A close association of freedom from pain,migraine-related functional disability,and other outcomes: results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN

BackgroundWhile pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.MethodsPatient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.ResultsPatients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.ConclusionsThis study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.Trial RegistrationSAMURAI ({"type":"clinical-trial","attrs":{"text":"NCT02439320","term_id":"NCT02439320"}}NCT02439320); SPARTAN ({"type":"clinical-trial","attrs":{"text":"NCT02605174","term_id":"NCT02605174"}}NCT02605174).Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01303-w.     

Resting‐state functional connectivity after concussion is associated with clinical recovery

There has been a recent call for longitudinal imaging studies to better characterize the time course of physiological recovery following sport‐related concussion (SRC) and its relationship with clinical recovery. To address this, we evaluated changes to resting‐state functional connectivity (rs‐FC) of the whole‐brain network following SRC and explored associations between rs‐FC and measures of clinical outcome. High school and collegiate football athletes were enrolled during preseason. Athletes that suffered SRC (N = 62) were assessed across the acute (within 48 hr) and sub‐acute (days 8, 15, and 45) phases. Matched football athletes without concussion served as controls (N = 60) and participated in similar visits. Multi‐band resting‐state fMRI was used to assess whole‐brain rs‐FC at each visit using network‐based statistic and average nodal strength from regions of interest defined using a common whole‐brain parcellation. Concussed athletes had elevated symptoms, psychological distress, and oculomotor, balance, and memory deficits at 48 hr postconcussion relative to controls, with diminished yet significant elevations in symptoms and psychological distress at 8 days. Both rs‐FC analyses showed that concussed athletes had a global increase in connectivity at 8 days postconcussion relative to controls, with no differences at the 48‐hr, 15‐day, or 45‐day visits. Further analysis revealed the group effect at the 8‐day visit was driven by the large minority of concussed athletes still symptomatic at their visit; asymptomatic concussed athletes did not differ from controls. Findings from this large‐scale, prospective study suggest whole‐brain rs‐FC alterations following SRC are delayed in onset but associated with the presence of self‐reported symptoms.     

Are physician and non-physician providers of outpatient mental healthcare substitutes or complements? a conceptual clarification

Solving the health care consumers’ (producers’) utility maximization (cost minimization) problem could entail the substitution of alternative care providers (factor inputs) when the relative out-of-pocket costs (factor prices) change, ceteris paribus. The conceptual advancement in this contribution is illustrated with an earlier paper (P. Deb and A. Holmes, Health Economics 7(4):347–362, 1998) on the economic relationship of physicians (M.D.s) and ‘other providers’ (Ph.D.s, other) in the US outpatient demand for mental health care services. Many aspects of our conceptual progress are insightful. Foremost, our conclusion on whether M.D. and non-M.D. providers of outpatient mental health care are economic complements or substitutes depends on the alternative measure of the substitution elasticity used. Second, when correctly measured the expenditure-minimizing substitutions among mental health providers can be useful policy decision guides for consumers covered under traditional indemnity insurance with deductibles or managed care plans with user co-payments. Finally, our conceptual clarification should motivate future investigators of health services demand (or use) and cost models to consider a wider conceptual foundation for assessing the structure and implications of provider relationships.