BDNF, relative preference, and reward circuitry responses to emotional communication.

Brain derived neurotrophic factor (BDNF) regulates neural development and synaptic transmission. We have tested the hypothesis that functional variation in the BDNF gene (Val66Met polymorphism, rs6265) affects brain reward circuitry encoding human judgment and decision-making regarding relative preference. We quantified relative preference among faces with emotional expressions (angry, fearful, sad, neutral, and happy) by a keypress procedure performed offline to measure effort traded for viewing time. Keypress-based relative preferences across the ensemble of faces were mirrored significantly by fMRI signal in the orbitofrontal cortex, amygdala, and hippocampus when passively viewing these faces. For these three brain regions, there was also a statistically significant group difference by BDNF genotype in the fMRI responses to the emotional expressions. In comparison with Val/Met heterozygotes, Val/Val individuals preferentially sought exposure to positive emotions (e.g., happy faces) and had stronger regional fMRI activation to aversive stimuli (e.g., angry, fearful, and sad faces). BDNF genotype accounted for approximately 30% of the variance in fMRI signal that mirrors keypress responses to these stimuli. This study demonstrates that functional allelic variation in BDNF modulates human brain circuits processing reward/aversion information and relative preference transactions.

The role and effectiveness of adjunctive hyperbaric oxygen therapy in the management of musculoskeletal disorders.

The management of musculoskeletal disorders is an increasing challenge to clinicians. Successful treatment relies on a wide range of multidisciplinary interventions. Adjunctive hyperbaric oxygen (HBO) therapy has been used as an orthopaedic treatment for several decades. Positive outcomes have been reported by many authors for orthopaedic infections, wound healing, delayed union and non-union of fractures, acute traumatic ischemia of the extremities, compromised grafts, and burn injuries. Severe side effects have also been reported with this therapy. To aid in the use of HBO therapy in orthopaedics, we reviewed 43 papers published in the past four decades and summarised the mechanisms, effectiveness, indications and contraindications, side effects, and cost impact of adjunctive hyperbaric oxygen therapy in the management of difficult musculoskeletal disorders. Adjunctive HBO therapy is an effective treatment modality for the management of some severe and refractory musculoskeletal problems. If appropriate candidates are carefully identified, hyperbaric oxygen is a limb- and sometimes life-saving therapy. HBO therapy significantly reduces the length of the patient's hospital stay, amputation rate, and wound care expenses. Thus, it is a cost-effective modality. A clinician must understand the side effects and risks of HBO treatment. Close monitoring throughout the treatment is warranted to minimise the risk to the patients.

Mycobacterium tuberculosis and Mycobacterium fortuitum osteomyelitis of the foot and septic arthritis of the ankle in an immunocompetent patient.

Mycobacteria, both tuberculous and nontuberculous, are recognized as a cause of chronic bone and joint infection. However, the diagnosis of mycobacterial infection is easily missed because of the absence of systemic involvement. Moreover, specific microbiologic techniques are required to detect mycobacteria in clinical specimens. Infections due to uncommon pathogens such as mycobacteria are more likely to occur in the immunocompromised host. A case of septic arthritis of the ankle and osteomyelitis of the foot due to both tuberculous and nontuberculous mycobacteria in an immunocompetent host is reported here.

Comparative evaluation of oral levofloxacin and parenteral nafcillin in the treatment of experimental methicillin-susceptible Staphylococcus aureus osteomyelitis in rabbits.

Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common pathogen recovered from osteomyelitis patients. The current standard therapeutic method for acute phase osteomyelitis is parenteral antibiotic therapy. However, parenteral administration has negative aspects, such as secondary infection, patient inconvenience and high cost. The use of single oral antibiotic therapy may alleviate these problems. Therefore, the purpose of this study was to compare the effectiveness of standard once per day dosing of oral levofloxacin with a standard parenteral antibiotic regimen (nafcillin four times daily) for the treatment of experimental MSSA osteomyelitis in rabbits. Nearly all tibias from untreated infected controls (n = 27) revealed positive cultures (93%) for S. aureus, while the levofloxacin-treated group (n = 20) demonstrated significantly lower percentages of S. aureus infection (50%). The infected tibias of the nafcillin-treated group (n = 20) demonstrated significantly lower percentages (10%) of infected tibias than either the controls or the levofloxacin-treated groups (P < 0.05). The inferior efficacy of levofloxacin may have been due to the pharmacokinetic profile of this fluoroquinolone. The serum kinetics demonstrated that following single dose administration, levofloxacin was almost undetectable after 12 h. Studies in which levofloxacin is dosed every 12 h or given at increased doses in order to obtain bactericidal concentrations throughout the treatment regimen are needed.

Symptom management in older primary care patients: feasibility of an experimental, written self-disclosure protocol.

BACKGROUND: Distress-driven symptoms are prevalent among older primary care patients and account for a large percentage of office visits and increased medical costs. An experimental written self-disclosure protocol has been shown to reduce symptoms and use of health care services in healthy adults. Written self-disclosure as a method for reducing symptoms has not been evaluated in the primary care setting. OBJECTIVE: To evaluate the feasibility of adapting an experimental written self-disclosure protocol for the primary care setting. DESIGN: Randomized, single-blind feasibility study. SETTING: University-based geriatric and internal medicine primary care clinics. PATIENTS: 45 patients 66 years of age or older without a psychiatric diagnosis. INTERVENTION: Three 20-minute writing sessions focusing on distressing experiences (in the intervention group) or health behaviors (in the control group). MEASUREMENTS: The feasibility outcomes were patient recruitment, protocol logistics, and patient and provider satisfaction. The clinical outcomes were somatic and distress symptoms, health care utilization, and associated costs. RESULTS: One third of patients screened were recruited; 96% of patients recruited completed the protocol. Clinic contact time was an average of 55 minutes per patient. Patients and providers reported high levels of satisfaction with the protocol. Reductions in symptoms were minimal for both groups. Use of outpatient services and associated costs decreased in both groups, but the reduction was twice as great in the treatment group as in the control group. CONCLUSIONS: Findings support the feasibility of implementing the protocol as a primary care intervention.

Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions.

BACKGROUND: The role of bone morphogenetic proteins (BMPs) in osseous repair has been demonstrated in numerous animal models. Recombinant human osteogenic protein-1 (rhOP-1 or BMP-7) has now been produced and was evaluated in a clinical trial conducted under a Food and Drug Administration approved Investigational Device Exemption to establish both the safety and efficacy of this BMP in the treatment of tibial nonunions. The study also compared the clinical and radiographic results with this osteogenic molecule and those achieved with fresh autogenous bone. MATERIALS AND METHODS: One hundred and twenty-two patients (with 124 tibial nonunions) were enrolled in a controlled, prospective, randomized, partially blinded, multi-center clinical trial between February, 1992, and August, 1996, and were followed at frequent intervals over 24 months. Each patient was treated by insertion of an intramedullary rod, accompanied by rhOP-1 in a type I collagen carrier or by fresh bone autograft. Assessment criteria included the severity of pain at the fracture site, the ability to walk with full weight-bearing, the need for surgical re-treatment of the nonunion during the course of this study, plain radiographic evaluation of healing, and physician satisfaction with the clinical course. In addition, adverse events were recorded, and sera were screened for antibodies to OP-1 and type-I collagen at each outpatient visit. RESULTS: At 9 months following the operative procedures (the primary end-point of this study), 81% of the OP-1-treated nonunions (n = 63) and 85% of those receiving autogenous bone (n = 61) were judged by clinical criteria to have been treated successfully (p = 0.524). By radiographic criteria, at this same time point, 75% of those in the OP-1-treated group and 84% of the autograft-treated patients had healed fractures (p = 0.218). These clinical results continued at similar levels of success throughout 2 years of observation, and there was no statistically significant difference in outcome between the two groups of patients at this point (p = 0.939). All patients experienced adverse events. Forty-four percent of patients in each treatment group had serious events, none of which were related to their bone grafts. More than 20% of patients treated with autografts had chronic donor site pain following the procedure. CONCLUSIONS: rhOP-1 (BMP-7), implanted with a type I collagen carrier, was a safe and effective treatment for tibial nonunions. This molecule provided clinical and radiographic results comparable with those achieved with bone autograft, without donor site morbidity.

Binding personal and peripersonal space: evidence from tactile extinction.

Behavioral and neurophysiological studies suggest that the brain constructs different representations of space. Among these representations are personal and peripersonal space. Personal space refers to the space occupied by our bodies. Peripersonal space refers to the space surrounding our bodies, which can be reached by our limbs. How these two representations are bound to give a unified sense of space in which humans act is not clear. We tested 10 patients with tactile extinction to investigate this issue. Tactile extinction is an attentional disorder in which patients are unaware of being touched on their contralesional limb if they are also touched simultaneously on their ipsilesional limb. We hypothesized that mechanisms that bind personal and peripersonal representations would improve these patients' awareness of being touched on their contralesional limbs. Visual--tactile integration and intentional movements were considered candidate mechanisms. Patients were more likely to be aware of contralesional touch when looking towards their contralesional limb than when looking towards their ipsilesional limb, and when actively moving on tactile probes than when receiving tactile stimuli passively. The improved awareness of being touched on the contralesional limb under these conditions suggests that cross-sensory and sensorimotor integration help bind personal and peripersonal space.

Globalization of U.S. health care services: assessment and implementation.

Globalization has become a commonly used term to describe the manner in which organizations in many industries have spread their operations and management to foreign countries. As the trend toward a global economy progresses, more and more industries, including health care, are looking to capitalize on its possible benefits. This article examines globalization in other industries and applies the tools used elsewhere to U.S. health care organizations.

Weighing the evidence for cross over in neglect.

When patients with left-sided neglect are asked to bisect horizontal lines, they tend to place their marks to the right of the line's objective mid-point. However, when asked to bisect short lines they are either more accurate or paradoxically cross over and place their marks to the left of the objective mid-point. Previous explanations of the cross over phenomenon have considered specific aberrations of spatial attention. However, these explanations make no predictions about judgments of non-spatial stimuli. Two patients with right brain damage were asked to judge weights placed on both hands simultaneously. They were biased in reporting weights on the right as being heavier than those on the left. This rightward bias changed with lighter pairs of weights presented in the context of equal reference weights. In one patient the directional bias was eliminated and in the other the bias was reversed so that she was more likely to report the left weight as heavier than the right. These data suggest that a phenomenon analogous to cross over in line bisections also occurs with judgments of non-spatial stimuli. Representations of stimuli appear to be influenced by features of the stimuli encountered on-line and by memory traces of similar stimuli encountered previously. With an attentional deficit, memory traces influence the magnitude of the representation derived on-line disproportionately.

The art and science of chart review.

BACKGROUND: Explicit chart review was an integral part of an ongoing national cooperative project, "Using Achievable Benchmarks of Care to Improve Quality of Care for Outpatients with Depression," conducted by a large managed care organization (MCO) and an academic medical center. Many investigators overlook the complexities involved in obtaining high-quality data. Given a scarcity of advice in the quality improvement (QI) literature on how to conduct chart review, the process of chart review was examined and specific techniques for improving data quality were proposed. METHODS: The abstraction tool was developed and tested in a prepilot phase; perhaps the greatest problem detected was abstractor assumption and interpretation. The need for a clear distinction between symptoms of depression or anxiety and physician diagnosis of major depression or anxiety disorder also became apparent. In designing the variables for the chart review module, four key aspects were considered: classification, format, definition, and presentation. For example, issues in format include use of free-text versus numeric variables, categoric variables, and medication variables (which can be especially challenging for abstraction projects). Quantitative measures of reliability and validity were used to improve and maintain the quality of chart review data. Measuring reliability and validity offers assistance with development of the chart review tool, continuous maintenance of data quality throughout the production phase of chart review, and final documentation of data quality. For projects that require ongoing abstraction of large numbers of clinical records, data quality may be monitored with control charts and the principles of statistical process control. RESULTS: The chart review module, which contained 140 variables, was built using MedQuest software, a suite of tools designed for customized data collection. The overall interrater reliability increased from 80% in the prepilot phase to greater than 96% in the final phase (which included three abstractors and 465 unique charts). The mean time per chart was calculated for each abstractor, and the maximum value was 13.7 +/- 13 minutes. CONCLUSIONS: In general, chart review is more difficult than it appears on the surface. It is also project specific, making a "cookbook" approach difficult. Many factors, such as imprecisely worded research questions, vague specification of variables, poorly designed abstraction tools, inappropriate interpretation by abstractors, and poor or missing recording of data in the chart, may compromise data quality.

Sensory and response interference by ipsilesional stimuli in tactile extinction.

Extinction is thought to be due to a pathologically limited attentional capacity in which multiple stimuli cannot be processed simultaneously to conscious awareness. Patients with tactile extinction are aware of being touched on a contralesional limb, but seem unaware of similar contralesional touch if touched simultaneously on their ipsilesional limb. The ipsilesional stimulus interferes and competes with the processing of the contralesional stimulus. Most theorists assume that the ipsilesional stimulus affects the sensory processing of the contralesional stimulus, although the precise functional level at which this interference occurs is not clear. We report a series of experiments using signal detection analyses to investigate tactile extinction in one patient (DC). These analyses revealed that ipsilesional stimuli, in addition to interfering with processing of contralateral sensations, also interfere with verbal reports of those sensations. This influence on responses suggests that interference in tactile extinction can occur at a post-perceptual level, further 'downstream' than previously thought.

Bone and joint infections in the elderly: practical treatment guidelines.

Two types of haematogenous osteomyelitis that are seen in the elderly are vertebral and long bone osteomyelitis. Osteomyelitis secondary to contiguous foci of infection can occur in older adults without vascular insufficiency (secondary to pressure ulcers) or with vascular insufficiency due to diabetes mellitus or peripheral vascular disease from atherosclerosis. Most cases of osteomyelitis can be reasonably treated with adequate drainage, thorough debridement, obliteration of dead space, wound protection, and antimicrobial therapy. Patients are initially given a broad spectrum antimicrobial that is changed to specific antimicrobial therapy based on meticulous bone cultures taken at debridement surgery or from deep bone biopsies. Surgical management is often required in the treatment of osteomyelitis and includes adequate drainage, extensive debridement of all necrotic tissue, obliteration of dead spaces, stabilisation, adequate soft tissue coverage, and restoration of an effective blood supply. Bone repair and bone mineral density may be significantly retarded and may be corrected by eliminating risk factors, supplementing the diet with calcium, bisphosphonates, and/or vitamin D, and treating with testosterone and/or estrogen when deficient. Sodium fluoride treatment and anabolic steroids may be used as alternatives. Septic arthritis is a medical emergency, and prompt recognition and rapid and aggressive treatment are critical to ensuring a good prognosis. The treatment of septic arthritis includes appropriate antimicrobial therapy and joint drainage. Adverse effects of prescribed antibacterials occur more often in the elderly patient than in young adults. The physician can help to minimise the incidence of adverse effects and improve outcomes by being aware of the principles of clinical pharmacology, the characteristics of specific drugs, and the special physical, psychological and social needs of older patients.

Advanced techniques in foot and ankle reconstruction.

Complex deformities of the foot and ankle remain a difficult problem for even the most experienced surgeon. Many techniques are available to provide correction and no single one is appropriate for all cases. Identical deformities often can be treated with different techniques with equally successful outcomes. Each deformity is unique and the surgeon should be capable of using multiple techniques to provide the most appropriate treatment for the patient and the deformity. Simple deformities often can be handled with simple techniques but more complex problems often require more complex solutions. The techniques discussed here have worked well at the authors' institution but are undergoing constant reevaluation and occasional modification. It is important that the surgeon and the patient understand that with these techniques it is usually possible to provide a functional outcome but never possible to provide a normal foot or ankle. If appropriate goals are set, correction of these challenging deformities can be satisfying to surgeon and patient.

Optimal reporting of health care process measures: inferential statistics as help or hindrance?

In this paper we discuss the appropriate application of inferential statistics to practice profiles and other measures of care. To accomplish our objectives, we first describe the relative merits of measuring three well-recognized domains of medical quality: structure, process, and outcome. Next, we discuss inferential statistics as used in quality improvement. We then describe several common circumstances that arise in the measurement of medical care, giving attention to the application of inferential statistics to each situation. We end with a brief discussion of statistical techniques commonly used in the measurement of quality and challenges that arise with their use.

Orientation bias in unilateral neglect: representational contributions.

Left-neglect patients bisect horizontal lines to the right of true center. Longer lines are bisected further to the right than shorter lines. This line-length effect might be explained by an increase in the rightward bias of attention because longer lines extend further ipsilesionally. Alternatively, neglect patients might be limited in their abilities to internally represent horizontal magnitudes. Patients might orient further rightward with longer lines because these lines have longer representations. If the line-length effect occurs on lines of identical objective length but they are represented differently, then central mechanisms must contribute to the orientation bias. We constructed two types of lines that were perceived by normal subjects as having different lengths, but were of identical extents. Three neglect patients bisected lines perceived as longer, further to the right than lines perceived as shorter. These results demonstrate that relative magnitudes of internal representations contribute to the degree of bias in neglect patients.

Crossmodal and sensorimotor integration in tactile awareness.

We investigated tactile awareness in three patients with tactile extinction of stimuli located on contralesional somatotopic space. Contralesional tactile awareness was enhanced when they gazed to the left and when they moved their limbs. We suggest that personal somatotopic and peripersonal space are integrated by polymodal and sensorimotor links, which allow us to be aware of and act effectively on stimuli in space.

Adult posttraumatic osteomyelitis of the tibia.

Posttraumatic tibial osteomyelitis results from trauma or nosocomial infection from the treatment of trauma that allows organisms to enter bone, proliferate in traumatized tissue, and cause subsequent bone infection. The resulting infection is usually polymicrobial. The patient may be classified using the May and the Cierny-Mader classification systems. The diagnosis is based on the isolation of the pathogen(s) from the bone, or blood cultures. Appropriate therapy of posttraumatic tibial osteomyelitis includes adequate drainage, thorough debridement, obliteration of dead space, stabilization when necessary, wound protection, and specific antimicrobial therapy.

Antimicrobial treatment of chronic osteomyelitis.

Chronic osteomyelitis has been a difficult problem for patients and the treating physicians. Appropriate antibiotic therapy is necessary to arrest osteomyelitis along with adequate surgical therapy. Factors involved in choosing the appropriate antibiotic(s) include infection type, infecting organism, sensitivity results, host factors, and antibiotic characteristics. Initially, antibiotics are chosen on the basis of the organisms that are suspected to be causing the infection. Once the infecting organism(s) is isolated and sensitivities are established, the initial antibiotic(s) may be modified. In selecting specific antibiotics for the treatment of osteomyelitis, the type of infection, current hospital sensitivity resistance patterns, and the risk of adverse reactions must be strongly appraised. Antibiotic classes used in the treatment of osteomyelitis include penicillins, beta-lactamase inhibitors, cephalosporins, other beta-lactams (aztreonam and imipenem), vancomycin, clindamycin, rifampin, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, metronidazole, and new investigational agents including teicoplanin, quinupristin/dalfopristin, and oxazolidinones. Traditional treatments have used operative procedures followed by 4 to 6 weeks of parenteral antibiotics. Adjunctive therapy for treating chronic osteomyelitis may be achieved by using beads, spacers, or coated implants to deliver local antibiotic therapy and/or by using hyperbaric oxygen therapy (once per day for 90-120 minutes at two to three atmospheres at 100% oxygen).