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Recent theorizing about the connection between the brain and trauma (Perry, 2009; Porges, 2011; van der Kolk, 2015) has led to a burgeoning of interest in the provision of music-based programs with people who have had adverse experiences. Although there has been critique of the lack of scientific basis of these theories and their implications for practice (McLean, 2016), they remain popular with practitioners who are keen to introduce innovative and potentially beneficial approaches to the people with whom they work. Music therapists have a long tradition of working with traumatized clients, however, the brain-based rationales did not seem congruent with the less predictable and more idiosyncratic benefits reported, which seem to occur through more psychodynamic mechanisms of action. In order to unravel what seemed to be a body of literature plagued by the conflation of theories, we undertook a critical interpretive synthesis of literature in the past 10 years to cross-examine the ways that music and trauma have been connected. To do this we extracted data from 36 identified articles to distinguish what music methods were used, what claims were made about benefits, what theoretical justifications were provided and how much research basis there was for the claims being made. Having systematically disentangled the various dimensions, we then constructed a spectrum of approaches that offers a logical categorization of four different ways of using music with people who have had adverse life experiences. These included using music for stabilizing, entrainment, expressive and performative purposes. Specific music-based methods were proposed for those associated with brain-based rationales, and more responsive, multi-method approaches were congruent with recovery and social change models. Future research would benefit from a more clearly articulated connection between theoretical rationale, music-based methods, benefits and research approaches. The resultant spectrum may p

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90