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The purpose of this study was to compare the bacteriologic and clinical efficacy of oral cephalexin twice vs. three times daily vs. cefadroxil once daily as therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. A prospective open-label, observational cohort study was conducted over 18 months (January 2000-June 2001). Children enrolled had an acute onset of symptoms and signs of a tonsillopharyngeal illness and a laboratory-documented GABHS infection. Follow-up examination and laboratory testing occurred 21 +/- 4 days following enrollment. Two hundred seventy-one patients were enrolled (intent to treat group): 63 received cephalexin twice daily, 124 received cephalexin three times daily, and 84 received cefadroxil once daily. Fifty-three children did not return for the follow-up visit, leaving 218 patients in the per-protocol group: 54 cephalexin twice-daily treated, 94 cephalexin 3-times daily treated, and 70 cefadroxil once-daily treated. In the per-protocol group, bacteriologic cure for those treated with cephalexin twice daily was 87%, for cephalexin 3 times daily, it was 81% and for cefadroxil once daily it was 81% (p = 0.61). The clinical cure rate for cephalexin twice-daily treatment was 91%; for three-times daily, it was 86%; and for cefadroxil once daily, it was 84% (p = 0.56). Because treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences. Younger age of patient was significantly associated with bacteriologic (p = 0.04) and clinical (p = 0.01) failure independent of treatment group but in the adjusted logistic model no differences were found among the 3 treatment regimens. Cephalexin dosed twice daily or three times daily and cefadroxil dosed once daily appear equivalent in bacteriologic and clinical cure of GABHS tonsillopharyngitis. [ABSTRACT FROM AUTHOR]

Rationale: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among individuals with chronic obstructive pulmonary disease (COPD). Black women with COPD are at elevated risk of CVD-related mortality compared with White women. CVD risk factors are undertreated in Black men and women. However, barriers to CVD prevention from the perspective of Black individuals living with COPD have not been previously identified. Objectives: To identify barriers and facilitators for CVD prevention among Black individuals living with COPD. Methods: We conducted semistructured interviews with Black participants living with COPD and attending clinics at two urban hospitals. Participants were included if they had physician-confirmed COPD diagnoses and presence of CVD or CVD risk factors. Interviews were conducted until thematic saturation was reached, with additional interviews conducted to confirm saturation. Data were analyzed using thematic analysis, iteratively revising and updating the codebook by consensus of the study team. Codes were grouped into categories, subthemes, and themes. Themes were organized using the social ecological framework into individual, interpersonal, health system, and societal levels. Results: We interviewed 30 participants of mean age 67.8 ± 8.3 years; 17 (57%) were Black women and 13 (43%) were Black men. Individual-level themes were that living with COPD and resultant multimorbidity affects CVD prevention (theme 1) and that self-efficacy and advocacy affect care received (theme 2). At the interpersonal level, supportive relationships facilitate improved access to CVD prevention (theme 3). System-level themes were that health systems are not designed to support patients with COPD and CVD (theme 4) and that health systems do not deliver effective patient education (theme 5). At the societal level, structural barriers and racism prevent access to care and adoption of a healthy lifestyle (theme 6). Conclusions: We identified barriers to CVD prevention at all levels of the socioecological framework for Black individuals living with COPD. To maximize their impact, future interventions to prevent CVD among individuals with COPD can use these findings to target barriers at multiple levels.

Background: Alcohol and other substance use disorders usually begin with substance use in adolescence. Pediatric primary care offices, where most adolescents receive health care, are a promising venue for early identification of substance use and for brief intervention to prevent associated problems and the development of substance use disorder., Objective: This study tests the effects of a computer-facilitated screening and brief intervention (cSBI) system (the CRAFFT [Car, Relax, Alone, Forget, Family/Friends, Trouble] Interactive System [CRAFFT-IS]) on heavy episodic drinking, riding with a driver who is substance impaired, or driving while substance impaired among adolescents aged 14 to 17 years presenting for a well visit at pediatric primary care practices., Methods: We are conducting a cluster randomized controlled trial of the CRAFFT-IS versus usual care and recruiting up to 40 primary care clinicians at up to 20 pediatric primary care practices within the American Academy of Pediatrics (AAP) Pediatric Research in Office Settings network. Clinicians are randomized 1:1 within each practice to implement the CRAFFT-IS or usual care with a target sample size of 1300 adolescent patients aged 14 to 17 years. At study start, intervention clinicians complete web-based modules, trainer-led live sessions, and mock sessions to establish baseline competency with intervention counseling. Adolescents receive mailed recruitment materials that invite adolescents to complete an eligibility survey. Eligible and interested adolescents provide informed assent (parental permission requirement has been waived). Before their visit, enrolled adolescents seeing intervention clinicians complete a self-administered web-based CRAFFT screening questionnaire and view brief psychoeducational content illustrating substance use-associated health risks. During the visit, intervention clinicians access a computerized summary of the patient's screening results and a tailored counseling script to deliver a motivational interviewing-based brief intervention. All participants complete previsit, postvisit, and 12-month follow-up study assessments. Primary outcomes include past 90-day heavy episodic drinking and riding with a driver who is substance impaired at 3-, 6-, 9-, and 12-month follow-ups. Multiple logistic regression modeling with generalized estimating equations and mixed effects modeling will be used in outcomes analyses. Exploratory aims include examining other substance use outcomes (eg, cannabis and nicotine vaping), potential mediators of intervention effect (eg, self-efficacy not to drink), and effect moderation by baseline risk level and sociodemographic characteristics., Results: The AAP Institutional Review Board approved this study. The first practice and clinicians were enrolled in August 2022; as of July 2023, a total of 6 practices (23 clinicians) had enrolled. Recruitment is expected to continue until late 2024 or early 2025. Data collection will be completed in 2025 or 2026., Conclusions: Findings from this study will inform the promotion of high-quality screening and brief intervention efforts in pediatric primary care with the aim of reducing alcohol-related morbidity and mortality during adolescence and beyond., Trial Registration: ClinicalTrials.gov NCT04450966; https://www.clinicaltrials.gov/study/NCT04450966., International Registered Report Identifier (irrid): DERR1-10.2196/55039., (©Lydia A Shrier, Madison M O'Connell, Alessandra Torres, Laura P Shone, Alexander G Fiks, Julia A Plumb, Jessica L Maturo, Nicholas H McCaskill, Donna Harris, Pamela J Burke, Thatcher Felt, Marie Lynd Murphy, Lon Sherritt, Sion Kim Harris. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.03.2024.)

Purpose: To describe a complex case of ocular tuberculosis reactivation with anterior uveitis, choroiditis and inflammatory choroidal neovascular membrane (CNVM) following immune checkpoint inhibitor (ICPI) treatment of malignant mucosal melanoma., Methods: A retrospective collection of medical history, clinical findings and multimodal imaging with literature review of the topic was conducted., Results: A 52-year-old Romanian female developed reduced vision and photophobia after three cycles of ICPI therapy comprised of ipilimumab and nivolumab. Bilateral anterior uveitis, multiple left eye choroidal lesions and a CNVM were confirmed using slit-lamp examination with ancillary multimodal imaging. Retinal changes in the right eye as well as a history of previously treated posterior uveitis and high-risk ethnicity increased clinical suspicion for ocular tuberculosis (TB) reactivation. The diagnosis was confirmed by TB positivity on polymerase chain reaction (PCR) analysis of lung aspirate followed by significant clinical improvement on systemic anti-tubercular therapy (ATT), systemic steroids and anti-vascular endothelial growth factor (VEGF) therapy., Conclusions: ICPIs can cause a myriad of ocular issues, both by primary immunomodulatory effects as well as secondary reactivation of latent disease., (© 2023. The Author(s).)

Objective: To identify the prevalence of mood disorder diagnoses in patients undergoing cartilage transplantation procedures and determine the relationship between mood disorders, opioid usage, and postoperative health care costs., Design: Patients with current procedural terminology (CPT) codes for osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) were identified in the Truven Health Marketscan database (January 2009-September 2014). Patients were grouped based on having a preoperative mood disorder diagnosis (preMDD). Preoperative opioids, postoperative opioids ≥90 days, and health care costs within the year postoperative were compared for those with and without mood disorders. Costs were analyzed, adjusting for preoperative cost, sex, age, and opioid usage, for those with and without mood disorders., Results: A total of 3,682 patients were analyzed (ACI: 690, OAT: 1,294, OCA: 1,698). A quarter of patients had preMDD (ACI: 25.4%, OAT: 20.6%, OCA: 22.7%). Postoperative opioid use was more prevalent in preMDD patients (OAT: 37.1% vs. 24.1%, P < 0.001; OCA: 30.4% vs. 24.8%, P = 0.032; ACI: 33.7% vs. 26.2%, P = 0.070) (odds ratio [OR] ranged from 1.29 to 1.86). First-year postoperative log-transformed costs were significantly greater for preMDD patients (ACI: $7,733 vs. $5,689*, P = 0.012; OAT: $5,221 vs. $3,823*, P < 0.001; OCA: $6,973 vs. $3,992*, P < 0.001; *medians reported). The estimated adjusted first postoperative year cost increase for preMDD OCA patients was 41.7% ( P < 0.001) and 28.0% for OAT patients ( P = 0.034). There was no statistical difference for ACI patients ( P = 0.654)., Conclusion: Cartilage transplantation patients have a high prevalence of preoperative mood disorders. Opioid use and health care costs were significantly greater for patients with preoperative mood disorder diagnoses., Level of Evidence: Level III, retrospective therapeutic study.

Hypothesis: The purpose of this study was to determine the prevalence and responsiveness of common patient-reported outcome (PRO) tools in patients undergoing primary total shoulder arthroplasty (TSA) for glenohumeral arthritis., Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of anatomic and reverse TSA studies from PubMed, SportDiscus, Cochrane, and CINAHL was performed. Studies on primary TSA for glenohumeral arthritis that reported at least 1 PRO tool were included in the final analysis. A subgroup analysis of studies that reported preoperative and postoperative PRO scores with at least 2-year follow-up data was evaluated to compare the responsiveness between the different PRO instruments., Results: After full-text review of 490 articles, 74 articles met all inclusion criteria and were included in the final analysis. Anatomic TSA was evaluated in 35 studies, reverse TSA in 32 studies, and both anatomic and reverse in 7 studies. There were a total of 7624 patients, and 25 different PRO tools were used. The most commonly reported PRO tools were the American Shoulder and Elbow Surgeons (44 studies), Constant (42 studies), the visual analog scale for pain (23 studies), and the Simple Shoulder Test (17 studies). A median of 3.0 PRO instruments were used in each study. All instruments had large effect sizes. The University of California at Los Angeles (UCLA) score was found to be the most responsive instrument, and the Single Assessment Numeric Evaluation score was least responsive. The American Shoulder and Elbow Surgeons score was the most responsive instrument that required only patient-reported data., Conclusion: Overall, the UCLA score was found to be the most responsive followed by the Adjusted Constant. However, both the UCLA and Adjusted Constant scores require strength and range of motion assessment that may limit their widespread clinical use. The increased responsiveness of these measures, which include objective clinical testing, speaks to the predicted increases in strength and range of motion after shoulder arthroplasty. Of the measures that can be administered without in-person clinical evaluation, the American Shoulder and Elbow Surgeons score and Western Ontario Osteoarthritis of the Shoulder index were the most responsive., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the equipment used for nasal insufflation of oxygen and determine its accuracy., Study Design: Original study., Methods: Oxygen delivery assemblies consisting of a flowmeter, bubble humidifier, oxygen delivery tubing and nasal insufflation catheters were assembled. Single and double catheter assemblies were made for four sizes of nasogastric feeding tubes (3.5 Fr, 5.0 Fr, 8.0 Fr and 10.0 Fr) resulting in 64 individual assemblies. A gas flow analyzer measured oxygen flow at the tip of the nasal catheter assemblies and from the pressure relief valve (PRV) of the bubble humidifiers. Statistical analyses were conducted to assess the functionality of assemblies. For functional assemblies, the accuracy of oxygen flow relative to the prescribed flow settings was determined., Results: Catheter size was significantly associated with the functionality of assemblies. Probability (95% confidence interval) of 3.5 Fr, 5.0 Fr and 8.0 Fr assemblies being functional was estimated at 0.53 (0.14, 0.89), 0.83 (0.36, 0.98) and 0.98 (0.76, 0.99), respectively. All 10.0 Fr assemblies were functional. Functional assemblies, in general, consistently under-delivered the prescribed flow because a large portion of set flow was diverted through the bubble humidifier PRV., Conclusions: Leaks through the PRV cause significant diversion of oxygen prior to it reaching the catheter tips. Smaller patients are particularly susceptible, as small catheters limit oxygen delivery creating proportionally greater leaks through the PRV., Clinical Relevance: It was not possible to accurately deliver oxygen because of leaks through the PRV. Targeting a specific outcome (e.g., oxyhemoglobin saturation > 94%, PaO 2 80-120 mmHg; 11-16 kPa) and avoiding unnecessarily high fractions of inspired oxygen cannot be done if flow delivery cannot be accurately assured. One possible solution would be to use a bubble humidifier with a 6 psi PRV that does not leak prior to reaching the opening pressure., (Published by Elsevier Ltd.)

Introduction: Type 2 diabetes mellitus (T2DM) is a global public health concern. Aerobic physical activity (PA) and resistance training (RT) play significant roles in the prevention and management of T2DM. The aim of this pilot trial is to determine the preliminary efficacy and confirm feasibility of referral to exercise physiologists, psychologists, and provision of a technology-based behavior change support package to promote aerobic PA and RT in school teachers 'at risk' of or diagnosed with T2DM., Research Design and Methods: The SMART (Support, Motivation and Physical Activity Research for Teachers') Health pilot study will be evaluated using a three-arm randomized controlled trial. The intervention will be guided by Social Cognitive Theory, Health Action Process Approach Model and Cognitive Behavioral Therapy strategies. The participants will be randomly allocated to one of three study groups: Group 1: wait-list control group; Group 2: 5 face-to-face visits with a psychologist and exercise specialist over 3 months; and Group 3: same as Group 2 plus technology-based behavior change support package for an additional 6 months. Assessments will be conducted at baseline, 3-, 9- (primary time-point) and 18-months post-baseline. The primary outcome will be PA measured with pedometers., Discussion: SMART Health is an innovative, multi-component intervention, that integrates referral to exercise specialists, psychologists and provision of a technology-based behavior support package to promote PA and RT in adults diagnosed with T2DM or 'at risk' of T2DM. The findings will be used to guide future PA interventions and to develop effective community-based diabetes prevention and treatment programs., Trial Registration: Australian New Zealand Clinical Trials Registry No: ACTRN12616001309471., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

The current health care practice environment has resulted in a crescendo of burnout among physicians, nurses, and advanced practice providers. Burnout among health care professionals is primarily caused by organizational factors rather than problems with personal resilience. Four major drivers motivate health care leaders to build well-being programs: the moral-ethical case (caring for their people), the business case (cost of turnover and lower quality), the tragic case (a physician suicide), and the regulatory case (accreditation requirements). Ultimately, health care provider burnout harms patients. The authors discuss the purpose; scope; structure and resources; metrics of success; and a framework for action for organizational well-being programs. The purpose of such a program is to oversee organizational efforts to reduce the occupational risk for burnout, cultivate professional well-being among health care professionals, and, in turn, optimize the function of health care systems. The program should measure, benchmark, and longitudinally assess these domains. The successful program will develop deep expertise regarding the drivers of professional fulfillment among health care professionals; an approach to evaluate system flaws and relevant dimensions of organizational culture; and knowledge and experience with specific tactics to foster improvement. Different professional disciplines have both shared challenges and unique needs. Effective programs acknowledge and address these differences rather than ignore them. Ultimately, a professional workforce with low burnout and high professional fulfillment is vital to providing the best care to patients. Vanguard institutions have embraced this understanding and are pursuing health care provider well-being as a core organizational strategy.

Background: Awareness of the economic cost of physician attrition due to burnout in academic medical centers may help motivate organizational level efforts to improve physician wellbeing and reduce turnover. Our objectives are: 1) to use a recent longitudinal data as a case example to examine the associations between physician self-reported burnout, intent to leave (ITL) and actual turnover within two years, and 2) to estimate the cost of physician turnover attributable to burnout., Methods: We used de-identified data from 472 physicians who completed a quality improvement survey conducted in 2013 at two Stanford University affiliated hospitals to assess physician wellness. To maintain the confidentially of survey responders, potentially identifiable demographic variables were not used in this analysis. A third party custodian of the data compiled turnover data in 2015 using medical staff roster. We used logistic regression to adjust for potentially confounding factors., Results: At baseline, 26% of physicians reported experiencing burnout and 28% reported ITL within the next 2 years. Two years later, 13% of surveyed physicians had actually left. Those who reported ITL were more than three times as likely to have left. Physicians who reported experiencing burnout were more than twice as likely to have left the institution within the two-year period (Relative Risk (RR) = 2.1; 95% CI = 1.3-3.3). After adjusting for surgical specialty, work hour categories, sleep-related impairment, anxiety, and depression in a logistic regression model, physicians who experienced burnout in 2013 had 168% higher odds (Odds Ratio = 2.68, 95% CI: 1.34-5.38) of leaving Stanford by 2015 compared to those who did not experience burnout. The estimated two-year recruitment cost incurred due to departure attributable to burnout was between $15,544,000 and $55,506,000. Risk of ITL attributable to burnout was 3.7 times risk of actual turnover attributable to burnout., Conclusions: Institutions interested in the economic cost of turnover attributable to burnout can readily calculate this parameter using survey data linked to a subsequent indicator of departure from the institution. ITL data in cross-sectional studies can also be used with an adjustment factor to correct for overestimation of risk of intent to leave attributable to burnout.

Objective: Physician wellness (well-being) is recognized for its intrinsic importance and impact on patient care, but it is a construct that lacks conceptual clarity. The authors conducted a systematic review to characterize the conceptualization of physician wellness in the literature by synthesizing definitions and measures used to operationalize the construct., Methods: A total of 3057 references identified from PubMed, Web of Science, and a manual reference check were reviewed for studies that quantitatively assessed the "wellness" or "well-being" of physicians. Definitions of physician wellness were thematically synthesized. Measures of physician wellness were classified based on their dimensional, contextual, and valence attributes, and changes in the operationalization of physician wellness were assessed over time (1989-2015)., Results: Only 14% of included papers (11/78) explicitly defined physician wellness. At least one measure of mental, social, physical, and integrated well-being was present in 89, 50, 49, and 37% of papers, respectively. The number of papers operationalizing physician wellness using integrated, general-life well-being measures (e.g., meaning in life) increased [X 2  = 5.08, p = 0.02] over time. Changes in measurement across mental, physical, and social domains remained stable over time., Conclusions: Conceptualizations of physician wellness varied widely, with greatest emphasis on negative moods/emotions (e.g., burnout). Clarity and consensus regarding the conceptual definition of physician wellness is needed to advance the development of valid and reliable physician wellness measures, improve the consistency by which the construct is operationalized, and increase comparability of findings across studies. To guide future physician wellness assessments and interventions, the authors propose a holistic definition.

Objective: To determine the accuracy and precision of flowmeters used for oxygen therapy in a veterinary teaching hospital., Study Design: An observational study., Methods: A total of 50 flowmeters used for oxygen therapy were evaluated using Defender 530 gas flow analyzers to measure flow. For each flowmeter, a minimum of seven flow settings were tested in random order and in triplicate. Flow measured at ambient conditions was converted to standardized flow specifications (21.1 °C and 760 mmHg) and analyzed using general linear mixed models. Flowmeters were considered accurate at a given flow setting when the targeted mean flow was within the corresponding 95% confidence interval. Precision of flow was characterized based on the magnitude of variance component estimates., Results: Flowmeters of 1.0, 3.5 and 8.0 L minute -1 were considered accurate across flow settings corresponding to their capacity range. Flowmeters of 7.0 and 15.0 L minute -1 were accurate at flow settings ≤2.0 L minute -1 . For flow settings ≥3.0 L minute -1 , average oxygen flow was consistently below reference values. Precision varied with the capacity of the flowmeter, ranked by decreasing precision as 1.0 > 3.5 > 8.0 > 7.0 > 15.0 L minute -1 ., Conclusions and Clinical Relevance: A flowmeter of the smallest maximum capacity within the desired flow range is more appropriate for smaller patients where accurate, precise flow delivery is needed. Although 15.0 L minute -1 flowmeters were accurate at flow settings ≤2.0 L minute -1 , the graduated increments do not allow exact flow settings <0.5 L minute -1 . Flowmeters of 15 L minute -1 capacity should be useful for high-flow oxygen delivery for which accuracy and precision are not critical., (Published by Elsevier Ltd.)

Recent data have suggested that standard unfractionated heparin (UFH) protocols may over-anticoagulate obese patients. The goal of this retrospective study was to observe differences in anticoagulation parameters and safety outcomes for standardized antifactor Xa UFH protocols in obese and non-obese populations. Obese patients (N = 148) were identified over a 20-month period and matched to 148 non-obese patients based on age, gender, and admission date. Patients were included if they were on one of three approved UFH protocols [high (target antifactor Xa 0.3-0.7 IU/mL), moderate (0.3-0.5 IU/mL), or low (0.1-0.2 IU/mL) dose] for ≥24 consecutive hours and had ≥1 antifactor Xa level drawn during the infusion. Groups were compared for doses at first and second consecutive therapeutic antifactor Xa level, major bleeding, and in-hospital mortality. Obese patients required a significantly lower mean weight-based infusion rate to attain first therapeutic antifactor Xa level compared to non-obese patients in both the high dose (19.45 vs. 15.29 units/kg/h, p < 0.001) and the moderate dose populations (15.0 vs. 12.94 units/kg/h, p = 0.003). Similarly, patients in both the high and moderate dose populations had significant differences in mean infusion rates to attain second consecutive therapeutic antifactor Xa levels. There was no difference between infusion rates for the primary outcomes in the low dose population. There was no difference between groups in major bleeding or mortality outcomes. Similar to data using UFH protocols based on activated partial thromboplastin time, obese patients require lower weight-based UFH doses to attain therapeutic anticoagulation. Institutions using or changing to antifactor Xa based protocols may need to modify protocols for obese patients.

Background: To compare corneal hysteresis (CH) measurements between patients with glaucoma, ocular hypertension (OHT) and glaucoma-like optic discs (GLD)- defined as a cup to disc ratio greater than or equal to 0.6 with normal intraocular pressure (IOP) and visual fields. The secondary aim was to investigate whether corneal resistance factor (CRF) and central corneal thickness (CCT) differ between patient groups., Methods: In this cross sectional study a total of 123 patients (one eye each) were recruited from a glaucoma outpatient department to undergo ocular response analyser (ORA) testing and ultrasound pachymetry as well as clinical examination. A One-way Analysis of Covariance (ANCOVA) was conducted to evaluate the mean difference in CH between the three diagnostic groups (glaucoma, OHT and GLD) correcting for potential confounding factors, IOP and age. Analysis was repeated for CRF and CCT., Results: There was a significant difference in mean CH across the three diagnosis groups; F(2, 115) = 96.95; p < 0.001. Mean CH significantly higher for GLD compared to glaucoma (mean difference 1.83, p < 0.001), and significantly higher for OHT compared to glaucoma (mean difference 2.35, p < 0.001). Mean CH was slightly lower in patients with GLD than those with OHT but this difference was not statistically significant. A similar pattern was seen when the analysis was repeated for CRF and CCT., Conclusions: Higher CH in GLD and OHT compared to glaucoma suggests increased viscoelasticity of ocular tissues may have a protective role against glaucoma.

Background: There are multiple clinical manifestations of hypercalcemia and several causes of hypercalcemia. Hypercalcemia caused by milk-alkali syndrome is increasing in frequency., Case Report: A 26-year-old woman presented after having undergone caesarian section. She complained of severe myalgias, arthralgias, an inability to ambulate, nausea, vomiting, abdominal pain, and marked depression. Each of these symptoms has a broad differential diagnosis, but when considered together the theme "stones, bones, moans, and groans," seen in patients with hypercalcemia, is evident. This patient was found to have hypercalcemia caused by milk-alkali syndrome related to the ingestion of calcium carbonate. Her symptoms and hypercalcemia resolved with treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of the many different symptoms of hypercalcemia. This case emphasizes the need for a careful medication history for any patient presenting with hypercalcemia, including over the counter medications. Physicians should have a high level of suspicion for milk-alkali syndrome in patients with hypercalcemia because milk-alkali syndrome is no longer a rare etiology but rather one of the most common causes of hypercalcemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: General internal medicine (GIM) careers are increasingly viewed as challenging and unsustainable., Objective: We aimed to assess academic GIM worklife and determine remediable predictors of stress and burnout., Design: We conducted an email survey., Participants: Physicians, nurse practitioners, and physician assistants in 15 GIM divisions participated., Main Measures: A ten-item survey queried stress, burnout, and work conditions such as electronic medical record (EMR) challenges. An open-ended question assessed stressors and solutions. Results were categorized into burnout, high stress, high control, chaos, good teamwork, high values alignment, documentation time pressure, and excessive home EMR use. Frequencies were determined for national data, Veterans Affairs (VA) versus civilian populations, and hospitalist versus ambulatory roles. A General Linear Mixed Model (GLMM) evaluated associations with burnout. A formal content analysis was performed for open-ended question responses., Key Results: Of 1235 clinicians sampled, 579 responded (47 %). High stress was present in 67 %, with 38 % burned out (burnout range 10-56 % by division). Half of respondents had low work control, 60 % reported high documentation time pressure, half described too much home EMR time, and most reported very busy or chaotic workplaces. Two-thirds felt aligned with departmental leaders' values, and three-quarters were satisfied with teamwork. Burnout was associated with high stress, low work control, and low values alignment with leaders (all p < 0.001). The 45 VA faculty had less burnout than civilian counterparts (17 % vs. 40 %, p < 0.05). Hospitalists described better teamwork than ambulatory clinicians and fewer hospitalists noted documentation time pressure (both p < 0.001). Key themes from the qualitative analysis were short visits, insufficient support staff, a Relative Value Unit mentality, documentation time pressure, and undervaluing education., Conclusions: While GIM divisions overall demonstrate high stress and burnout, division rates vary widely. Sustainability efforts within GIM could focus on visit length, staff support, schedule control, clinic chaos, and EMR stress.

Although responses to different stressors are sometimes assumed to be similar, recent research has demonstrated that certain types of stress, such as targeted rejection, are particularly potent. To test such associations in a chronic-disease model, we examined how noninterpersonal, interpersonal, and targeted-rejection major life events predicted changes in gene expression and symptom severity in 121 youths with asthma who were assessed every 6 months for 2 years. Youths who had recently experienced targeted rejection had lower messenger RNA expression for signaling molecules that control airway inflammation and obstruction (specifically, the glucocorticoid receptor and β2-adrenergic receptor) than youths who had not experienced targeted rejection. These associations were specific to targeted rejection and stronger for youths higher in subjective social status. Higher-status youths exposed to targeted rejection (but not other types of stress) also reported more asthma symptoms. These data demonstrate stressor-specific associations with molecular-signaling pathways and the severity of asthma, and they suggest that threats to the social self may be particularly deleterious., (© The Author(s) 2015.)

Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers' monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol's anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16- cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers' decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups' monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects' monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Conscientiousness is associated with health, but the mechanisms remain poorly understood. To explore the role that stress might play, this study examined whether conscientiousness was associated with exposure and reactivity to life stress. This study followed 133 adolescent women every 6 months for 2.5 years. Participants completed a baseline measure of conscientiousness, and at each visit underwent a structured interview to catalogue episodic and chronic stress and had blood drawn to assess inflammatory processes. Participants higher in conscientiousness experienced fewer self-dependent episodic stressors and less academic and interpersonal chronic stress throughout the study. However, at times when they experienced higher levels of chronic interpersonal stress, they became more resistant to glucocorticoids. Higher levels of conscientiousness may protect adolescent women from exposure to certain stressors. However, when stress occurs, highly conscientious individuals may become more resistant to glucocorticoids, increasing their risk for processes that influence inflammatory conditions.

Social difficulties during adolescence influence life-span health. To elucidate underlying mechanisms, we examined whether a noxious social event, targeted rejection (TR), influences the signaling pathways that regulate inflammation, which is implicated in a number of health problems. For this study, 147 adolescent women at risk for developing a first episode of major depression were interviewed every 6 months for 2.5 years to assess recent TR exposure, and blood was drawn to quantify leukocyte messenger RNA (mRNA) for nuclear factor-κB (NF-κB) and inhibitor of κB (I-κB) and the inflammatory biomarkers C-reactive protein and interleukin-6. Participants had more NF-κB and I-κB mRNA at visits when TR had occurred. These shifts in inflammatory signaling were most pronounced for adolescents high in perceived social status. These findings demonstrate that social rejection upregulates inflammatory gene expression in youth at risk for depression, particularly for those high in status. If sustained, this heightened inflammatory signaling could have implications for life-span health.

Background: Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and its receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) have been implicated in mood disorders. The aim of this study was to examine whether the NTRK2 and BDNF polymorphisms impact brain white matter connections in major depressive disorder and whether they may also have an interactive effect with environmental stress in the form of early life adversity., Methods: The study group comprised 45 depressed patients and 45 age- and gender-matched control subjects. High angular resolution diffusion images were obtained and analyzed using tract-based spatial statistics. Analysis of a single nucleotide polymorphism in the BDNF (rs6265/Valine66Methionine) and NTRK2 (rs11140714) genes was performed., Results: An interactive effect was found between NTRK2 and depression diagnosis maximally affecting the cingulum. Depressed patients homozygous for the A allele of NTRK2 showed significantly reduced fractional anisotropy compared with depressed patients with at least one copy of the G allele or control subjects with either the A/A or G carrier genotypes in the left and right corona radiata, left uncinate fasciculus, left inferior fronto-occipital fasciculus, left cerebral peduncle, posterior thalamic radiation, and middle cerebral peduncle. Significantly smaller gray matter volume was seen in frontal lobe regions in patients homozygous for the A allele., Conclusions: Polymorphisms in NTRK2 gene increase risk of architectural changes in several brain regions involved in emotional regulation., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The HER3 protein contributes to malignant transformation in breast and other cancer types as a consequence of elevated levels of expression, particularly in the presence of the HER2 protein. We show here that an antibody, called SGP1, to the extracellular domain of the HER3 receptor can inhibit completely Neuregulin stimulated growth of cultured breast cancer cells. Herceptin is a humanised monoclonal antibody to the HER2 protein which has an established role in the treatment of some patients with breast cancer. We demonstrate that Herceptin and SGP1 can bind simultaneously to breast cancer cells expressing both the HER2 and HER3 proteins. In the presence of moderate levels of Herceptin, addition of the SGP1 monoclonal antibody gave a dose-dependent inhibition of the growth of cells expressing both the high levels and moderate levels of HER2. The combination of Herceptin with SGP1 is effective in inhibiting breast cancer cell growth in cases where both HER2 and HER3 are expressed.

Objectives: Identification of the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. To develop D. melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high-throughput toxicity assays and prove that the interindividual variation in toxicity as measured by such assays is highly heritable., Methods: We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose-dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed by a decrease in female fecundity. The chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride., Results: We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose-dependent and a highly heritable manner. The following heritability estimates were found: carboplatin, 0.72; floxuridine, 0.52; gemcitabine hydrochloride, 0.72; methotrexate, 0.99; mitomycin C, 0.64; and topotecan hydrochloride, 0.63., Conclusion: The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component.

Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

Objective: To determine whether group A beta-hemolytic streptococcal infections increase the risk of developing symptoms characteristic of the diagnosis pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)., Design: Prospective cohort study., Methods: Children (N = 814) aged 4 to 11 years seen for sore throat or well-child care in a large pediatric practice in Rochester, NY, were enrolled from October 2001 to June 2002 (group A beta-hemolytic streptococcal [GAS] infected, n = 411; GAS uninfected, n = 403, of whom 207 had a sore throat of presumed viral etiology and 196 were well children). Symptomatic children with GAS infection (n = 399) were treated with antibiotics. At baseline and 2 and 12 weeks following baseline, all parents completed a 20-item questionnaire about the presence/absence of recent PANDAS symptoms in their children, and capable children answered 10 items about worries, obsessions, and compulsions. The relative risk of developing a "mild PANDAS variant" (> or = 2 new PANDAS symptoms) by illness type (GAS positive, presumed viral, or well child) and by parent and child report was determined and adjusted for potential covariates., Results: By parent report, ill children more frequently manifested several PANDAS symptoms at baseline than well children. However, neither new symptoms nor the risk of developing a mild PANDAS variant developed during the subsequent 12 weeks more commonly in children with GAS infection than in those with presumed viral illness or in well children by parent or child report., Conclusions: Ill children with GAS infection, treated for their GAS infection, were not at increased risk for developing PANDAS symptoms or a mild PANDAS variant compared with children with presumed viral illness or well children. The role of antibiotics in the prevention or treatment of PANDAS as well as the investigation of PANDAS in the asymptomatic, infectious host deserves future research.

Rates and extents of ruminal protein degradation for casein, solvent soybean meal (SSBM), expeller soybean meal (ESBM), and alfalfa hay were estimated from net appearance of NH3 and total amino acids in in vitro media containing 1 mM hydrazine and 30 mg/L of chloramphenicol. Protein was added at 0.13 mg of N/mL of medium, and incubations were conducted for 4 to 6 h, usually with hourly sampling. Inocula were obtained from ruminally cannulated donor cows fed diets of grass silage or alfalfa and corn silages plus concentrates. Preincubation or dialysis of inocula was used to suppress background NH3 and total amino acids; however, preincubation yielded more rapid degradation rates for casein and SSBM and was used in subsequent incubations. Preincubation with added vitamins, VFA, hemin, or N did not alter protein degradation. Protein degradation rates estimated for SSBM, ESBM, and alfalfa were not different when computed from total N release or N release in NH3 plus total amino acids, regardless of whether amino acids were quantified using ninhydrin colorimetry or o-phthalaldehyde fluorescence. Accounting for the release of peptide-N also did not affect estimated degradation. However, casein degradation rates were more rapid when using total N release or accounting for peptide-N, indicating significant accumulation of small peptides during its breakdown. Rates also were more rapid with inocula from lactating cows versus nonlactating cows with lower feed intake. Protein degradation rates were different due to time after feeding: casein rate was more rapid, but SSBM and ESBM rates were slower with inocula obtained after feeding. Several characteristics of ruminal inoculum that influenced breakdown of the rapidly degraded protein casein did not appear to have direct effects on degradation of protein in soybean meal.

Effects of varying the concentrations of hydrazine sulfate (HS) and chloramphenicol (CAP), inhibitors of microbial-N uptake and protein synthesis, on rates of protein degradation estimated from net appearance of NH3 and total amino acids (TAA) were studied in a ruminal in vitro fermentation system. Without inhibitors, recoveries of N added as NH3 and TAA were 4 and 6% after 4-h incubations, and apparent degradation rates estimated from release of NH3 and TAA for casein, solvent soybean meal (SSBM), and expeller soybean meal (ESBM) approached 0. Increasing inhibitor concentrations from the standard amounts of 1 mM HS plus 30 mg of CAP/L to 2 mM HS plus 90 mg of CAP/ L gave rise to numerically greater N recoveries and degradation rates, but these differences were not statistically significant. Compared with the standard inhibitor concentrations, use of 2 mM HS, without CAP, yielded similar recoveries and rates, but 30 or 90 mg of CAP/L, without HS, was not satisfactory. Versus that with 1 mM HS plus 30 mg of CAP/L, media containing 2 mM HS plus 90 mg of CAP/L gave increased TAA recoveries and higher rates for casein, but not SSBM, in the presence of added starch. Faster degradation rates were obtained for casein, but slower rates for SSBM and ESBM, in Sweden versus Wisconsin using inocula from cows fed different diets but with similar CP and energy contents. Differences in microbial catabolism of peptides may account for differences in degradation rates observed between Sweden and Wisconsin. Adding NH3 plus free and peptide-bound amino acids to the inoculum reduced apparent degradation rates, possibly via end-product inhibition. Analysis of data from multiple time-point incubations indicated that casein degradation followed simple, first-order kinetics, while a biexponential model fitted degradation patterns for both SSBM and ESBM.

Fifty percent or more of children with upper respiratory infections (URIs) and nonspecific febrile illnesses (e.g., children febrile, anorexic, decreased activity, irritable) receive unnecessary antibiotics from community-based physicians. This study was undertaken to show that white blood cell (WBC) count testing can aid physicians in avoiding antibiotic prescribing when managing children with URIs, and nonspecific febrile illnesses. A prospective, 3-year study was conducted in a community-based pediatric practice. A weekly convenience sample (Tuesdays) of acute URI and febrile patients ages 3 months to 21 years was studied. Data collected on enrollment included: age, gender, duration of illness, recent/current antibiotic use, temperature, symptoms, signs, laboratory testing (WBC count, cultures), diagnosis and treatment. Similar data on any illness visits in the previous 2 weeks and the subsequent 2 weeks after enrollment were collected. Viral culture specimens were obtained on a subset. The use of the WBC count was assessed, including obviating antibiotic prescription, frequency of related follow-up visits, and the occurrence of subsequent bacterial infections. Of 1,956 patients with respiratory or febrile illness enrolled, 1,219 (62%) had a diagnosis established by history and examination (e.g., acute otitis media) and 737 (38%) did not. Of the 737 patients without an established diagnosis, 386 (52%) did not receive an antibiotic because they did not appear particularly ill, their temperature was less than 101 degrees F, and parents were not demanding antibiotics, leaving 351 (48%) patients who appeared ill, had a temperature greater than 101 degrees F, and parents were demanding an antibiotic or physicians were inclined to give an antibiotic. A WBC count was performed on these 351 children; 337 children (96%) had a WBC count less than 15,000/mm3, and 14 (4%) had a WBC 15,000/mm3 or greater. An antibiotic was prescribed for 13 of the 14 children with a WBC count greater than 15,000/mms. With this approach, return office visits in the following 2 weeks were infrequent (13% of 737 patients), and no child had significant bacterial illness that was missed. With selective use of WBC count testing

Background: The current diagnostic criteria for pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) are pediatric onset, neuropsychiatric disorder (obsessive-compulsive disorder [OCD]) and/or tic disorder; abrupt onset and/or episodic course of symptoms; association with group A beta-hemolytic streptococcal (GABHS) infection; and association with neurological abnormalities (motoric hyperactivity or adventitious movements, including choreiform movements or tics)., Objective: To assess new-onset PANDAS cases in relation to acute GABHS tonsillopharyngitis., Design: Prospective PANDAS case identification and follow-up., Results: Over a 3-year period (1998-2000), we identified 12 school-aged children with new-onset PANDAS. Each patient had the abrupt appearance of severe OCD behaviors, accompanied by mild symptoms and signs of acute GABHS tonsillopharyngitis. Throat swabs tested positive for GABHS by rapid antigen detection and/or were culture positive. The GABHS serologic tests, when performed (n = 3), showed very high antideoxyribonuclease antibody titers. Mean age at presentation was 7 years (age range, 5-11 years). In children treated with antibiotics effective in eradicating GABHS infection at the sentinel episode, OCD symptoms promptly disappeared. Follow-up throat cultures negative for GABHS were obtained prospectively after the first PANDAS episode. Recurrence of OCD symptoms was seen in 6 patients; each recurrence was associated with evidence of acute GABHS infection and responded to antibiotic therapy, supporting the premise that these patients were not GABHS carriers. The OCD behaviors exhibited included hand washing and preoccupation with germs, but daytime urinary urgency and frequency without dysuria, fever, or incontinence were the most notable symptoms in our series (58% of patients). Symptoms disappeared at night, and urinalysis and urine cultures were negative., Conclusion: To our knowledge, this is the first prospective study to confirm that PANDAS is associated with acute GABHS tonsillopharyngitis and responds to appropriate antibiotic therapy at the sentinel episode.

Human visceral leishmaniasis (VL) results in a severe and potentially fatal systemic disease, accompanied by cellular immune depression. The production of IL-10 correlates with ongoing disease and it has been suggested that the cellular immune depression that accompanies active disease may be due to a predominance of IL-10 production rather than a lack of IFN-gamma production, which is essential for optimal macrophage activation and parasite elimination. To examine the role of IL-10 in resistance during L. donovani infection (a causative agent of VL), the course of infection was examined in mice lacking the gene for IL-10. BALB/c IL-10-/-, as well as C57BL/6 IL-10-/- mice, were highly resistant to L. donovani infection, as evidenced by liver parasite burdens which were tenfold lower than those in control mice after 14 days of infection. Enhanced resistance was accompanied by increased production of IFN-gamma and nitric oxide in BALB/c IL-10-/- mice. Susceptibility to infection in BALB/c IL-10-/- mice was enhanced following in vivo treatment with a neutralizing antibody to IFN-gamma or IL-12. Together these studies demonstrate for the first time that IL-10 is a critical component of the immune response that inhibits resistance to L. donovani.

Objective: To compare 5-, 7- and 10-day duration of antibiotic therapy for acute otitis media (AOM) in children., Study Design and Setting: Prospective nonrandomized 1-year evaluation of 3 treatment durations for AOM in a private pediatric setting. Outcomes assessed at 14 +/- 4 days after start of therapy with clinical response categorized as cure, improvement, or failure., Results: A total of 2172 children were studied; 46.4% were < or =2-years-old. Antibiotics used were amoxicillin (61.9% of patients), trimethoprim/sulfamethoxazole (11.7%), cephalosporins (14.2%), amoxicillin/clavulanate (5.2%), and macrolides/azalides (4.8%). No overall difference in outcome was observed comparing the 5-day (n = 707), 7-day (n = 423), or 10-day (n = 1042) treatments, including children < or =2-years-old. However, in the subset who had an episode of AOM in the preceding month, outcome differed; 5-day treatment was followed by more frequent failure than 10-day treatment (P < 0.001). In logistic regression analysis, variables identified as contributing to a cure were: >2-years-old (P < 0.0001), no AOM in the preceding month (P = 0.07), or preceding 12 months (P = 0.03)., Conclusions: Our study supports the transition from 10 to 5 days for standard AOM antibiotic treatment duration in most patients. A 10-day regimen may be superior in children who have experienced an episode of AOM within the preceding month, a known risk factor for resistant bacterial infection in the otitis-prone patient.

Purpose: To determine a relationship between preoperative soft tissue disruption and postoperative ocular motility in orbital blowout fractures., Methods: This retrospective cohort study reviewed 30 patients who met all criteria: retrievable coronal computed tomography (CT) scans; internal fractures of the orbital floor, with or without medial wall extension; preoperative diplopia; repair by a single surgeon; complete release of entrapped tissues; and postoperative binocular visual fields (BVFs). Motility outcomes were quantified by one group of the authors, who measured the vertical fusion within BVFs. Other authors analyzed CT scans, designating each fracture as either A or B, based on lesser or greater soft tissue distortion relative to the configuration of bone fragments. The interval between trauma and surgery was also determined., Results: Among the 15 patients with a postoperative motility outcome poorer than the median (86 degrees or less), four (27%) had A fractures; 11 (73%) had B fractures. Among the 15 patients with an outcome better than the median (88 degrees or more), 10 (67%) had A fractures; five (33%) had B fractures. Differences were more defined away from the median. Among five patients with B fractures and better than the median result, three (60%) had surgical repair during the first week after injury. Among the 11 patients with B fractures and less than the median result, one (9%) had repair during the first week., Conclusions: Postoperative motility is influenced by soft tissue-bone fragment relationships. Whether the outcome can be altered by earlier surgery in selected cases will be determined by prospective studies.