Safety evaluation of a milk-based protein powder produced by a novel manufacturing technique.

TruActive™ NF is a novel, fat-free, milk-based protein powder to be added to food to increase protein content and is manufactured using non-thermal treatment to reduce potential pathogens most relevant to protecting public health. TruActive™ NF was evaluated for potential pathogens of concern to public health regulators; none were detected. The estimated daily intake (EDI) of TruActive™ NF at a 90th percentile consumption for the powder in nutritional beverages and bars is 14,700 mg/day. In vitro genotoxicity testing revealed that concentrations of TruActive™ NF up to 5000 µg/plate did not induce point mutations in selected strains. Oral administration of TruActive™ NF to male Sprague-Dawley rats in an in vivo mammalian chromosomal aberration assay did not induce chromosomal aberrations or significantly affect mitosis in bone marrow cells at 2000 mg/kg. Male and female Sprague-Dawley rats were administered TruActive™ NF at concentrations of 7.5%, 15%, and 30% of the diet during a 28-day subacute dietary study followed by a 14-day recovery period. Some parameters were altered at the 30% diet concentration. The No Observed Adverse Effect Level (NOAEL) in the 28-day dietary study was at 15% of the diet (11,812 mg/kg bw/day for male rats and 11,521 mg/kg bw/day for female rats).

Systematic literature review of imaging features of spinal degeneration in asymptomatic populations.

BACKGROUND AND PURPOSE: Degenerative changes are commonly found in spine imaging but often occur in pain-free individuals as well as those with back pain. We sought to estimate the prevalence, by age, of common degenerative spine conditions by performing a systematic review studying the prevalence of spine degeneration on imaging in asymptomatic individuals. MATERIALS AND METHODS: We performed a systematic review of articles reporting the prevalence of imaging findings (CT or MR imaging) in asymptomatic individuals from published English literature through April 2014. Two reviewers evaluated each manuscript. We selected age groupings by decade (20, 30, 40, 50, 60, 70, 80 years), determining age-specific prevalence estimates. For each imaging finding, we fit a generalized linear mixed-effects model for the age-specific prevalence estimate clustering in the study, adjusting for the midpoint of the reported age interval. RESULTS: Thirty-three articles reporting imaging findings for 3110 asymptomatic individuals met our study inclusion criteria. The prevalence of disk degeneration in asymptomatic individuals increased from 37% of 20-year-old individuals to 96% of 80-year-old individuals. Disk bulge prevalence increased from 30% of those 20 years of age to 84% of those 80 years of age. Disk protrusion prevalence increased from 29% of those 20 years of age to 43% of those 80 years of age. The prevalence of annular fissure increased from 19% of those 20 years of age to 29% of those 80 years of age. CONCLUSIONS: Imaging findings of spine degeneration are present in high proportions of asymptomatic individuals, increasing with age. Many imaging-based degenerative features are likely part of normal aging and unassociated with pain. These imaging findings must be interpreted in the context of the patient's clinical condition.

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

Local Anesthesia with Bupivacaine and Lidocaine for Vertebral Fracture trial (LABEL): a report of outcomes and comparison with the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST).

BACKGROUND AND PURPOSE: INVEST is a recently published double-blind placebo controlled randomized trial that demonstrated similar improvements in pain between blinded vertebroplasty and sham-vertebroplasty groups. LABEL is a trial determining the efficacy of pain relief of an injection of lidocaine and bupivacaine at the site of painful osteoporotic vertebral compression fractures in unblinded patients. We compared outcomes from the unblinded LABEL trial with those of blinded control patients from the lead site of the INVEST, exploring the role of blinding on the benefit of local anesthesia infusion for painful vertebral compression fractures. MATERIALS AND METHODS: Nineteen patients with painful osteoporotic vertebral compression fractures underwent unblinded injection of lidocaine and bupivacaine at the site of painful osteoporotic vertebral compression fractures. Patients were given the option of undergoing vertebroplasty at any time following the procedure. Primary outcome measures were change in the RDQ and pain (at rest, with activity, and average 24-hour pain) at days 1 and 3 following the injection. Day 3 change in RDQ scores and change in average 24-hour pain were compared for LABEL and INVEST control patients from the lead site (n = 16). RESULTS: Among patients in the LABEL trial, we detected no significant improvement in RDQ scores, pain at rest, and average 24-hour pain at days 1 and 3, whereas pain with activity improved significantly at both time points. INVEST control patients from the lead site experienced significantly greater improvement in average pain during 24 hours at days 1 (P = .03) and 3 (P = .04) and significantly greater improvements in RDQ scores at day 3 (P = .006) than patients from LABEL. CONCLUSIONS: An unblinded injection of local anesthesia is ineffective in treating pain from osteoporotic compression fractures. This suggests that factors other than local anesthesia were responsible for the observed improvement in the control group in INVEST.

Baseline pain and disability in the Investigational Vertebroplasty Efficacy and Safety Trial.

BACKGROUND AND PURPOSE: Multiple case series of vertebroplasty outcomes have been published, though no large, placebo controlled trial has yet been performed. Our aim was to report baseline characteristics for the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of vertebroplasty. MATERIALS AND METHODS: We compared baseline demographics, pain scores, and scores on the modified Roland-Morris Disability Scale (RMDS), a back pain-specific metric, between 2 groups. One group included subjects enrolled at the lead INVEST site (n = 27 to date). The second group consisted of eligible patients seen concurrently at the lead INVEST site, who declined enrollment (n = 70). Comparisons were made by using 2-sample t tests. RESULTS: Mean ages were similar between groups, averaging approximately 74 years among study participants and 77 years among nonenrolled eligible patients (P = .17). Approximately 75% of subjects were female in both groups. RMDS scores of enrolled patients at the lead site (18.0 +/- 4.2) were not statistically different from those of eligible nonenrolled patients at the lead site (18.6 +/- 3.6, P = .49). Pain scores in the enrolled subjects were measured as "average intensity over the prior 24 hours" with mean scores of 7.6 +/- 2.1 among enrolled patients at the lead site. Pain scores in eligible nonenrolled patients were measured as "pain at rest," with mean score of 3.4 +/- 3.3, and "pain with activity," with mean score of 8.5 +/- 2.0. CONCLUSIONS: Patient demographics among subjects enrolled in the INVEST are similar to those in a cohort of eligible nonenrolled patients. Back pain-specific disability was similar between subjects enrolled in the INVEST study and eligible nonenrolled patients at the lead site.

A systematic literature review of magnetic resonance spectroscopy for the characterization of brain tumors.

BACKGROUND AND PURPOSE: Proton MR spectroscopy ((1)H-MR spectroscopy) is a potentially useful adjunct to anatomic MR imaging in the characterization of brain tumors. We performed an updated systematic review of the evidence. METHODS: We employed a standardized search strategy to find studies published during 2002-2004. We reviewed studies measuring diagnostic accuracy and diagnostic, therapeutic, or health impact of (1)H-MR spectroscopy. We abstracted information on study design, (1)H-MR spectroscopy technique, and methodologic quality. We categorized studies into 5 subgroups: (1) metastasis versus high-grade tumor; (2) high-versus low-grade tumor; (3) recurrent tumor versus radiation necrosis; (4) tumor extent; and (5) tumor versus non-neoplastic lesion. RESULTS: We identified 26 studies evaluating diagnostic performance, diagnostic impact, or therapeutic impact. No articles evaluated patient health or cost-effectiveness. Methodologic quality was mixed; most used histopathology as the reference standard but did not specify blinded interpretation of histopathology. One large study demonstrated a statistically significant increase in diagnostic accuracy for indeterminate brain lesions from 55%, based on MR imaging, to 71% after analysis of (1)H-MR spectroscopy. Several studies have found that (1)H-MR spectroscopy is highly accurate for distinguishing high- and low-grade gliomas, though the incremental benefit of (1)H-MR spectroscopy in this setting is less clear. Interpretation for the other clinical subgroups is limited by the small number of studies. CONCLUSION: The current evidence on the accuracy of (1)H-MR spectroscopy in the characterization of brain tumors is promising. However, additional high-quality studies are needed to convince policy makers. We present guidelines to help focus future research in this area.

Training and research in emergency psychiatry.

In this chapter we have attempted to describe some of the issues that must be addressed in funding, designing, and running a research and training program for emergency psychiatry. Such a program serves the in-house needs of staff training, skill and morale renewal, and program evaluation. In addition it can serve as a resource for the community to train a future cadre of individuals and to seek answers that will provide a solid base of knowledge for emergency psychiatry in the future.

Crisis treatment in a day hospital. Impact on medical care-seeking.

The cost-effectiveness of a day hospital program is documented by examining the utilization of medical and psychiatric services before and after a time-limited following crisis-presentations. Patients in crisis have been shown to have increased need for services following a crisis. In contrast, medical-care events decreased for the population treated in the day hospital. The results, with respect to reduction of medical care were greatest for those patients judged to have benefited from the psychiatric interventions.

Organic versus functional etiology in catatonia: case report.

The case of an illegal alien brought to the emergency room in a catatonic stupor is described. The patient's condition worsened following the administration of a high-potency neuroleptic, and it was later learned that he had a history of epileptic seizures. This case emphasizes the importance of ruling out organic causes in patients presenting with catatonic symptoms.

Assessment of the efficacy of activated charcoal following gastric lavage in acute drug emergencies.

The efficacy of administering a slurry of 100 g of activated charcoal (AC) via the gastric tube following lavage was assessed in 25 treated and 37 control patients presenting to the emergency room with chemical evidence of sedative-hypnotics or aspirin in the blood. Efficacy was evaluated as the ability of AC to prevent further absorption as determined by subsequent blood drug concentration changes. Although fewer patients in the AC group showed increased blood drug concentrations, the differences were not statistically significant. Comparison of the mean percent change in blood drug concentrations at various times following treatment produced similar results. Comparisons using subgroups of patients based on the individual drugs, the treatment delay time, and entering functional decompensation showed significant benefit from AC only in the less symptomatic patients. Comparing these results with other studies demonstrating the unequivocal efficacy of early (e.g., 30 min) treatment, it is concluded that the use of AC following lavage may often be too late to benefit most patients. The authors suggest that AC be given in the home, emergency vehicle, or immediately upon admission.

Studies on the efficacy of gastric lavage as practiced in a large metropolitan hospital.

The efficacy of gastric lavage as it is practiced in a major metropolitan hospital was evaluated. From a population of 76 patients with chemical evidence of sedative-hypnotic drugs in the blood, two or more therapeutic doses were recovered from 15.8% of the lavage samples, and 10 or more therapeutic doses were recovered from 6.6%. In a population consisting of patients with detectable quantities of drugs in the lavage sample, diazepam and amitriptyline are more adequately recovered than the sedative-hypnotic drugs. Very poor recoveries were obtained in patients lavaged more than 2 h after ingestion except in cases of amitriptyline overdose or massive sedative-hypnotic ingestion. The study indicates that inadequate criteria are employed in selecting patients most likely to benefit from lavage. Dose, time since ingestion, and symptomatology are discussed as criteria for selection of patients for lavage.

Anomalous tendon slips from the flexor pollicis longus to the flexor digitorum profundus.

Anomalous tendon slips from the flexor pollicis longus to the flexor digitorum profundus are described. Clinical examination of 194 patients suggests that the anomaly is present in at least one extremity of 31% of individuals and in both extremities in 14%. Dissection of 43 cadavers demonstrated the anomaly in at least one extremity of 25% and in both extremities of 6%. Four cases are described in which the anomaly probably was responsible for chronic tenosynovitis. The anomaly was excised surgically in all cases.

Suicide in the 1970s: a second look.

The decade of the 70's has been reviewed with the document Suicide Prevention in the 70's serving as a guide. Twenty-one goals put forward in the report were reviewed in light of subsequent progress in the field. Although progress was noted on many fronts, four areas were outstanding in the sense that envisioned goals were met or exceeded. These involved the areas of promulgation of information about suicide, establishment of standards and certification procedures, development of regional organizations to forward training and program development, and education of the public to improve awareness of suicide as a public problem. This analysis also identified areas where little or no progress has been made. From this there developed four recommendations: 1. The funding and establishment of a national case file using a standard nomenclature and a standard data base to improve epidemiologic knowledge, and to provide pooled data appropriate for more sophisticated research analyses. 2. The establishment of a task force to study the application of program evaluation methods to suicide prevention efforts. 3. The development of new programs at local levels to try to reach known high-risk groups and to provide relevant programs of suicide prevention for them. 4. Making creative efforts toward elaboration of a comprehensive theory of life-threatening behavior and exploration of developmental corrolates of such behavior.