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Prognostic models can guide clinical management and increase statistical power in clinical trials. The availability and adequacy of prognostic models for mild traumatic brain injury (MTBI) is uncertain. The present study aimed to (1) identify and evaluate multivariable prognostic models for MTBI, and (2) determine which pre-, peri-, and early post-injury variables have independent prognostic value in the context of multivariable models. An electronic search of MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL databases for English-language MTBI cohort studies from 1970-2013 was supplemented by Web of Science citation and hand searching. This search strategy identified 7789 articles after removing duplicates. Of 182 full-text articles reviewed, 26 met eligibility criteria including (1) prospective inception cohort design, (2) prognostic information collected within 1 month post-injury, and (3) 2+variables combined to predict clinical outcome (e.g., post-concussion syndrome) at least 1 month later. Independent reviewers extracted sample characteristics, study design features, clinical outcome variables, predictor selection methods, and prognostic model discrimination, calibration, and cross-validation. These data elements were synthesized qualitatively. The present review found no multivariable prognostic model that adequately predicts individual patient outcomes from MTBI. Suboptimal methodology limits their reproducibility and clinical usefulness. The most robust prognostic factors in the context of multivariable models were pre-injury mental health and early post-injury neuropsychological functioning. Women and adults with early post-injury anxiety also have worse prognoses. Relative to these factors, the severity of MTBI had little long-term prognostic value. Future prognostic studies should consider a broad range of biopsychosocial predictors in large inception cohorts.

ATP release from astrocytes contributes to calcium ([Ca(2+)]) wave propagation and may modulate neuronal excitability. In epithelial cells and hepatocytes, cell swelling causes ATP release, which leads to the activation of a volume-sensitive Cl(-) current (I(Cl,swell)) through an autocrine pathway involving purinergic receptors. Astrocyte swelling is counterbalanced by a regulatory volume decrease, involving efflux of metabolites and activation of I(Cl,swell) and K(+) currents. We used whole cell patch-clamp recordings in cultured astrocytes to investigate the autocrine role of ATP in the activation of I(Cl,swell) by hypo-osmotic solution (HOS). Apyrase, an ATP/ADP nucleotidase, inhibited HOS-activated I(Cl,swell), whereas ATP and the P2Y agonists, ADPbetaS and ADP, induced Cl(-) currents similar to I(Cl,swell). Neither the P2U agonist, UTP nor the P2X agonist, alpha,beta-methylene ATP, were effective. BzATP was less effective than ATP, suggesting that P2X7 receptors were not involved. P2 purinergic antagonists, suramin, RB2, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) reversibly inhibited activation of I(Cl,swell), suggesting that ATP-activated P2Y1 receptors. Thus ATP release mediates I(Cl,swell) in astrocytes through the activation of P2Y1-like receptors. The multidrug resistance protein (MRP) transport inhibitors probenicid, indomethacin, and MK-571 all potently inhibited I(Cl.swell). ATP release from astrocytes in HOS was observed directly using luciferin-luciferase and MK-571 reversibly depressed this HOS-induced ATP efflux. We conclude that ATP release via MRP and subsequent autocrine activation of purinergic receptors contributes to the activation of I(Cl,swell) in astrocytes by HOS-induced swelling.

At least 3 million Americans sustain a mild traumatic brain injury (mTBI) each year, and 1 in 5 have symptoms that persist beyond 1 month. Standards of mTBI care have evolved rapidly, with numerous expert consensus statements and clinical practice guidelines published in the last 5 years. This Special Communication synthesizes recent expert consensus statements and evidenced-based clinical practice guidelines for civilians, athletes, military, and pediatric populations for clinicians practicing outside of specialty mTBI clinics, including primary care providers. The article offers guidance on key clinical decisions in mTBI care and highlights priority interventions that can be initiated in primary care to prevent chronicity.

This marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.