Validation of the PLASMIC score at a University Medical Center.

BACKGROUND: The PLASMIC score was recently described as a convenient tool for predicting ADAMTS13 activity ≤10% in patients with possible thrombotic thrombocytopenic purpura (TTP), while awaiting the results of this send-out test. The purpose of this study was to validate the PLASMIC score at our University Medical Center. METHODS: Apheresis records were reviewed from 2008 to 2017 to identify patients who received plasma exchange (PLEX) for suspected TTP. The ADAMTS13 activity and PLASMIC scoring criteria were recorded, and the PLASMIC score was calculated. RESULTS: Of the 41 patients identified, 20 met inclusion criteria, of which 7 patients had ADAMTS13 activity ≤10%. Intermediate and high PLASMIC scores had 100% sensitivity, 46.2% specificity, 50% positive predictive value (PPV), and 100% negative predictive value (NPV). CONCLUSION: These results are consistent with the original validation study of the PLASMIC score, supporting the efficacy of the PLASMIC score and validating its use at our institution.

The Fear of Alzheimer's Disease Scale: a new measure designed to assess anticipatory dementia in older adults.

BACKGROUND: As the prevalence of Alzheimer's disease (AD) is rapidly increasing, apprehension about developing the degenerative disease (anticipatory dementia or fear of developing AD) has become a topic of interest. However, most studies of anticipatory dementia have utilized brief, nonvalidated measures to explore older adults' apprehension. As such, there is a significant need for a psychometrically sound instrument to measure this fear. METHODS: The current study utilized 101 older adults ages 65 to 91 to develop and validate an important new scale, the Fear of Alzheimer's Disease Scale (FADS). Construct validity of the FADS was assessed with the State-Trait Anxiety Inventory-Form Y (STAI-Y). RESULTS: Analyses revealed a three-factor model for the FADS (i.e., General Fear, Physical Symptoms, and Catastrophic Attitude) and an α of 0.94 for the entire measure, indicating good internal consistency. The FADS demonstrated good construct validity, as it was significantly correlated with both the state and trait subscales of the STAI-Y, with the trait subscale yielding the highest correlation. CONCLUSION: The FADS is a reliable and valid instrument and is the first of its kind available to directly address anticipatory dementia among a general population of older adults.

Effect of femoral component design on patellofemoral crepitance and patella clunk syndrome after posterior-stabilized total knee arthroplasty.

The purpose of this study was to determine if recent changes to the femoral component of a particular posterior-stabilized total knee prosthesis would affect the incidence of postoperative patellofemoral crepitance and patella clunk syndrome. One hundred eight total knee arthroplasties were performed with the conventional design; 136 were performed after the femoral component was changed. Complications were compared between the groups with an average follow-up of 17.7 months and 12.4 months, respectively. Thirteen knees with the conventional design (12%) were found to have patellofemoral complications; no complications were noted with the new design (P < .0001). Femoral components with a deep trochlear groove and smooth transition of the intercondylar box appear to better accommodate any peripatellar fibrous nodule that may form after total knee arthroplasty.

Measuring mixed cellulose ester (MCE) filter mass under variable humidity conditions.

Mixed cellulose ester (MCE) filters, used routinely to collect dust samples from air for fiber analysis, are the only filter type that can be prepared for both phased contrast microscopy and transmission electron microscopy analyses. However, whenever fiber counts require collecting dust masses <100 µg on a single filter under variable relative humidity (RH) conditions, historically noted effects of humidity on MCE filter mass can hinder accurate estimates of dust mass, measured as loaded minus unloaded filter mass (M). In this study, a baseline set of hundreds of paired measures of change in RH versus M over different time intervals were obtained over a 5-day period for replicate series of 40 unloaded 37-mm MCE filters under varying RH conditions at a nearly constant temperature. Similar baseline data were obtained for 25-mm MCE filters. Linear regressions fit to these data allow improved estimates of dust mass loaded onto MCE filters from measures of M and RH made before and after loading occurs. Using established theory, these relationships were generalized to address temperature variation as well, and examples of numerical applications are provided.

Simulation tests to assess occupational exposure to airborne asbestos from artificially weathered asphalt-based roofing products.

Historically, asbestos-containing roof cements and coatings were widely used for patching and repairing leaks. Although fiber releases from these materials when newly applied have been studied, there are virtually no useful data on airborne asbestos fiber concentrations associated with the repair or removal of weathered roof coatings and cements, as most studies involve complete tear-out of old roofs, rather than only limited removal of the roof coating or cement during a repair job. This study was undertaken to estimate potential chrysotile asbestos fiber exposures specific to these types of roofing products following artificially enhanced weathering. Roof panels coated with plastic roof cement and fibered roof coating were subjected to intense solar radiation and daily simulated precipitation events for 1 year and then scraped to remove the weathered materials to assess chrysotile fiber release and potential worker exposures. Analysis of measured fiber concentrations for hand scraping of the weathered products showed 8-h time-weighted average concentrations that were well below the current Occupational Safety and Health Administration permissible exposure limit for asbestos. There was, however, visibly more dust and a few more fibers collected during the hand scraping of weathered products compared to the cured products previously tested. There was a notable difference between fibers released from weathered and cured roofing products. In weathered samples, a large fraction of chrysotile fibers contained low concentrations of or essentially no magnesium and did not meet the spectral, mineralogical, or morphological definitions of chrysotile asbestos. The extent of magnesium leaching from chrysotile fibers is of interest because several researchers have reported that magnesium-depleted chrysotile fibers are less toxic and produce fewer mesothelial tumors in animal studies than normal chrysotile fibers.

A small molecule-kinase interaction map for clinical kinase inhibitors.

Kinase inhibitors show great promise as a new class of therapeutics. Here we describe an efficient way to determine kinase inhibitor specificity by measuring binding of small molecules to the ATP site of kinases. We have profiled 20 kinase inhibitors, including 16 that are approved drugs or in clinical development, against a panel of 119 protein kinases. We find that specificity varies widely and is not strongly correlated with chemical structure or the identity of the intended target. Many novel interactions were identified, including tight binding of the p38 inhibitor BIRB-796 to an imatinib-resistant variant of the ABL kinase, and binding of imatinib to the SRC-family kinase LCK. We also show that mutations in the epidermal growth factor receptor (EGFR) found in gefitinib-responsive patients do not affect the binding affinity of gefitinib or erlotinib. Our results represent a systematic small molecule-protein interaction map for clinical compounds across a large number of related proteins.

Two-year follow-up of bibliotherapy and individual cognitive therapy for depressed older adults.

This study examined the stability of treatment gains after receiving either cognitive bibliotherapy or individual cognitive psychotherapy for depression in older adults. A 2-year follow-up of 23 participants from Floyd, Scogin, McKendree-Smith, Floyd, and Rokke (2004) was conducted by comparing pre-and posttreatment scores with follow-up scores on the Hamilton Rating Scale for Depression (HRSD) and the Geriatric Depression Scale (GDS). Results indicated that treatment gains from baseline to the 2-year follow-up period were maintained on the HRSD and GDS, and there was not a significant decline from posttreatment to follow-up. There were no significant differences between the treatments on the GDS or HRSD at the 2-year follow-up; however, bibliotherapy participants had significantly more recurrences of depression during the follow-up period.

Two-year follow-up of self-examination therapy for generalized anxiety disorder.

This study examined the stability of treatment gains after receiving self-examination therapy (SET) [Bowman, D. (1995). Innovations in clinical practice: a source book. Professional Resource Press.] for generalized anxiety disorder. A 2-year follow-up of 16 participants from Bowman, Scogin, Floyd, Patton, and Gist [J. Counsel. Psychol. 44 (1997) 267] was conducted by comparing pre- and post-treatment measures with follow-up measures from the Hamilton Anxiety Rating Scale-Revised (HARS-R), the State-Trait Anxiety Inventory (STAI), and the SET quiz. Results indicated treatment gains from baseline to the 2-year follow-up period were maintained on all measures, and there was not a significant decline from post-treatment to follow-up on the HARS-R and STAI. These results suggest that SET for treatment of generalized anxiety disorder (GAD) may be effective in both the immediate and long-term reduction of GAD symptoms.

Cognitive therapy for depression: a comparison of individual psychotherapy and bibliotherapy for depressed older adults.

Thirty-one community-residing older adults age 60 or over either received 16 sessions of individual cognitive psychotherapy (Beck, Rush, Shaw, & Emery, 1979) or read Feeling Good (Bums, 1980) for bibliotherapy. Posttreatment comparisons with the delayed-treatment control indicated that both treatments were superior to a delayed-treatment control. Individual psychotherapy was superior to bibliotherapy at posttreatment on self-reported depression, but there were no differences on clinician-rated depression. Further, bibliotherapy participants continued to improve after posttreatment. and there were no differences between treatments at 3-month follow-up. Results suggest that bibliotherapy and that individual psychotherapy are both viable treatment options for depression in older adults.

Early experience with the proximal femoral locking plate.

The purpose of this study was to evaluate the failure rate of proximal femoral locking plates after an initial 2 years of use at a Level I trauma center. This retrospective chart review included 13 patients with intertrochanteric or peritrochanteric femoral fractures who underwent open reduction and internal fixation. Average patient age was 47 years (range, 23-80 years); average follow-up was 12.7 months (range, 2 weeks to 23 months). Three (23%) patients experienced catastrophic failure of the implant. The overall revision rate was 46% (6 of 13). One patient experienced avascular necrosis and required a planned total hip arthroplasty. In the appropriate setting, the proximal femoral locking plate can offer stable fixation for fractures involving the proximal femur; however, this series highlights the difficulties associated with treating these injuries, especially in patients with multiple injuries. Care must be taken to avoid varus malalignment and to address metabolic bone dysfunction.

Pseudoseptic arthritis of the shoulder following pneumococcal vaccination.

Pseudoseptic arthritis is primarily described in rheumatoid arthritis and other systemic inflammatory conditions. To our knowledge, only 1 case report of pseudoseptic arthritis associated with intra-articular injection of a pneumococcal polyvalent vaccine (PPV) has been published. Here, a second case is presented in which a patient presented with swelling, pain, and erythema of the affected shoulder. A 59-year-old woman presented to the emergency department with a 3-day history of severe pain and decreased mobility of her left shoulder after receiving a PPV vaccination. Her clinical and laboratory workup was suspicious for septic arthritis; however, magnetic resonance imaging of the affected shoulder with and without contrast showed only a partial thickness tear of the rotator cuff, fluid in the subacromial/subdeltoid bursa, and subcutaneous edema without evidence of an abscess. Based on the clinical and laboratory data, she underwent arthroscopic debridement. There was inflammatory tissue throughout the shoulder but no obvious purulent material. She did well postoperatively with a supervised range of motion rehabilitation protocol. Her cultures remained negative. At 12 weeks, she was discharged from follow-up. We suspect that the vaccination was inadvertently injected into the glenohumeral joint directly through the rotator cuff given the lack of a full-thickness tear and the patient's thin body habitus, which could explain her aseptic inflammatory arthritis.

Why do medical students choose orthopaedics as a career?

BACKGROUND: The primary influence on medical students' career choice is their third-year clerkship. However, orthopaedics is not a required rotation in the curriculum of most medical schools. Our goals were to identify factors that motivate students to choose an orthopaedic career and to compare these with the factors that influence students to choose nonorthopaedic disciplines. METHODS: Fourth-year medical students and orthopaedic residents at the postgraduate year (PGY)-1 level at eight orthopaedic training programs in the United States were surveyed to determine the reasons that they chose orthopaedics instead of other medical or surgical fields. RESULTS: Of the 622 individuals who responded to our survey, 125 were entering orthopaedics and 497 were not. Although career choice in both groups was most heavily influenced by third and fourth-year clinical rotations and faculty contacts, orthopaedics-bound respondents were more likely than non-orthopaedics-bound respondents to be strongly influenced by experiences and people prior to medical school. Orthopaedics-bound respondents were less likely to report a faculty member as the most important person influencing career choice. Fifty-one percent (sixty-three) of 124 students who selected orthopaedics had already decided to pursue this field prior to their third-year rotation. Patient care was chosen by 71% (347) of 490 non-orthopaedics-bound respondents and 75% (ninety-four) of 125 orthopaedics-bound respondents as the most important factor for pursuing a particular field. Income was not selected as the deciding factor by respondents in either group. CONCLUSIONS: Although faculty contacts and third-year clinical rotations played an important role in student selection of specialty training, they were less influential for those choosing an orthopaedic career than for those choosing other disciplines. Many students choosing orthopaedics made this decision prior to medical school. We believe that increased exposure to positive clinical role models and experiences during medical school would enhance medical students' options for choosing orthopaedic surgery as a career. Anticipated income did not play a deciding role in career selection.

Outcome of nonoperative vs operative treatment of humeral shaft fractures: a retrospective study of 213 patients.

Standard treatment for most humeral shaft fractures is nonoperative functional bracing; however, certain clinical scenarios necessitate operative intervention. There have been few studies in the literature comparing nonoperative and operative fixation of humeral shaft fractures. Two-hundred thirteen adult patients with a humeral shaft fracture who satisfied inclusion criteria were treated at 2 level 1 trauma centers with either a functional brace (nonoperative treatment group) or compression plating (operative treatment group). Main outcome measures were evaluated retrospectively and included time to union, nonunion, malunion, infection, incidence of radial nerve palsy, and elbow range of motion (ROM). The occurrence of nonunion (20.6% vs 8.7%; P=.0128) and malunion (12.7% vs 1.3%; P=.0011) was statistically significant and more common in the nonoperative group. There was no significant difference in infection rate between nonoperative and operative treatment (3.2% vs 4.7%; P=1.0000). Radial nerve palsy presented after fracture treatment in 9.5% of patients in the nonoperative group and in 2.7% of patients managed operatively (P=.0678). No difference in time to union or ultimate ROM was found between the 2 groups. Closed treatment of humerus fractures had a significantly higher rate of nonunion and malunion while operative intervention demonstrated no significant differences in time to union, infection, or iatrogenic radial nerve palsy. Nonoperative management has historically been the treatment of choice for many humeral shaft fractures, however, in certain clinical scenarios these fractures may be well served by compression plating.

Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.

Interactions between kinases and small molecule inhibitors can be activation state dependent. A detailed understanding of inhibitor binding therefore requires characterizing interactions across multiple activation states. We have systematically explored the effects of ABL1 activation loop phosphorylation and PDGFR family autoinhibitory juxtamembrane domain docking on inhibitor binding affinity. For a diverse compound set, the affinity patterns correctly classify inhibitors as having type I or type II binding modes, and we show that juxtamembrane domain docking can have dramatic negative effects on inhibitor affinity. The results have allowed us to associate ligand-induced conformational changes observed in cocrystal structures with specific energetic costs. The approach we describe enables investigation of the complex relationship between kinase activation state and compound binding affinity and should facilitate strategic inhibitor design.

A quantitative analysis of kinase inhibitor selectivity.

Kinase inhibitors are a new class of therapeutics with a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined, and an important step toward understanding the relationship between selectivity, efficacy and safety is the exploration of how inhibitors interact with the human kinome. We present interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome. The data constitute the most comprehensive study of kinase inhibitor selectivity to date and reveal a wide diversity of interaction patterns. To enable a global analysis of the results, we introduce the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns. We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity.

The existential effects of traumatic experiences: a survey of young adults.

This study examined the relation between exposure to trauma and attitudes toward existential issues. Participants were 504 undergraduate students (average age = 19.67) who answered questions on exposure to trauma, fear of death, overall distress, and meaning in life. Results indicated that those with a history of trauma exposure had higher levels of overall distress, but there were no differences in death anxiety or meaning in life. The results suggest that the positive outcomes (less fear of death and increased meaning in life) associated with exposure to traumatic events may be relatively rare, especially amongst younger adults.

Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases.

To realize the full potential of targeted protein kinase inhibitors for the treatment of cancer, it is important to address the emergence of drug resistance in treated patients. Mutant forms of BCR-ABL, KIT, and the EGF receptor (EGFR) have been found that confer resistance to the drugs imatinib, gefitinib, and erlotinib. The mutations weaken or prevent drug binding, and interestingly, one of the most common sites of mutation in all three kinases is a highly conserved "gatekeeper" threonine residue near the kinase active site. We have identified existing clinical compounds that bind and inhibit drug-resistant mutant variants of ABL, KIT, and EGFR. We found that the Aurora kinase inhibitor VX-680 and the p38 inhibitor BIRB-796 inhibit the imatinib- and BMS-354825-resistant ABL(T315I) kinase. The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. EKB-569 and CI-1033 are already in clinical trials, and our results suggest that they should be considered for testing in the treatment of gefitinib/erlotinib-resistant non-small cell lung cancer. The results highlight the strategy of screening existing clinical compounds against newly identified drug-resistant mutant variants to find compounds that may serve as starting points for the development of next-generation drugs, or that could be used directly to treat patients that have acquired resistance to first-generation targeted therapy.

Bibliotherapy as an adjunct to psychotherapy for depression in older adults.

Bibliotherapy, reading a self-help book for the treatment of psychological problems, has been shown to be effective as a "stand-alone" treatment for depression. Many practitioners recommend self-help books as an adjunct to treatment. This article offers some guidelines for the use of bibliotherapy as an adjunct to individual psychotherapy with depressed older adults. Two clinical cases demonstrate how bibliotherapy can be used effectively in conjunction with individual psychotherapy.