Heidi Israel

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freunds caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

Timing of Wound Closure in Open Fractures Based on Cultures Obtained After Debridement

BACKGROUND The timing of wound closure in open fractures has remained an inexact science. Numerous recommendations have been made for the management of these injuries regarding the optimal time to perform competent wound closure, with all advice based on subjective parameters. The purpose of this study was to determine the utility of a prospective protocol with use of wound cultures obtained after irrigation and debridement as a guide to the timing of wound closure following an open fracture of an extremity. METHODS Four hundred and twenty-two open fractures had emergency irrigation and debridement, fracture stabilization, and open wound management. Wound cultures were obtained for aerobic and anaerobic analysis following debridement. At forty-eight hours after debridement, patients were again returned to surgery. If the initial culture results were positive, a repeat irrigation and debridement was carried out, and additional cultures were obtained after debridement. This procedure was repeated, and the wound was not closed until negative culture results were achieved. RESULTS Of the 422 open fractures, 346 were available for long-term follow-up. The overall deep infection rate was 4.3%. Gustilo Type-II fractures had a deep infection rate of 4%, and Type-III fractures had an infection rate of 5.7%. Type-III fractures demonstrated differences among the fracture patterns within this type, as infection developed in 1.8% of Type-IIIA injuries, 10.6% of Type-IIIB fractures, and 20% of Type-IIIC fractures. Fractures requiring multiple debridement procedures and those in patients with diabetes or an increased body mass index demonstrated higher rates of infection. With the numbers studied, fractures in which the wound was closed in the presence of positive cultures (a protocol breach) did not have a significantly increased risk of deep infection (p = 0.0501). CONCLUSIONS The use of this standardized protocol was shown to achieve a very low rate of deep infection compared with historical controls. An increased number of irrigation and debridement procedures are required to achieve this improved outcome. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

Computed tomography as a predictor of hip stability status in posterior wall fractures of the acetabulum.

Objectives: Studies using 2-dimensional computed tomography-derived criteria indicate that, in general, posterior wall fractures involving less than 20% of the posterior wall are stable and able to withstand physiologic loads, whereas those involving greater than 40%-50% are unstable, leaving a wide range of posterior wall fractures classified as indeterminate. The purpose of this study was to assess the ability of static measurement of posterior acetabular wall fragment size using computed tomography to predict hip stability status, as determined by dynamic stress examination under anesthesia. Design: Diagnostic level I. Retrospective analysis with testing of previously developed diagnostic criteria in a series of consecutive patients (with universally applied reference “gold” standard). Setting: Level I trauma center. Patients: Thirty-three consecutive patients with isolated unilateral posterior wall (OTA 62-A1) acetabular fractures were evaluated by dynamic fluoroscopic stress testing under general anesthesia (examination under anesthesia) to determine hip stability status and subsequent clinical treatment. Intervention: Three methods were used in a blinded fashion to calculate posterior wall fracture fragment size using 2-dimensional computed tomograms. These methods include those previously described by Calkins et al, which measures the smallest amount of intact acetabular arc, and Keith et al, which measures fragment size at the level of the fovea, and an alternative modification of that of Keith et al using the level of largest posterior wall deficit. Each method classifies hip instability into 3 groups: (1) stable, (2) indeterminate, and (3) unstable. The examination under anesthesia served as the gold standard. Main Outcome Measurement: Examination under anesthesia Results: Examination under anesthesia determined 15 hips to be unstable and 18 hips to be stable. The analyses showed that the methods of Calkins et al and Keith et al had a substantial percentage of incorrect predictions, especially in the critical group 1 patients (those predicted to be stable but were actually unstable). The percent incorrectly predicted for these group 1 patients was 33.3% (positive predictive value 66.7%) for the data derived form Calkins et al and 14.3% (positive predictive value 85.7%) for the data derived form Keith et al. In contradistinction, for the alternative method, specificity, sensitivity, and positive predictive value were all 100% with a 0% incorrectly predicted. However, with this alternative method, there was an increase in the number of group 2 fractures (23), as compared with the group 2 numbers for Calkins et al (n = 7) and Keith et al (n = 18). Reanalysis of the data for better potential cut points indicated that none of the methods could be improved in this way. Conclusions: The alternative method is the only reliable technique that is predictive of hip stability for small fracture fragments while also being predictive of instability for large fracture fragments. However, these findings are based on small patient numbers, and there remain a substantial number of fractures involving 20% or more of the posterior wall that are both stable and unstable by examination under anesthesia. Therefore, given the low risk of the stress examination and the inherent problems making the computed tomography measurements, dynamic fluoroscopic stress testing under general anesthesia should be the preferred method for the determination of hip stability status after posterior wall fractures of the acetabulum.

Community opinions in the management of corneal ulcers and ophthalmic antibiotics: a survey of 4 states.

Objective: To evaluate the ophthalmic communitys current opinions of the management of bacterial keratitis and usage of the currently available ophthalmic antibiotics. Methods: An anonymous questionnaire was mailed to ophthalmologists in California, Florida, Illinois, and Missouri. The results were tabulated and analyzed statistically. Results: Six hundred twenty-nine usable questionnaires (10.3%) were returned. In the management of corneal ulcers, 42.2% of comprehensive ophthalmologists and 75.3% of cornea specialists perform Gram stains some of the time. A total of 73.3% of comprehensive ophthalmologists and 93.7% of cornea specialists perform corneal cultures some of the time. A total of 88.8% of comprehensive ophthalmologists and 76% of cornea specialists initiate treatment with the newer fluoroquinolone antibiotics. A total of 12.1% of comprehensive ophthalmologists and 41% of cornea specialists would select fortified antibiotics for the treatment of corneal ulcers. The percentage of those who feel that fortified antibiotics are superior ranges from 17.7% for comprehensive ophthalmologists to 33.3% for cornea specialists. A total of 65.7% of comprehensive ophthalmologists indicate that the newer fluoroquinolones have impacted their practices, and 58.3% indicate that they represent an improvement over older fluoroquinolones. Conclusions: Most responding ophthalmologists initiate empiric therapy with the newer fluoroquinolone antibiotics for corneal ulcers, forgoing Gram staining and culturing. However, respondents are not universally sanguine about the newer fluoroquinolones. The practice patterns and opinions on antibiotics differ almost universally between comprehensive ophthalmologists and cornea specialists. Larger, more detailed surveys and more specific analyses would help to further establish the factors that lead to differing management choices and opinions.

A biomechanical comparison of one-third tubular plates versus periarticular plates for fixation of osteoporotic distal fibula fractures.

Objectives: The purpose of this study was to test the biomechanical properties of locking and nonlocking plates using one-third tubular and periarticular plate designs in an osteoporotic distal fibula fracture model. Methods: Twenty-four cadaveric specimens, whose bone mineral densities were obtained using dual x-ray absorptiometry scans, were tested. The fracture model simulated an OTA 44-B2.1 fracture. The constructs included (1) nonlocking one-third tubular plate, (2) locking one-third tubular plate, (3) nonlocking periarticular plate, and (4) locking periarticular plate. The specimens underwent axial loading followed by torsional loading to failure. Statistical analysis was performed using Kruskal–Wallis testing and further analysis with Mann–Whitney testing. Results: The periarticular plates had greater rotational stiffness compared with the one-third tubular plates (P = 0.04). The nonlocking plates had greater torque to failure than the locking plates (P = 0.01). The nonlocking one-third tubular plate had greater torque to failure than the locking one-third tubular plate (P = 0.03). No significant differences were found in any of the comparisons regarding axial stiffness. Conclusions: In biomechanical testing using an osteoporotic model of OTA 44-B2.1 fractures, periarticular plates were superior to one-third tubular plates in rotational stiffness only. Locking plates did not outperform their nonlocking counterparts. Periarticular plates should be considered when treating osteoporotic distal fibula fractures, but one-third tubular plates and nonlocking plates provide adequate fixation for these injuries.

Locked plating of comminuted distal femur fractures: does unlocked screw placement affect stability and failure?

Objectives: Locked plates provide greater stiffness, possibly at the expense of fracture healing. The purpose of this study is to evaluate construct stiffness of distal femur plates as a function of unlocked screw position in cadaveric distal femur fractures. Methods: Osteoporotic cadaveric femurs were used. Four diaphyseal bridge plate constructs were created using 13-hole distal femur locking plates, all with identical condylar fixation. Constructs included all locked (AL), all unlocked (AUL), proximal unlocked (PUL), and distally unlocked (DUL) groups. Constructs underwent cyclic axial loading with increasing force per interval. Data were gathered on axial stiffness, torsional stiffness, maximum torque required for 5-degree external rotation, and axial force to failure. Results: Twenty-one specimens were divided into AL, AUL, PUL, and DUL groups. Axial stiffness was not significantly different between the constructs. AL and PUL demonstrated greater torsional stiffness, maximum torque, and force to failure than AUL and AL showed greater final torsional stiffness and failure force than DUL (P < 0.05). AL and PUL had similar axial, torsion, and failure measures, as did AUL and DUL constructs. All but 2 specimens fractured before medial gap closure during failure tests. Drop-offs on load–displacement curves confirmed all failures. Conclusions: Only the screw nearest the gap had significant effect on torsional and failure stiffness but not axial stiffness. Construct mechanics depended on the type of screw placed in this position. This screw nearest the fracture dictates working length stiffness when the working length itself is constant and in turn determines overall construct stiffness in osteoporotic bone.

Relationship of cortical thickness of the proximal humerus and pullout strength of a locked plate and screw construct.

Background: No study to date has evaluated cortical thickness as it relates to locking plate failure or screw pullout in the proximal humerus. The purpose of this study is to determine the relationship between proximal humerus cortical thickness and locked plate hardware failure in a cadaveric proximal humerus fracture model. Methods: Twelve humerus specimens were placed into two groups based on the proximal humerus cortical thickness on an anteroposterior radiograph: less than 4 mm and greater than 4 mm. The specimens were plated with a six-hole proximal humerus locking plate and a 15-mm resection osteotomy at the surgical neck was performed. The specimens were tested in a materials testing machine at a displacement of 5 mm/min to failure. Results: Load at failure, stiffness, maximum load, failure, and fracture gap closure were all statistically similar (P > 0.05) between the groups. Conclusion: Our biomechanical study used modern locked plate–screw construct fixation of a simulated two-part proximal humerus fracture. The mechanical strength was unaffected based on a threshold combined proximal humerus cortical thickness of 4 mm.

Is the Marx Activity Scale Reliable in Patients Younger Than 18 Years

Background: There is no baseline activity scale yet validated in pediatric patients. The Marx and Tegner scales have been validated in adult patients only. The Tegner scale involves questions not pertinent to children, such as their work activity. The Marx scale is simple, and all its questions can be related to athletic activities. Hypothesis: The Marx scale is reliable for use in a pediatric population. Study Design: Cohort study. Level of Evidence: Level 2. Methods: Patients younger than 18 years were given the Marx activity scale in clinic and again 3 weeks later. The patients were divided into 3 groups, of at least 50 patients each, based on presenting diagnosis: knee injury, lower extremity (non-knee) injury, and upper extremity injury. Test-retest reliability was determined for the overall scores and the individual questions. Differences in scores were also compared based on age (<14 vs ≥14 years). Results: A total of 162 patients (mean age, 14.4 years; range, 8-17 years) were included. The Marx scale had a high intraclass correlation coefficient (ICC) overall as well as for each of its 4 questions. Both older and younger patients had ICCs >0.80, though the older group generally had higher scores. The mean score was 13.55 (out of 16), and 50.6% scored the maximum; only 1.9% scored the minimum. Mean scores for the knee, lower extremity, and upper extremity groups were 13.71 (SD, 3.70), 13.22 (SD, 4.18), and 13.68 (SD, 3.33), respectively (P > 0.05). There also was no difference in total score based on age (P = 0.88). Conclusion: The Marx activity scale is reliable in patients younger than 18 years with injuries to the knee and lower extremities, though the scale was less reliable in patients younger than 14 years. There is a significant ceiling effect present, which limits its overall usefulness. Clinical Relevance: Although there is no other current substitute, the Marx activity scale is not an ideal measurement of younger patients’ baseline activity levels.

Attitudes toward Retirement of Ophthalmology Department Chairs

PURPOSE To identify common perceptions and ideas about preparation and planning for retirement of chairs of academic departments of ophthalmology, determining areas of particular stress and proposing ways to better prepare for retirement. DESIGN Cross-sectional study. PARTICIPANTS One-hundred sixteen chairs of academic departments of ophthalmology in the United States. METHODS A confidential online survey emailed to ophthalmology chairs. MAIN OUTCOME MEASURES Surveys assessed demographics; current work schedule; perceptions, preparation, and planning for retirement; and retirement training for faculty and residents. RESULTS Ninety-six department chairs responded to the survey (82% response rate). Most chairs anticipate retiring around age 70. Significantly, only 9% are looking forward to retirement. Reasons for delaying retirement include keeping active (37%), income/insurance/benefits (20%), and maintaining lifestyle (17%). The most common concern is financing retirement (46%). Forty percent anticipate their reason for retirement will be because of age or health, whereas 20% anticipate fatigue or burnout. Nearly half of the respondents have no specific plan upon retirement. Most respondents anticipate pursuing other interests (43%); 32% intend to spend time with family, vacationing, and travelling. Younger respondents are more concerned with the financial aspects of retirement while more senior respondents appear to delay retirement to keep active or because they enjoy their work. CONCLUSIONS Retirement is a source of stress for many ophthalmology department chairs and many indicate financial preparation is their major concern. Despite this, the major reason for putting off retirement is a desire to keep active. Developing a retirement plan eases stress and engenders a feeling of confidence about the future.

The aging motorcyclist: a comparative epidemiologic study on pattern and severity of injury.

BACKGROUND The industry statistics demonstrates an increasingly older population is riding motorcycles. This study was designed to identify the orthopedic injuries and their hospital outcome for riders older than 50 years versus younger than 50 years. METHODS We identified all patients who were injured in a motorcycle collision between 2004 and 2009. The charts were reviewed to obtain demographic data, initial injury severity markers, and hospital outcome measures. Radiographs were reviewed and all fractures classified according to the AO/OTA system. Statistical analysis was completed with patients grouped into age <50 years versus ≥50 years with p ⩽ 0.05 determined as significant. RESULTS There were 436 patients who comprised the study population. Older patients had more medical comorbidities at the time of injury (p < 0.001). There was no significant difference between age groups for any initial injury severity markers or fracture complexity. Older patients had a longer average length of stay (p < 0.05), intensive care unit days (p < 0.001), ventilator days (p = 0.001), and rate of complications than younger patients (p < 0.05). Older patients had a significantly higher mortality rate (6.8% vs. 2.4%; p = 0.04). CONCLUSIONS Advanced age demonstrated correlation with prolonged hospital stay and requirement of more aggressive medical care. An increased risk of mortality was demonstrated for the older motorcyclist. However, age alone did not affect the severity or distribution of orthopedic injuries in this study. As the motorcycle riding population ages, it is important to understand the injuries and hospital course of these patients, along with the increased mortality rates and health care expenditure burden which can be expected. (J Trauma. 2012;XX: 000–000. Copyright