The effect of age on functional outcome in mild traumatic brain injury: 6-month report of a prospective multicenter trial

OBJECTIVE: Elderly patients (aged 60 years and older) have been demonstrated to have an increased mortality after isolated traumatic brain injury (TBI); however, the prognosis of those patients surviving their hospitalization is unknown. We hypothesized that surviving elderly patients would also have decreased functional outcome, and this study examined the functional outcome of patients with isolated TBI at discharge and at 6 months posthospitalization. METHODS: This was a multicenter prospective study of all patients with isolated moderate to severe TBI defined as Head Abbreviated Injury Scale score of 3 with an Abbreviated Injury Scale score in any other body area of 1. Patients surviving to discharge gave their consent and were enrolled. Data collected included demographics, Glasgow Coma Scale (GCS) score at admission, and neurosurgical interventions. Outcome data included discharge disposition and Glasgow Outcome Scale score and modified Functional Independence Measure (FIM) score at discharge and at 6 months. RESULTS: Two hundred thirty-five patients were enrolled, with 44 (19%) aged greater than or equal to 65 years. Mechanisms of injury were falls (34%), assaults (28%), motor vehicle collisions (14%), pedestrian (11%), and other (12%). Falls were more common in the older patients and assaults in the younger group. The mean admitting GCS score was 12.8 (95% confidence interval [CI], 12.4-13.3), with older patients having a higher mean GCS score, 14.1 (95% CI, 13.6-14.6) versus 12.5 (95% CI, 12.0-13.1; p = 0.03). There were no differences in the percentage of patients admitted to the intensive care unit or requiring neurosurgical intervention between younger and older patients. Because there were few elderly patients with low GCS scores who survived to discharge, outcome measures focused on those patients with GCS scores of 13 to 15. A greater percentage of elderly were discharged to rehabilitation (28% vs. 16%, p =0.08). The mean discharge FIM score was 10.4 (95% CI, 9.8-11.0) for the elderly versus 11.4 (95% CI, 11.1-11.7) for the young (p =0.001), with 68% elderly and 89% young discharged with total independent scores of 11 to 12. At 6 months, the difference narrowed, but the mean FIM score was still greater for the young group, 11.7 (95% CI, 11.6-11.9) versus 11.0 (95% CI, 10.6-11.4; p < 0.001). CONCLUSION: Functional outcome after isolated mild TBI as measured by the Glasgow Outcome Scale and modified FIM is generally good to excellent for both elderly and younger patients. Older patients required more inpatient rehabilitation and lagged behind their younger counterparts but continued to recover and improve after discharge. Although there were statistically significant differences in the FIM score at both discharge and 6 months, the clinical importance of these small differences in the mean FIM score to the patient's quality of life is less clear. Measurable improvement in functional status during the first 6 months after injury is observed in both groups. Aggressive management and care of older patients with TBI is warranted, and efforts should be made to decrease inpatient mortality. Continued follow-up is ongoing to determine whether these outcomes persist at 12 months.     

Developing measures of surgeons' equipoise to assess the feasibility of randomized controlled trials in vascular surgery

Background

Equipoise is defined medically as a state of genuine uncertainty about the relative benefits of alternative treatment options. This study investigated individual and collective equipoise among vascular surgeons for controversial clinical questions to assess the feasibility of conducting randomized controlled trials.

Methods

Vascular surgeons throughout Australia and New Zealand received a survey by mail.

Results

Vascular surgeons (n = 146, 77% response fraction) were able to quantify the strength of their treatment preferences and did so differentially between clinical scenarios using a simple scale. Almost one quarter (24%; 95% CI, 18%-32%) were completely undecided about whether carotid endarterectomy or carotid stenting was preferable to treat carotid stenosis in high-risk patients, indicating individual equipoise. In contrast, the vast majority of respondents (89%; 95% CI, 82%-93%) favored carotid endarterectomy over carotid stenting for average-risk patients, suggesting lack of community equipoise for this patient group. Similarly, there was lack of community equipoise for treatments for abdominal aortic aneurysm in high-risk patients with 88% (95% CI, 81%-92%) favoring a minimally invasive approach. Older respondents were consistently less willing to take part in randomized trials, with strength of treatment preference also independently predicting willingness to participate in 4 of 6 trials.

Conclusions

Individual and community equipoise can be measured in a representative sample of surgeons as part of the feasibility assessment for future randomized controlled trials.     

Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury

The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood–brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings.

     

Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia

Objectives:

This trial was conducted to test the effects of an alpha7 nicotinic receptor full agonist, TC-5619, on negative and cognitive symptoms in subjects with schizophrenia.

Methods:

In 64 sites in the United States, Russia, Ukraine, Hungary, Romania, and Serbia, 477 outpatients (18–65 years; male 62%; 55% tobacco users) with schizophrenia, treated with a new-generation antipsychotic, were randomized to 24 weeks of placebo (n = 235), TC-5619, 5mg (n = 121), or TC-5619, 50mg (n = 121), administered orally once daily. The primary efficacy measure was the Scale for the Assessment of Negative Symptoms (SANS) composite score. Key secondary measures were the Cogstate Schizophrenia Battery (CSB) composite score and the University of California San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) total score. Secondary measures included: Positive and Negative Syndrome Scale in Schizophrenia (PANSS) total and subscale scores, SANS domain scores, CSB item scores, Clinical Global Impression-Global Improvement (CGI-I) score, CGI-Severity (CGI-S) score, and Subject Global Impression-Cognition (SGI-Cog) total score.

Results:

SANS score showed no statistical benefit for TC-5619 vs placebo at week 24 (5mg, 2-tailed P = .159; 50mg, P = .689). Likewise, no scores of CSB, UPSA-B, PANSS, CGI-I, CGI-S, or SGI-Cog favored TC-5619 (P > .05). Sporadic statistical benefit favoring TC-5619 in some of these outcome measures were observed in tobacco users, but these benefits did not show concordance by dose, country, gender, or other relevant measures. TC-5619 was generally well tolerated.

Conclusion:

These results do not support a benefit of TC-5619 for negative or cognitive symptoms in schizophrenia.Key words: schizophrenia, negative symptoms, cognition     

Characteristics of HER2-positive breast cancer diagnosed following the introduction of universal HER2 testing

The aim of this study was to determine the impact of universal HER2 testing on the clinico-pathologic profile of HER2+ breast cancer. Data were extracted from breast cancer pathology reports spanning two periods: before (2003/4, n = 379), and after (2008/9, n = 560) the introduction of universal testing. In 2003/4, 43.3% of breast cancers were tested for HER2 with 16% of tested cases HER2+. In 2008/9, 98.4% of cases were tested with 14.7% HER2+. In 2008/9, HER2+ status was associated with younger age, higher grade, increased tumour size, lymph node involvement, negative oestrogen and/or progesterone receptor status. HER2+ cases diagnosed in 2003/4 were not significantly different in respect of these features. The rate of HER2+ breast cancer amongst screen detected cases in 2008/9 was 8.3%. The phenotype of HER2+ breast cancer was stable following the introduction of universal testing. The overall rate of HER2+ breast cancer was influenced by screen detection.     

MRI of the Hip for the evaluation of femoroacetabular impingement; past,present, and future

The concept of femoroacetabular impingement (FAI) has, in a relatively short time, come to the forefront of orthopedic imaging. In just a few short years MRI findings that were in the past ascribed to degenerative change, normal variation, or other pathologies must now be described and included in radiology reports, as they have been shown, or are suspected to be related to, FAI. Crucial questions have come up in this time, including: what is the relationship of bony morphology to subsequent cartilage and labral damage, and most importantly, how is this morphology related to the development of osteoarthritis? In this review, we attempt to place a historical perspective on the controversy, provide guidelines for interpretation of MRI examinations of patients with suspected FAI, and offer a glimpse into the future of MRI of this complex condition. J. Magn. Reson. Imaging 2015;41:558–572. © 2014 Wiley Periodicals, Inc.     

Successful nonoperative management of chronic osteoarthritis pain of the knee: safety and efficacy of retreatment with intra-articular hyaluronans

CONTEXT: Although there are many nonsurgical therapies available for the treatment of pain associated with osteoarthritis (OA), their long-term use and safety have not been systematically followed. Intra-articular hyaluronan therapy has been used in the treatment of symptoms associated with OA of the knee with a very favorable safety profile. Five intra-articular hyaluronan products are approved in the US. No systematic review of the safety and efficacy of their chronic use has been reported. OBJECTIVE: To evaluate the literature on the efficacy and safety of repeat courses of hyaluronan therapy in patients with OA of the knee. DATA SOURCES: MEDLINE, EMBASE, searched through October 2004. STUDY SELECTION: Databases were searched using the terms hyaluronan, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, osteoarthritis, adverse events, repeat treatment, and multiple courses. DATA SYNTHESIS: There are some data that support the benefit and safety of repeat treatment for all products. Data also indicate that one formulation of sodium hyaluronate (molecular weight [MW] 500-730 kDa) is well tolerated and as effective after multiple courses of treatment as it is after a single course. There is also clinical evidence that prolonged use of sodium hyaluronate (MW 500-730 kDa) may significantly decrease the rate of deterioration of joint structure. Localized severe acute inflammatory reactions reported with repeated treatment in some patients are not a class effect but may be linked to physicochemical characteristics of hylan-based treatment. CONCLUSIONS: Repeat courses of the hyaluronans are safe and effective in the treatment of pain associated with OA of the knee.     

Graft Distortion After Endovascular Repair of Abdominal Aortic Aneurysm: Association with Sac Morphology and Mid-Term Complications

Purpose: To investigate the incidence, significance, and mechanism of stent-graft distortion after endovascular repair (EVR) of abdominal aortic aneurysm. Methods: EVR of abdominal aortic aneurysm was performed in 51 cases (49 modular, bifurcated; 2 tube). Thirty-two patients were followed for 6 or more months and had equivalent baseline and follow-up images which could be used to determine changes in graft configuration. Sac dimensions were measured using computed tomographic (CT) images and graft-related complications were recorded. Results: Amongst 32 patients evaluated on follow-up, there was graft distortion in 24. Distorted grafts were significantly (p= 0.002) associated with sac diameter reduction (mean 5 mm) and sac length reduction (mean 8.1 mm). All graft-related complications occurred in the limbs of eight distorted grafts, with a mean reduction of sac length in this group of 7.8 mm on reformatted CT images. Conclusion: There was a highly significant association between graft distortion and limb complications, and reduced sac dimensions.     

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2–4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae.In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalized bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity).Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4–5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.     

Sir George Newman (1870-1948)

George Newman (1870-1948) was a major figure in the development of public health and school medicine in the years between World Wars I and II. From a Quaker background, he became first Chief Medical Officer to the Board of Education and then Chief Medical Officer to the Ministry of Health. In these posts he wrote many reports to the minister concerned and stimulated others. He educated the public in health matters with notable literary skill. He remained an active Quaker all his life.