Fact or Fiction-Accelerometry Versus Self-Report in Adherence to Pediatric Concussion Protocols: Prospective Longitudinal Cohort Study.

Background: Concussion, or mild traumatic brain injury, is a growing public health concern, affecting approximately 1.2% of the population annually. Among children aged 1-17 years, concussion had the highest weighted prevalence compared to other injury types, highlighting the importance of addressing this issue among the youth population. Objective: This study aimed to assess adherence to Return to Activity (RTA) protocols among youth with concussion and to determine if better adherence affected time to recovery and the rate of reinjury. Methods: Children and youth (N=139) aged 5-18 years with concussion were recruited. Self-reported symptoms and protocol stage of recovery were monitored every 48 hours until symptom resolution was achieved. Daily accelerometry was assessed with the ActiGraph. Data were collected to evaluate adherence to the RTA protocol based on physical activity cutoff points corresponding to RTA stages. Participants were evaluated using a battery of physical, cognitive, and behavioral measures at recruitment, upon symptom resolution, and 3 months post symptom resolution. Results: For RTA stage 1, a total of 13% of participants were adherent based on accelerometry, whereas 11% and 34% of participants were adherent for stage 2 and 3, respectively. The median time to symptom resolution was 13 days for participants who were subjectively reported adherent to the RTA protocol and 20 days for those who were subjectively reported as nonadherent (P=.03). No significant agreement was found between self-report of adherence and objective actigraphy adherence to the RTA protocol as well as to other clinical outcomes, such as depression, quality of life, and balance. The rate of reinjury among the entire cohort was 2% (n=3). Conclusions: Overall, adherence to staged protocols post concussion was minimal when assessed with accelerometers, but adherence was higher by self-report. More physical activity restrictions, as specified in the RTA protocol, resulted in lower adherence. Although objective adherence was low, reinjury rate was lower than expected, suggesting a protective effect of being monitored and increased youth awareness of protocols. The results of this study support the move to less restrictive protocols and earlier resumption of daily activities that have since been implemented in more recent protocols.

Hot-Band Absorption Can Mimic Entangled Two-Photon Absorption.

It has been proposed that entangled two-photon absorption (E2PA) can be observed with up to 1010 lower photon flux than its classical counterpart, therefore enabling ultralow-power two-photon fluorescence microscopy. However, there is a significant controversy regarding the magnitude of this quantum enhancement in excitation efficiency. We investigated the fluorescence signals from Rhodamine 6G and LDS798 excited with a CW laser or an entangled photon pair source at ∼1060 nm. We observed a signal that originates from hot-band absorption (HBA), which is one-photon absorption from thermally populated vibrational levels of the ground electronic state. This mechanism, which has not been previously discussed in the context of E2PA, produces a signal with a linear power dependence, as would be expected for E2PA. For the typical conditions under which E2PA measurements are performed, contributions from the HBA process could lead to a several orders of magnitude overestimate of the quantum advantage.

Witnessing the survival of time-energy entanglement through biological tissue and scattering media.

We demonstrate the preservation of the time-energy entanglement of near-IR photons through thick biological media (≤1.55 mm) and tissue (≤ 235 µm) at room temperature. Using a Franson-type interferometer, we demonstrate interferometric contrast of over 0.9 in skim milk, 2% milk, and chicken tissue. This work supports the many proposed opportunities for nonclassical light in biological imaging and analyses from sub-shot noise measurements to entanglement-enhanced fluorescence imaging, clearly indicating that the entanglement characteristics of photons can be maintained even after propagation through thick, turbid biological samples.

Pain, Depression, and Posttraumatic Stress Disorder Following Major Extremity Trauma Among United States Military Serving in Iraq and Afghanistan: Results From the Military Extremity Trauma and Amputation/Limb Salvage Study.

OBJECTIVES: Assess the burden and co-occurrence of pain, depression, and posttraumatic stress disorder (PTSD) among service members who sustained a major limb injury, and examine whether these conditions are associated with functional outcomes. DESIGN: A retrospective cohort study. SETTING: Four U.S. military treatment facilities: Walter Reed Army Medical Center, National Naval Medical Center, Brooke Army Medical Center, and Naval Medical Center San Diego. PATIENTS/PARTICIPANTS: Four hundred twenty-nine United States service members who sustained a major limb injury while serving in Afghanistan or Iraq met eligibility criteria upon review of their medical records. INTERVENTION: Not applicable. MAIN OUTCOME MEASUREMENTS: Outcomes assessed were: function using the short musculoskeletal functional assessment; PTSD using the PTSD Checklist and diagnostic and statistical manual criteria; pain using the chronic pain grade scale. RESULTS: Military extremity trauma and amputation/limb salvage patients without pain, depression, or PTSD, were, on average, about one minimally clinically important difference (MCID) from age- and gender-adjusted population norms. In contrast, patients with low levels of pain and no depression or PTSD were, on average, one to 2 MCIDs from population norms. Military extremity trauma and amputation/limb salvage patients with either greater levels of pain, and who experience PTSD, depression, or both, were 4 to 6 MCIDs from population norms. Regression analyses adjusting for injury type (upper or lower limb, salvage or amputation, and unilateral or bilateral), age, time to interview, military rank, presence of a major upper limb injury, social support, presence of mild traumatic brain injury/concussion, and combat experiences showed that higher levels of pain, depression, and PTSD were associated with lower one-year functional outcomes. CONCLUSIONS: Major limb trauma sustained in the military results in significant long-term pain and PTSD. Overall, the results are consistent with the hypothesis that pain, depression, and PTSD are associated with disability in this population. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Experimental Low-Latency Device-Independent Quantum Randomness.

Applications of randomness such as private key generation and public randomness beacons require small blocks of certified random bits on demand. Device-independent quantum random number generators can produce such random bits, but existing quantum-proof protocols and loophole-free implementations suffer from high latency, requiring many hours to produce any random bits. We demonstrate device-independent quantum randomness generation from a loophole-free Bell test with a more efficient quantum-proof protocol, obtaining multiple blocks of 512 random bits with an average experiment time of less than 5 min per block and with a certified error bounded by 2^{-64}≈5.42×10^{-20}.

Concussion Management for Children Has Changed: New Pediatric Protocols Using the Latest Evidence.

Return to activity (RTA) and return to school (RTS) are important issues in pediatric concussion management. This study aims to update CanChild's 2015 RTA and RTS protocols, on the basis of empirical data and feedback collected from our recently completed prospective cohort study, focusing on concussed children and their caregivers; systematic review of evidence published since 2015; and consultation with concussion management experts. The new protocols highlight differences from the earlier versions, mainly, (1) symptom strata to allow quicker progression for those who recover most quickly; (2) a shortened rest period (24-48 hours) accompanied by symptom-guided activity; (3) the recommendation that children progress through the stages before they are symptom free, if symptoms have decreased and do not worsen with activity; (4) specific activity suggestions at each stage of the RTA protocol; (5) recommendations for the amount of time to spend per stage; and (6) integration of RTS and RTA.

Does early antipsychotic response predict long-term treatment outcome?

OBJECTIVE: Early antipsychotic response within the first 2-3 weeks of treatment can predict short-term outcomes after several months. We conducted the current study to determine whether the predictive value of early antipsychotic response persists throughout long-term treatment over multiple years. METHODS: In this observational study, we conducted follow-up assessments of 64 patients with first-episode psychosis an average of 25 months after they began antipsychotic treatment. Patients were initially randomized to receive haloperidol or olanzapine, but treatment after the acute hospitalization period was not controlled. Regression analyses were used to determine whether early improvement on the Brief Psychiatric Rating Scale at 2 or 3 weeks predicted longer term improvement at follow-up. We conducted secondary analyses to determine whether early response could predict extrapyramidal side effects at follow-up. RESULTS: Early response to haloperidol at 2 weeks predicted Brief Psychiatric Rating Scale improvement on longer term follow-up (p = .002). Longer term improvement was not predicted by early response to olanzapine at 2 weeks (p = .726) or 3 weeks (p = .541). Rates of extrapyramidal side effects did not differ between treatment groups and were not predicted by early response. CONCLUSION: These results demonstrate the long-term prognostic value of early haloperidol response. The predictive value of early olanzapine response may be less robust.

The Relationship Between Early Haloperidol Response and Associated Extrapyramidal Side Effects.

BACKGROUND: Early response to antipsychotic medication within 2 weeks of initiating treatment can predict psychiatric outcomes. However, it is unclear whether early response is also predictive of extrapyramidal side effects (EPSs) associated with antipsychotic medications. METHODS: In this study, we investigated 136 consecutive antipsychotic-naive, first-episode psychosis patients naturalistically treated with haloperidol. Patients were assessed at baseline and weekly after treatment initiation using the Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Dystonia, parkinsonism, akathisia, and dyskinesia were also assessed weekly using standardized rating scales. Regression analyses were used to determine whether early response at week 2 of treatment predicted the incidence of EPS at any point during hospitalization. A secondary analysis was conducted to determine whether early response continued to predict EPS in patients who experienced no EPS within the first 2 weeks of treatment. RESULTS: The analyses demonstrated that greater Brief Psychiatric Rating Scale percent improvement at week 2 predicted a decreased risk of EPSs (P = 0.004), even in patients who did not show any EPSs within the first 2 weeks of treatment (P = 0.005). For specific EPS, early response predicted decreased incidences of parkinsonism (P = 0.028) and dyskinesia (P = 0.025), but not akathisia or dystonia. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale improvement at week 2 did not predict EPSs. In addition, EPSs were not predicted by the maximum antipsychotic dose received during hospitalization. CONCLUSIONS: These results indicate that early antipsychotic response is valuable not only for predicting psychiatric outcomes, but also for predicting the risk of EPSs.

An experimental test of noncontextuality without unphysical idealizations.

To make precise the sense in which nature fails to respect classical physics, one requires a formal notion of classicality. Ideally, such a notion should be defined operationally, so that it can be subject to direct experimental test, and it should be applicable in a wide variety of experimental scenarios so that it can cover the breadth of phenomena thought to defy classical understanding. Bell's notion of local causality fulfils the first criterion but not the second. The notion of noncontextuality fulfils the second criterion, but it is a long-standing question whether it can be made to fulfil the first. Previous attempts to test noncontextuality have all assumed idealizations that real experiments cannot achieve, namely noiseless measurements and exact operational equivalences. Here we show how to devise tests that are free of these idealizations. We perform a photonic implementation of one such test, ruling out noncontextual models with high confidence.

The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine.

Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine.

Catatonia: Our current understanding of its diagnosis, treatment and pathophysiology.

Catatonia is a psychomotor syndrome that has been reported to occur in more than 10% of patients with acute psychiatric illnesses. Two subtypes of the syndrome have been identified. Catatonia of the retarded type is characterized by immobility, mutism, staring, rigidity, and a host of other clinical signs. Excited catatonia is a less common presentation in which patients develop prolonged periods of psychomotor agitation. Once thought to be a subtype of schizophrenia, catatonia is now recognized to occur with a broad spectrum of medical and psychiatric illnesses, particularly affective disorders. In many cases, the catatonia must be treated before any underlying conditions can be accurately diagnosed. Most patients with the syndrome respond rapidly to low-dose benzodiazepines, but electroconvulsive therapy is occasionally required. Patients with longstanding catatonia or a diagnosis of schizophrenia may be less likely to respond. The pathobiology of catatonia is poorly understood, although abnormalities in gamma-aminobutyric acid and glutamate signaling have been suggested as causative factors. Because catatonia is common, highly treatable, and associated with significant morbidity and mortality if left untreated, physicians should maintain a high level of suspicion for this complex clinical syndrome. Since 1989, we have systematically assessed patients presenting to our psychiatry service with signs of retarded catatonia. In this paper, we present a review of the current literature on catatonia along with findings from the 220 cases we have assessed and treated.

Cushing Disease Presenting as Primary Psychiatric Illness: A Case Report and Literature Review.

We report the case of a woman with long-standing refractory depression and psychotic features who was eventually diagnosed with Cushing disease. After surgical treatment of a pituitary adenoma, she experienced gradual psychiatric recovery and was eventually able to discontinue all psychotropic medication. We review the psychiatric components of Cushing disease, implications of psychiatric illnesses for the treatment and prognosis of Cushing disease, and potential pathophysiological mechanisms linking glucocorticoid excess to psychiatric illness.

The Military Extremity Trauma Amputation/Limb Salvage (METALS) study: outcomes of amputation versus limb salvage following major lower-extremity trauma.

BACKGROUND: The study was performed to examine the hypothesis that functional outcomes following major lower-extremity trauma sustained in the military would be similar between patients treated with amputation and those who underwent limb salvage. METHODS: This is a retrospective cohort study of 324 service members deployed to Afghanistan or Iraq who sustained a lower-limb injury requiring either amputation or limb salvage involving revascularization, bone graft/bone transport, local/free flap coverage, repair of a major nerve injury, or a complete compartment injury/compartment syndrome. The Short Musculoskeletal Function Assessment (SMFA) questionnaire was used to measure overall function. Standard instruments were used to measure depression (the Center for Epidemiologic Studies Depression Scale), posttraumatic stress disorder (PTSD Checklist-military version), chronic pain (Chronic Pain Grade Scale), and engagement in sports and leisure activities (Paffenbarger Physical Activity Questionnaire). The outcomes of amputation and salvage were compared by using regression analysis with adjustment for age, time until the interview, military rank, upper-limb and bilateral injuries, social support, and intensity of combat experiences. RESULTS: Overall response rates were modest (59.2%) and significantly different between those who underwent amputation (64.5%) and those treated with limb salvage (55.4%) (p = 0.02). In all SMFA domains except arm/hand function, the patients scored significantly worse than population norms. Also, 38.3% screened positive for depressive symptoms and 17.9%, for posttraumatic stress disorder (PTSD). One-third (34.0%) were not working, on active duty, or in school. After adjustment for covariates, participants with an amputation had better scores in all SMFA domains compared with those whose limbs had been salvaged (p < 0.01). They also had a lower likelihood of PTSD and a higher likelihood of being engaged in vigorous sports. There were no significant differences between the groups with regard to the percentage of patients with depressive symptoms, pain interfering with daily activities (pain interference), or work/school status. CONCLUSIONS: Major lower-limb trauma sustained in the military results in significant disability. Service members who undergo amputation appear to have better functional outcomes than those who undergo limb salvage. Caution is needed in interpreting these results as there was a potential for selection bias.

Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case-control study using proton magnetic resonance spectroscopy.

BACKGROUND: Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. Metabolic abnormalities in brain areas associated with cognitive functions could give rise to neuropsychiatric symptomatology. The aim of this study was to use single-voxel proton magnetic resonance spectroscopy to identify metabolic abnormalities in regions implicated in neuropsychiatric symptoms in patients with mitochondrial disorders. METHODS: N-acetyl-aspartate and creatine levels were measured in the caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with mitochondrial disorders compared with 15 healthy controls matched for age and sex. RESULTS: N-acetyl-aspartate levels were significantly lower in the caudate nucleus among patients with mitochondrial disorders (mean 7.04 ± 1.19 standard deviation [SD] institutional units) compared with healthy controls (mean 8.19 ± 1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate nucleus among patients compared with controls (patients: mean 6.84 ± 1.42 SD institutional units; controls: mean 7.52 ± 0.76 SD institutional units; p = 0.03), but the results were no longer significant after correction for multiple comparisons. There were no significant differences in metabolite measurements between patients and controls in the anterior cingulate cortex and the hippocampus. INTERPRETATION: Metabolic abnormalities were identified exclusively in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among patients compared with controls. These results suggest that the corpus striatum may be highly susceptible to mitochondrial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive functions, our findings raise the possibility that metabolic abnormalities in the caudate nucleus may contribute to cognitive impairment and neuropsychiatric symptoms in patients with mitochondrial disorders, which could be investigated in future studies.

Bone transport combined with locking bridge plate fixation for the treatment of tibial segmental defects: a report of 2 cases.

Segmental tibial bone loss, specifically in the setting of high-energy trauma, presents a challenging problem to the treating orthopaedic surgeon. These injuries are often complicated by tissue loss, poor wound healing, and infection. Many techniques of reconstruction have been advocated from bone grafting to bone transport. Transport can accomplished using Ilizarov frames, monolateral external fixators, and intramedullary devices. Although transport over an intramedullary device offers the advantage of rigidity and controlled alignment, many authors consider prolonged external fixation and history of pin tract infection to be contraindications to this technique. To our knowledge, bone segment transport used in combination with locking plate fixation has not been described for the treatment of tibial bone defects. We describe two cases of bone transport using a combination of locked plate fixation and a monolateral external fixation frame for large tibial bone defects. This technique allows for easy correction of length and alignment, stable fixation, facilitates quicker, and easier frame removal and also allows for compression of transported segment at the time of docking.

The psychiatric presentation of mitochondrial disorders in adults.

Although comorbid psychiatric illness is increasingly being recognized in patients with mitochondrial disorders, there has been relatively little attention to psychiatric symptomatology as the primary clinical presentation. The authors report detailed clinical, biochemical, neuroradiological, and genetic findings in a series of 12 patients with mitochondrial disorders in whom psychiatric symptoms were a prominent aspect of the clinical presentation. The psychiatric presentations included depression, anorexia nervosa, bipolar disorder, and obsessive-compulsive disorder. A review of the literature, in conjunction with the present series, indicates that psychiatric symptoms can be the presenting feature of mitochondrial disorders and highlights the importance of considering this diagnosis.

The mitochondrial genome and psychiatric illness.

Psychiatric disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Searches for a genetic cause of bipolar disorder, schizophrenia, and major depressive disorder have yielded inconclusive results. There is increasing interest in the possibility that defects in the mitochondrial genome may play an important role in psychiatric illness. We undertook a review of the literature investigating mitochondria and adult psychiatric disorders. MEDLINE, PsycINFO, and EMBASE were searched from their inception through September 2011, and the reference lists of identified articles were reviewed for additional studies. While multiple lines of evidence, including clinical, genetic, ultrastructural, and biochemical studies, support the involvement of mitochondria in the pathophysiology of psychiatric illness, many studies have methodological limitations and their findings have not been replicated. Clinical studies suggest that psychiatric features can be prominent, and the presenting features of mitochondrial disorders. There is limited but inconsistent evidence for the involvement of mitochondrial DNA haplogroups and mitochondria-related nuclear gene polymorphisms, and for mitochondrial ultrastructural and biochemical abnormalities in psychiatric illness. The current literature suggests that mitochondrial dysfunction and mitochondrial genetic variations may play an important role in psychiatric disorders, but additional methodologically rigorous and adequately powered studies are needed before definitive conclusions can be drawn.

The psychiatric manifestations of mitochondrial disorders: a case and review of the literature.

OBJECTIVE: Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES: This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271. We also searched the literature for all case reports of patients with mitochondrial disorders who initially present with prominent psychiatric symptoms by using MEDLINE (from 1948-February 2011), Embase (from 1980-February 2011), PsycINFO (from 1806-February 2011), and the search terms mitochondrial disorder, mitochondria, psychiatry, mental disorders, major depression, anxiety, schizophrenia, and psychosis. STUDY SELECTION: Fifty cases of mitochondrial disorders with prominent psychiatric symptomatology were identified. DATA EXTRACTION: Information about the psychiatric presentation of the cases was extracted. This information was combined with our case, the most common psychiatric manifestations of mitochondrial disorders were identified, and the important diagnostic and treatment implications for patients with psychiatric illness were reviewed. RESULTS: The most common psychiatric presentations in the cases of mitochondrial disorders included mood disorder, cognitive deterioration, psychosis, and anxiety. The most common diagnosis (52% of cases) was a MELAS mutation. Other genetic mitochondrial diagnoses included polymerase gamma mutations, Kearns-Sayre syndrome, mitochondrial DNA deletions, point mutations, twinkle mutations, and novel mutations. CONCLUSIONS: Patients with mitochondrial disorders can present with primary psychiatric symptomatology, including mood disorder, cognitive impairment, psychosis, and anxiety. Psychiatrists need to be aware of the clinical features that are indicative of a mitochondrial disorder, investigate patients with suggestive presentations, and be knowledgeable about the treatment implications of the diagnosis.