iEEG) in 23 rats implanted with a custom electrode array into the hippocampus, the contralateral cortex, and brainstem. The hippocampal electrodes contained a cannula to administer the potassium channel blocker and convulsant (4-AP). iEEG was recorded continuously before, during, and after seizures induced by 4-AP infusion into the hippocampus. RESULTS: The control group (n = 5) was monitored for 2-3 months, and the weekly baseline iEEG recordings showed long-term stability. The low-dose group (1 µL 4-AP, 40 mm, n = 5) exhibited local electrographic seizures without spread to the contralateral cerebral cortex or brainstem. The high-dose group (5 µL 4-AP, 40 mm, n = 3) had several hippocampal electrographic seizures, which spread contralaterally and triggered brainstem discharges within 40 min, and were associated with violent motor seizures followed by dyspnea and respiratory arrest, with cortical and hippocampal iEEG flattening. The group that received high-dose 4-AP without brainstem implantation (n = 5) had similar seizure-related respiratory difficulties. Finally, five rats that received high-dose 4-AP without EEG recording also developed violent motor seizures with postictal respiratory arrest. Following visualized respiratory arrest in groups III, IV, and V, manual respiratory resuscitation was successful in five of 13 animals. SIGNIFICANCE: These studies show that hippocampal seizure activity can spread or trigger brainstem epileptiform discharges that may cause mortality, possibly mediated by respiratory network dysfunction.

Epileptogenic Source Imaging Using Cross-Frequency Coupled Signals From Scalp EEG.

OBJECTIVE: The epileptogenic zone (EZ) is a brain region containing the sources of seizure genesis. Removal of the EZ is associated with cessation of seizures after resective surgical procedures, as measured by Engel Class I score. This study describes a novel EEG (electroencephalography) source imaging (ESI) method which uses cross-frequency coupled potential signals (SCFC) derived from scalp EEG. METHODS: Scalp EEG were recorded from ten patients (20 seizures) suffering from epilepsy. The S CFC were constructed from the phase and amplitude of the lower and higher frequency rhythms at electrographic seizure onset. ESI was then performed using the SCFC. Validation of the technique was facilitated by forward and inverse computer modeling of known cortical sources, and the correspondence of the ESI with EZ in resected regions of patients. RESULTS: For ten seizures sampled at or above 500 Hz from four patients, all estimated sources lay within the resected region, emphasizing the clinical importance of higher sampling rates. The SCFC demonstrated significant advantages over the "raw" scalp EEG, indicating its robust noise performance. Modeling investigations indicated that a signal-to-noise ratio above 0.2 was sufficient to achieve successful localization regarding EMG artifacts. CONCLUSION: The association of the estimated sources to the EZ suggests that cross-frequency coupling is a feature of the brain's neural networks, not of artifactual activity. The SCFC can effectively extract brain signals from a noisy background. SIGNIFICANCE: We propose this approach to enhance the placement of intracranial electrode for surgical intervention.

Spatial Coherence Profiles of Ictal High-Frequency Oscillations Correspond to Those of Interictal Low-Frequency Oscillations in the ECoG of Epileptic Patients.

GOAL: We have previously demonstrated that the coherence of high-frequency oscillations (HFOs; 80-300 Hz) increased during extratemporal lobe seizures in a consistent and spatially focused electrode cluster. In this study, we have investigated the relationship between cohered HFO intracranial EEG (iEEG) activity with that of slower low-frequency oscillations (LFOs; <80 Hz). METHODS: We applied wavelet phase coherence analysis to the iEEGs of patients with intractable extratemporal lobe epilepsy (ETLE). RESULTS: It was observed that areas on the implanted patient subdural grids, which exhibited strong ictal HFO coherence were similar to tissue regions displaying strong interictal LFO coherence in the 5-12 Hz frequency range, relative to all other electrodes. A positive surgical outcome was correlated with having the clinically marked seizure onset zone(s) in close proximity to HFO/LFO coherence highlighted regions of interest (ROIs). CONCLUSION: Recent studies have suggested that LFOs (in the 8-12 Hz frequency range) play an important role in controlling cortical excitability, by exerting an inhibitory effect on cortical processing, and that the presence of strong theta activity (4-8 Hz) in awake adults is suggestive of abnormal and/or pathological activity. We speculate that the overlapping spatial regions exhibiting increased coherence in both ictal HFOs and interictal LFOs identified local abnormalities that underlie epileptogenic networks. SIGNIFICANCE: Whereas it is worthwhile to note that the small patient group ( n = 7) studied here, somewhat limits the clinical significance of our study, the results presented here suggest targeting HFO activity in the 80-300 Hz frequency range and/or interictal LFO activity in the 5-12 Hz frequency range, when defining seizure-related ROIs in the iEEGs of patients with ETLE.

Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients.

OBJECTIVE: Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs). METHODS: Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase-amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5-4 Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed. MAIN RESULTS: MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected tissue suggesting that the resected tissue was not appropriate, which was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel Class I patient. SIGNIFICANCE: LFO-modulated HFOs can be used to identify ROIs in extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more accurate localization of the EZ. These ROIs may result in better surgical outcomes when used to compliment the SOZs identified by clinicians for resection.

Mapping the coherence of ictal high frequency oscillations in human extratemporal lobe epilepsy.

OBJECTIVE: High frequency oscillations (HFOs) have recently been recorded in epilepsy patients and proposed as possible novel biomarkers of epileptogenicity. Investigation of additional HFO characteristics that correlate with the clinical manifestation of seizures may yield additional insights for delineating epileptogenic regions. To that end, this study examined the spatiotemporal coherence patterns of HFOs (80-400 Hz) so as to characterize the strength of HFO interactions in the epileptic brain. We hypothesized that regions of strong HFO coherence identified epileptogenic networks believed to possess a pathologic locking nature in relation to regular brain activity. METHODS: We applied wavelet phase coherence analysis to the intracranial EEG (iEEG)s of patients (n = 5) undergoing presurgical evaluation of drug-resistant extratemporal lobe epilepsy (ETLE). We have also computed HFO intensity (related to the square-root of the power), to study the relationship between HFO amplitude and coherence. RESULTS: Strong HFO (80-270 Hz) coherence was observed in a consistent and spatially focused channel cluster during seizures in four of five patients. Furthermore, cortical regions possessing strong ictal HFO coherence coincided with regions exhibiting high ictal HFO intensity, relative to all other channels. SIGNIFICANCE: Because HFOs have been shown to localize to the epileptogenic zone, and we have demonstrated a correlation between ictal HFO intensity and coherence, we propose that ictal HFO coherence can act as an epilepsy biomarker. Moreover, the seizures studied here showed strong spatial correlation of ictal HFO coherence and intensity in the 80-270 Hz frequency range, suggesting that this band may be targeted when defining seizure-related regions of interest for characterizing ETLE.

An approach to the histomorphological and histochemical variations of the humerus cortical bone through human ontogeny.

For many years, clinical and non-clinical investigations have investigated cortical bone structure in an attempt to address questions related to normal bone development, mineralisation, pathologies and even evolutionary trends in our lineage (adaptations). Research in the fields of medicine, materials science, physical anthropology, palaeontology, and even archaeobiology has contributed interesting data. However, many questions remain regarding the histomorphological and histochemical variations in human cortical bone during different stages of life. In the present work, we describe a study of long bone cortex transformations during ontogeny. We analysed cross-sections of 15 human humeri histomorphologically and histochemically from perinatal to adult age, marking and quantifying the spatial distribution of bone tissue types using GIS software and analysing the mineral composition and crystallinity of the mineralised cortex using Raman spectroscopy and X-ray diffraction. Our results allowed us to propose that human cortical bone undergoes three main 'events' through ontogeny that critically change the proportions and structure of the cortex. In early development, bone is not well mineralised and proportionally presents a wide cortex that narrows through the end of childhood. Before reaching complete maturity, the bone mineral area increases, allowing the bone to nearly reach the adult size. The medullary cavity is reduced, and the mineral areas have a highly ordered crystalline structure. The last event occurs in adulthood, when the 'oldest' individuals present a reduced mineralised area, with increasing non-mineralised cavities (including the medullary cavity) and reduced crystalline organisation.

Early loosening of a press-fit cup with ceramic-on-ceramic articulation: our early results.

INTRODUCTION: In this study, we present the short-term results of the Selexys TH+ cup with the Ceramys inlay which is a press-fit cup with a ceramic-on-ceramic articulation. (Mathys, Bettlach, Switzerland). We compared the results with a retrospective-matched control group with a Delta PF cup (Lima, Udine, Italy), which is also a press-fit cup with a ceramic-on-ceramic articulation. MATERIALS AND METHODS: 257 elective hip arthroplasties with the Selexys TH+ cup in 250 patients placed in 2009 and 2010 were analyzed and compared with a control group retrospective analysis of the uncemented Delta PF cup (Lima, Udine, Italy) placed in 2007 and 2008 in 208 patients (222 hips). Surgical technique and surgeons were identical in both groups. RESULTS: During a follow-up period of 3-21 months, 19 aseptic loosenings (7.4 %) were found for the Selexys TH+ cup. The survival plotted by a Kaplan-Meier curve shows a 1-year survival of 87.4 %. The Lima Delta PF cup showed a 1-year survival of 99.5 %. Failure analysis showed no clear explanation for this early loosening. CONCLUSION: The Selexys TH+ cup combined with the Ceramys ceramic-on-ceramic inlay coupling show an unacceptable high early revision rate. Therefore, we advice against using this combination.

Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14-16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM) than in CON rodents (6.3 ± 0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM) and CON animals (1.6 ± 0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.

Mapping human long bone compartmentalisation during ontogeny: a new methodological approach.

Throughout ontogeny, human bones undergo differentiation in terms of shape, size and tissue type; this is a complex scenario in which the variations in the tissue compartmentalisation of the cortical bone are still poorly understood. Currently, compartmentalisation is studied using methodologies that oversimplify the bone tissue complexity. Here, we present a new methodological approach that integrates a histological description and a mineral content analysis to study the compartmentalisation of the whole mineralised and non-mineralised tissues (i.e., spatial distribution in long bone sections). This new methodology, based on Geographical Information System (GIS) software, allows us to draw areas of interest (i.e., tracing vectorial shapes which are quantifiable) in raw images that are extracted from microscope and compared them spatially in a semi-automatic and quantitative fashion. As an example of our methodology, we have studied the tibiae from individuals with different age at death (infant, juvenile and adult). The tibia's cortical bone presents a well-formed fibrolamellar bone, in which remodelling is clearly evidenced from early ontogeny, and we discuss the existence of "lines of arrested growth". Concurrent with the histological variation, Raman and FT-IR spectroscopy analyses corroborate that the mineral content in the cortical bone changes differentially. The anterior portion of the tibia remains highly pierced and is less crystalline than the rest of the cortex during growth, which is evidence of more active and continuous remodelling. Finally, while porosity and other "non-mineralised cavities" are largely modified, the mineralised portion and the marrow cavity size persist proportionally during ontogeny.

Above- or below-elbow casts for distal third forearm fractures in children? A meta-analysis of the literature.

INTRODUCTION: Fractures of the distal third forearm are common fractures in childhood. Most of these fractures can be treated non-operatively by means of closed reduction and immobilization. The purpose of this meta-analysis is to investigate whether above- or below-elbow cast should be considered the first-choice for conservative treatment. MATERIALS AND METHODS: A search was performed in multiple databases to identify all the studies comparing above- and below-elbow cast for the treatment of distal third forearm fractures in children. All RCT's or CCT's were assessed for eligibility. Quality was assessed by the Cochrane Musculoskeletal Injuries Group assessment. Data were pooled using RevMan 5.0 RESULTS: Three trials involving a total of 300 participants were included. A total of 142 fractures were treated with a below-elbow cast (BEC) versus 158 with an above-elbow cast (AEC). Loss of reduction was encountered in 17 and 36 cases, respectively [odds ratio 0.44 (0.22-0.87)]. For combined radius and ulna fractures 15 of 97 in the BEC group and 34 out of 122 in the AEC group showed loss of reduction [odds ratio 0.55 (0.26-1.15)]. Children treated with BEC missed less school days [mean difference 1.12 (-1.52 to -0.59)], and encountered less difficulties in daily living [odds ratio 112.41 (6.58-1920.77)]. CONCLUSION: Due to heterogeneity, the trials are not fully compared. Based on the presented meta-analysis, we conclude that BEC is not inferior to AEC so that this is a valid treatment option for distal third forearm fractures.