Background: Evidence for effective interventions to prevent long-term sequelae after concussion is sparse. This study aimed to test the efficacy of Get going After concussIoN (GAIN), an interdisciplinary, individuallytailored intervention of 8 weeks duration based on gradual return to activities and principles from cognitive behavioural therapy. Methods: We conducted an open-label, parallel-group randomised trial in a hospital setting in Central Denmark Region. Participants were 15À30-year-old patients with high levels of post-concussion symptoms (PCS) 2À6 months post-concussion (i.e., a score 20 on the Rivermead Post-concussion Symptoms Questionnaire (RPQ)). They were randomly assigned (1:1) to either enhanced usual care (EUC) or GAIN+EUC. Masking of participants and therapists was not possible. The primary outcome was change in RPQ-score from baseline to 3-month FU. All analyses were done on an intention-to-treat basis using linear mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT02337101. Findings: Between March 1, 2015, and September 1, 2017, we included 112 patients. Patients allocated to GAIN+EUC (n=57) reported a significantly larger reduction of PCS than patients allocated to EUC (n=55) with a mean adjusted difference in improvement of 7¢6 points (95% confidence interval (CI) 2¢0À13¢1, p=0¢008), Cohen's d=0¢5 (95% CI 0¢1À0¢9). Number needed to treat for prevention of one additional patient with RPQ 20 at 3-month FU was 3¢6 (95% CI 2¢2À11¢3). No adverse events were observed. Interpretation: Compared with EUC, GAIN+EUC was associated with a larger reduction of post-concussion symptoms at 3-month FU. Funding: Central Denmark Region and the foundation "Public Health in Central Denmark Region-a collaboration between municipalities and the region".
The new early intervention is feasible and may prevent chronification of PCS. An RCT is currently performed to evaluate the effect of the intervention.
Characteristics of persistent post-traumatic headache (PTH) in young individuals are poorly known leading to diagnostic problems and diverse management. We aimed to describe headache phenotypes and self-reported management strategies in young individuals with PTH following mild traumatic brain injury (mTBI). A comprehensive structured questionnaire was used to evaluate headache phenotypes/characteristics and management strategies to relieve headache in 107, 15–30-year-old individuals with PTH. Around 4 months post-injury, migraine-like headache in combination with tension-type like headache (40%) was the most commonly encountered headache phenotype followed by migraine-like headache (36%). Around 50% reported aura-like symptoms before/during the headache attack. Medication-overuse headache was diagnosed in 10%. Stress, sleep disturbances, and bright lights were the most common trigger factors. More than 80% reported that their headache was worsened by work-related activity and alleviated by rest/lying down. Simple analgesics were commonly used (88%) whereas prophylactic drugs were rarely used (5%). Bedrest and physiotherapy were also commonly used as management strategies by 56% and 34% of the participants, respectively. In conclusion, most young individuals with PTH after mTBI presented with combined migraine-like and tension-type-like headache followed by migraine-like headache, only. Preventive headache medication was rarely used, while simple analgesics and bedrest were commonly used for short-term headache relief.
Rearrangements affecting the MLL gene in hematological malignancies are associated with poor prognosis. Most often they are reciprocal translocations and more rarely complex forms involving at least 3 chromosomes. We describe an unusual case with cutaneous leukemic infiltrates that waxed and waned until progression to acute myeloid leukemia, AML-M5. The leukemic cells harbored a novel apparent 3-way translocation t(6;19;11)(p22.2;p13.1;q23.3). We utilized advanced molecular cytogenetic methods including 24-color karyotyping, high-resolution array comparative genomic hybridization (aCGH) and DNA sequencing to characterize the genomic complement in the leukemic cells from aspirated bone marrow cells at AML diagnosis. Karyotyping showed 47,XY,t(6;19;11)(p22;p13;q23),+der(6)t(6;11)(p22;q23)[17]/48,sl,+8[3]/48,sl,+8,der(12)t(1;12)(q11;p13)[3]/ 48,sdl,der(Y)t(Y;1)(q12;q11),+8[7] conferring MLL-ELL fusion. Oligo-aCGH analysis confirmed gains of 6p22qter and 11q23.3qter involving the CMAHP and MLL genes, respectively. DNA sequencing disclosed an additional breakpoint at 6p24.3 (at RREB1 gene). Retrospective fluorescence in situ hybridization revealed presence of the MLL-involving rearrangement in the initial stages of disease before clear morphological signs of bone marrow involvement. The patient responded well to therapy and remains in remission >6 years from diagnosis. This apparent 3-way translocation is remarkable because of its rarity and presentation with myeloid sarcoma, and may, as more cases are characterized, further our understanding onto how such complex translocations contribute to promote leukemogenesis and respond to therapy.
A recent randomized controlled trial in young patients with long-term post-concussion symptoms showed that a novel behavioral intervention "Get going After con-cussIoN" is superior to enhanced usual care in terms of symptom reduction. It is unknown whether these interventional effects are associated with microstructural brain changes. The aim of this study was to examine whether diffusion-weighted MRI indices, which are sensitive to the interactions between cellular structures and water molecules' Brownian motion, respond differently to the interventions of the above-mentioned trial and whether such differences correlate with the improvement of post-concussion symptoms. Twenty-three patients from the intervention group (mean age 22.8, 18 females) and 19 patients from the control group (enhanced usual care) (mean age 23.9, 14 females) were enrolled. The primary outcome measure was the mean kurtosis tensor, which is sensitive to the microscopic complexity of brain tissue. The mean kurtosis tensor was significantly increased in the intervention group (p = 0.003) in the corpus callosum but not in the thalamus (p = 0.78) and the hippocampus (p = 0.34). An increase in mean kurtosis tensor in the corpus callosum tended to be associated with a reduction in symptoms, but this association did not reach significance (p = 0.059). Changes in diffusion tensor imaging metrics did not | 873 TRILLINGSGAARD NAESS-SCHMIDT eT AL.
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