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The incidence of periprosthetic proximal femoral fractures is increasing with the increase in arthroplasty being performed as well as aging populations. We describe an open reduction and internal fixation and cement-in-cement technique utilizing a well-fixed cement mantle. The advantages of this allow for a shorter operative time, reduction in risk of iatrogenic femoral fractures, and reduction in blood loss. This was a retrospective study reviewing 20 patients that underwent this technique for periprosthetic fractures. Thirty percent (n = 6) of patients underwent subsequent surgery. We had a 95% (n = 19) union rate with 1 case refracturing through the old fracture. This technique can allow for shorter operative times and a lower physiological insult in reducible periprosthetic proximal femur fractures with a stable cement mantle.

The move by businesses to cut health-care costs has both increased out-of-pocket costs for insured employees and increased the use of part-time workers who are less likely to be covered by employer health insurance. What are the trends in inadequate or nonexistent hospitalization insurance? What are the economic effects of medical indigence? [ABSTRACT FROM AUTHOR]

With mental health needs consistently increasing in our communities and medical centers, we want to ensure that institutions are aware of the benefit and value that psychologists bring to their system and provide several pathways for consideration and structure to understand how to support the salaries and careers of psychologists working within AHCs. Leadership and administration within Academic Health Centers (AHC) often do not understand the value and measurement of productivity for psychologists being added to the medical teams. The current article aims to present varied structural models and demonstrate how productivity is reviewed for psychologists across different institutions and departments. The authors will outline the many roles that psychologists serve within academic health centers as well as the value those roles bring to the system. The overarching goal is to provide an educational article that serves as a tool for recruitment of psychologists that leaders and faculty can refer to when approaching administration in AHCs to understand the systems and roles of psychologists within medical settings. This information can be utilized to help create new positions for psychologists, aid in recruitment efforts and provide transparency for faculty currently working within AHCs who may not be aware of the varied opportunities., (© 2024. The Author(s).)

Background: Reports of technical success, adverse events, and long-term outcome of percutaneous cecostomy in children are limited., Objective: To characterize technical success, 30-day severe adverse events, and long-term outcome of percutaneous cecostomy at two centers., Materials and Methods: A retrospective review of hospital course and long-term follow-up (through May 2022) of percutaneous cecostomy tubes placed May 1997 to August 2011 at two children's hospitals was used. Outcomes assessed included technical success (defined as successful tube placement into the colon allowing antegrade colonic enemas), length of stay, 30-day severe adverse events, surgery consults, surgical repair, VP shunt infection, ongoing flushes, tube removal, duration between maintenance tube exchanges, and deaths., Results: A total of 215 procedures were performed in 208 patients (90 institution A, 125 institution B). Tubes were placed for neurogenic bowel (72.1%, n = 155) and functional constipation (27.9%, n = 60). Technical success was 98.1% (211/215) and did not differ between centers (p = 0.74). Surgical repair was required for bowel leakage in 5.1% (11/215) and VP shunt infection was managed in 2.1% (2/95). Compared to functional constipation, patients with neurogenic bowel had higher % tube remaining (65.3% [96/147] versus 25.9% [15/58], p < 0.001) and higher ongoing flushes at follow-up (42.2% [62/147] versus 12.1% [7/58], p < 0.001). Tube removal for dissatisfaction occurred in 15.6% [32/205] and did not differ between groups (p = 0.98). Eight deaths due to co-morbidity occurred after a median of 7.4 years (IQR 9.3) of tube access., Conclusion: Percutaneous cecostomy is technically successful in the vast majority of patients and provided durable access in most. Bowel leakage and VP shunt infection are uncommon, severe adverse events., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Female sexual dysfunction (FSD) affects an estimated 40% of women. Unfortunately, FSD is understudied, leading to limited treatment options for FSD. Neuromodulation has shown some success in alleviating FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD., Materials and Methods: This study comprises a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations., Results: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations., Conclusions: To our knowledge, this is the first study to measure sexual arousal in response to short-term neuromodulation in women. This study indicates that short-term DGNS but not TNS can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for FSD., Competing Interests: Conflict of Interest Tim M. Bruns reports serving on the Scientific Advisory Board and received stock options for Stimulai Therapeutics. Priyanka Gupta reports serving on the Medical Advisory Board and received stock options for Stimulai Therapeutics. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Chronic wasting disease (CWD) is a highly infectious, fatal prion disease that affects cervid species. One promising method for CWD surveillance is the use of detection dog-handler teams wherein dogs are trained on the volatile organic compound signature of CWD fecal matter. However, using fecal matter from CWD-positive deer poses a biohazard risk; CWD prions can bind to soil particles and remain infectious in contaminated areas for extended periods of time, and it is very difficult to decontaminate the affected areas. One solution is to use noninfectious training aids that can replicate the odor of fecal matter from CWD-positive and CWD-negative deer and are safe to use in the environment. Trained CWD detection dogs' sensitivity and specificity for different training aid materials (cotton, GetXent tubes, and polydimethylsiloxane, or PDMS) incubated with fecal matter from CWD-positive and CWD-negative deer at two different temperatures (21 °C and 37 °C) for three different lengths of time (6 h, 24 h, and 48 h) were evaluated. Cotton incubated at 21 °C for 24 h was identified as the best aid for CWD based on the dogs' performance and practical needs for training aid creation. Implications for CWD detection training and for training aid selection in general are discussed.

Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy that affects both free-ranging and farmed cervid species, including mule deer, white-tailed deer, and elk ( Odocoileus hemionus, Odocoileus virginianus , and Cervus canadensis ). Due to the long incubation period and variability of clinical signs, CWD can expand and spread to new areas before they reach diagnostically detectable levels. Antemortem testing methods currently available can be difficult to obtain and to be applied to the large numbers required for adequate surveillance. However, key volatile biomarkers could be harnessed for non-invasive antemortem surveillance. Detection dogs are the most effective tool currently available for volatile detection; dogs can effectively complete wildlife surveys at rates surpassing that of humans. This study is the first to demonstrate that trained detection dogs can be used as an antemortem test for CWD. First, we trained three dogs to differentiate between CWD-positive and CWD-negative white-tailed deer faeces in a laboratory setting. Dogs spent significantly more time at the positive sample than the negative samples, suggesting that they differentiated between the positive and negative volatile signatures. We then trained the same dogs to search for CWD-positive faecal samples in a more naturalistic field setting. In the field, dogs found 8/11 CWD-positive samples and had an average false detection rate of 13%. These results suggest that dogs can be trained to differentiate CWD-positive faeces from CWD-negative faeces in both laboratory and field settings. Future studies will compare canine accuracy to other antemortem methods, as well as improved canine training methods.

Background: While chest tube placement with pleural fibrinolytic medication is the established treatment of pediatric empyema, treatment failure is reported in up to 20% of these children., Objective: Standardizing fibrinolytic administration among interventional radiology (IR) physicians to improve patient outcomes in pediatric parapneumonic effusion., Materials and Methods: We introduced a hospital-wide clinical pathway for parapneumonic effusion (1-2 mg tissue plasminogen activator [tPA] twice daily based on pleural US grade); we then collected prospective data for IR treatment May 2017 through February 2020. These data included demographics, co-morbidities, pediatric intensive care unit (PICU) admission, pleural US grade, culture results, daily tPA dose average, twice-daily dose days, skipped dose days, pleural therapy days, need for chest CT/a second IR procedure/surgical drainage, and length of stay. We compared the prospective data to historical controls with IR treatment from January 2013 to April 2017., Results: Sixty-three children and young adults were treated after clinical pathway implementation. IR referrals increased (P = 0.02) and included higher co-morbidities (P = 0.005) and more PICU patients (P = 0.05). Mean doses per day increased from 1.5 to 1.9 (P &lt; 0.001), twice-daily dose days increased from 38% to 79% (P &lt; 0.001) and median pleural therapy days decreased from 3.5 days to 2.5 days (P = 0.001). No IR patients needed surgical intervention. No statistical differences were observed for gender/age/weight, US grade, need for a second IR procedure or length of stay. US grade correlated with greater positive cultures, need for chest CT/second IR procedure, and pleural therapy days., Conclusion: Interventional radiology physician standardization improved on a clinical pathway for fibrinolysis of parapneumonic effusion. Despite higher patient complexity, pleural therapy duration decreased. There were no chest tube failures needing surgical drainage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Asian Americans comprise 21% of matriculating medical students in the United States but little is known about their mental health. With the growing focus on addressing the mental health of medical students, this systematic, nationwide survey assesses the relationship between anxiety and depression symptoms and coping skills among Asian American medical students., Materials and Methods: A survey tool comprised of Patient Health Questionnaire-9, General Anxiety Disorder-7, and questions related to coping were emailed to members of the Asian Pacific American Medical Students Association enrolled in a United States medical school during the 2016-2017 academic year. We evaluated associations between anxiety and coping as well as depression and coping., Results: A total of 511 Asian American medical students completed the survey. Anxiety symptoms were positively correlated with an increase in negative coping skills. Depressive symptoms were not correlated with an increase in negative coping skills., Conclusion: Professionals and medical schools that aim to improve the mental health of medical students should be aware of the needs of specific populations. Asian American students who experience anxiety were more likely to utilize avoidant or negative coping strategies. In addition, Asian American students who experience depressive symptoms were not more likely to utilize these negative coping strategies. Further research must be done to evaluate the factors that influence the use of negative coping strategies to better address anxiety within the Asian American medical student population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moore, Yang, Raines, Bailey and Beg.)

Venous thromboembolism (VTE) is associated with potentially preventable in-hospital morbidity and mortality. Although evidence-based guidelines are widely available, their application in clinical practice varies markedly. VTE prophylaxis involves a multistep dynamic process that can fail at various points during hospital stay. Our aim was to identify defects in VTE prophylaxis. Upon admission, our patients undergo VTE risk stratification and orders for prophylaxis are entered. All patients that fulfill the criteria for the Patient Safety Indicator (PSI)-12, as defined by the Agency for Healthcare Research and Quality, are prospectively entered in a database. From a review of 138 PSI-12 patients, only 21 had correct risk stratification and appropriate chemoprophylaxis during their hospital stay; 70 had been incorrectly stratified, with 28 of these patients receiving incorrect prophylaxis due to incorrect stratification, thus delaying the correct administration of chemoprophylaxis for >24 h. Inadequate application of mechanical prophylaxis was noted in 114 patients. VTE prophylaxis relies on correct risk stratification, ordering appropriate pharmacomechanical measures and, finally, the delivery of this treatment throughout the hospital stay. A large percentage of patients who had a thromboembolic complication received inadequate prophylaxis. This study identifies potential areas for intervention to improve VTE prophylaxis.

Purpose: Recent data reported that 21.5% of medical students in the United States of America (USA) are Asian American (AA). With the growing focus on developing medical school wellness programs, authors conducted a systematic, nationwide survey to assess prevalence of depression among AA medical students with a focus on disaggregating the AA population., Methods: A survey tool comprised of PHQ-9 and depression history, and questions on social support were emailed to members of the Asian Pacific American Medical Students Association enrolled in a USA medical school during the 2016-2017 academic year. Participants were grouped as East Asian American (EAA), Southeast Asian American (SEAA), and South Asian American (SAA). We evaluated associations between depression and regional ethnicity, depression history, and perceived support., Results: A total of 457 AA medical students were surveyed. SAA medical students were more likely to endorse symptoms of depression than EAA students. Students who identified as female were more likely to endorse symptoms of depression than their male-identifying counterparts. There was no significant relationship between students' perception of the support they received and their depressive symptoms., Conclusion: Medical school administration should be aware of the unique needs of the heterogeneous population that comprises AA medical students. SAA students and those who identify as female are more likely to endorse symptoms of depression than their AA counterparts. Further research must be done to evaluate the factors that influence the mental health needs of AA medical students., (© 2021. W. Montague Cobb-NMA Health Institute.)

Objective: To assess the impact of the temporary cessation of orthodontic services on patients undergoing treatment during the COVID-19 pandemic., Design: Two-phase multicentre service evaluation., Setting: Secondary care orthodontic departments in the South West of England., Materials and Methods: Phase 1 - Patient-Reported Experience Measure questionnaire (PREM). The questionnaire was distributed to patients who had undergone orthodontic treatment during the COVID-19 pandemic once services had resumed. Phase 2 - assessment of treatment outcomes, specifically with the Peer Assessment Rating (PAR) Index. A total of 280 PAR scores were obtained from a cohort of patients treated before and during the pandemic., Results: A total of 711 PREM questionnaires were completed. Participants generally felt relaxed when visiting secondary care settings, orthodontic departments and whilst wearing orthodontic appliances during the pandemic. Nearly 40% of participants were concerned that the pandemic would impact on their treatment, particularly treatment length. Treatment outcomes revealed that patients treated before and during the pandemic experienced percentage PAR score reductions of 83.9% and 80.6%, respectively. Patients receiving treatment during the pandemic experienced longer treatment durations of 126 days., Conclusion: During the pandemic, low levels of anxiety were reported with respect to receiving orthodontic treatment in secondary care settings. Irrespective of the pandemic, a high standard of orthodontic treatment was provided. However, patient concerns regarding treatment length were justified.

Context: A genetic etiology likely accounts for the majority of unexplained primary ovarian insufficiency (POI)., Objective: We hypothesized that heterozygous rare variants and variants in enhanced categories are associated with POI., Design: The study was an observational study., Setting: Subjects were recruited at academic institutions., Patients: Subjects from Boston (n = 98), the National Institutes of Health and Washington University (n = 98), Pittsburgh (n = 20), Italy (n = 43), and France (n = 32) were diagnosed with POI (amenorrhea with an elevated follicle-stimulating hormone level). Controls were recruited for health in old age or were from the 1000 Genomes Project (total n = 233)., Intervention: We performed whole exome sequencing (WES), and data were analyzed using a rare variant scoring method and a Bayes factor-based framework for identifying genes harboring pathogenic variants. We performed functional studies on identified genes that were not previously implicated in POI in a D. melanogaster model., Main Outcome: Genes with rare pathogenic variants and gene sets with increased burden of deleterious variants were identified., Results: Candidate heterozygous variants were identified in known genes and genes with functional evidence. Gene sets with increased burden of deleterious alleles included the categories transcription and translation, DNA damage and repair, meiosis and cell division. Variants were found in novel genes from the enhanced categories. Functional evidence supported 7 new risk genes for POI (USP36, VCP, WDR33, PIWIL3, NPM2, LLGL1, and BOD1L1)., Conclusions: Candidate causative variants were identified through WES in women with POI. Aggregating clinical data and genetic risk with a categorical approach may expand the genetic architecture of heterozygous rare gene variants causing risk for POI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

N-acetylglutamate synthase deficiency is an autosomal recessive urea cycle disorder caused either by decreased expression of the NAGS gene or defective NAGS enzyme resulting in decreased production of N-acetylglutamate (NAG), an allosteric activator of carbamylphosphate synthetase 1 (CPS1). NAGSD is the only urea cycle disorder that can be effectively treated with a single drug, N-carbamylglutamate (NCG), a stable NAG analog, which activates CPS1 to restore ureagenesis. We describe three patients with NAGSD due to four novel noncoding sequence variants in the NAGS regulatory regions. All three patients had hyperammonemia that resolved upon treatment with NCG. Sequence variants NM&#95;153006.2:c.427-222G>A and NM&#95;153006.2:c.427-218A>C reside in the 547 bp-long first intron of NAGS and define a novel NAGS regulatory element that binds retinoic X receptor α. Sequence variants NC&#95;000017.10:g.42078967A>T (NM&#95;153006.2:c.-3065A>T) and NC&#95;000017.10:g.42078934C>T (NM&#95;153006.2:c.-3098C>T) reside in the NAGS enhancer, within known HNF1 and predicted glucocorticoid receptor binding sites, respectively. Reporter gene assays in HepG2 and HuH-7 cells demonstrated that all four substitutions could result in reduced expression of NAGS. These findings show that analyzing noncoding regions of NAGS and other urea cycle genes can reveal molecular causes of disease and identify novel regulators of ureagenesis., (© 2021 Wiley Periodicals LLC.)

Background and Aims: Percutaneous gastrostomy (PEG) is a common inpatient procedure. Prior data from National Inpatient Sample (NIS) in 2006 reported a mortality rate of 10.8% and recommended more careful selection of PEG candidates. This study assessed for improvement in the last 10 years in mortality rate and complications for hospitalized patients., Methods: A retrospective cohort analysis of all adult inpatients in the NIS from 2006 to 2016 undergoing PEG placement compared demographics and indication for PEG placement per ICD coding. Survey-based means and proportions were compared to 2006, and rates of change in mortality and complication rates were trended from 2006 through 2016 and compared with linear regression. Multivariable survey-adjusted logistic regression was used to determine predictors of mortality and complications in the 2016 sample., Results: A total of 155,550 patients underwent PEG placement in 2016, compared with 174,228 in 2006. Mortality decreased from 10.8 to 6.6% without decreased comorbidities (p < 0.001). This trend was gradual and persistent over 10 years in contrast to a stable overall inpatient mortality rate (p = 0.113). Stroke remained the most common indication (29.7%). The majority of patients (64.6%) had Medicare. Indications for placement were stable. Complication rates were stable from 2006 (4.4%) to 2016 (5.1%) (p = 0.201)., Conclusions: Inpatient PEG placement remains common. Despite similar patient characteristics, mortality has decreased by approximately 40% over the last 10 years without a decrease in complications likely reflecting improved patient selection.

Introduction: Patients hospitalized with myocardial infarction (MI) are at risk of gastrointestinal bleeding because of the need for antiplatelet agents and/or anticoagulation. The data regarding the safety of endoscopy after MI are limited. This study sought to assess mortality rates of patients hospitalized with acute MI who require esophagogastroduodenoscopy or colonoscopy using the National Inpatient Sample (NIS) database., Methods: A retrospective cohort analysis of all adult inpatients in the NIS from 2016 admitted for ST-elevation infarction myocardial infarction (STEMI), non-STEMI, or type II non-STEMI was conducted. Data were collected including patient demographics and indication for endoscopy per ICD-10 coding. HCUPnet was used to query NIS to obtain all inpatient mortality. The primary methods included adjusted χ for categorical outcomes, adjusted linear regression for continuous outcomes, and adjusted logistic regression for multivariable analysis., Results: A total of 1,281,749 patients were admitted for acute coronary syndrome in 2016, and 55,035 of these patients underwent endoscopy In the multivariable regression analysis, those who underwent a GI procedure (odds ratio [OR] 0.80, P value < 0.002) and angiogram (OR 0.48, P value < 0.001) had lower in-hospital mortality, after adjusting for age, Elixhauser index, need for angiogram, sex, race, and hospital type. Endoscopy postcatheterization was not associated with a difference in mortality compared with preangiogram (OR = 0.84, 95% confidence interval 0.60-1.19)., Discussion: Patients who underwent endoscopy are sicker and have higher mortality rates than those who do not undergo endoscopy, but after adjusting for comorbidities, mortality is actually lower. This suggests that endoscopy is safe and should be performed when clinically indicated despite recent cardiac ischemia.

Introduction: The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment., Methods: This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year., Results: Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ 2 (1, N = 56) = 19.2, p < 0.0001)., Conclusions: There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to identify optimal duration of TMZ therapy.

Posttraumatic stress disorder (PTSD) is a chronic and debilitating condition for which clinicians sometimes turn to anticonvulsants as a treatment for symptoms. This study was a systematic review and meta-analysis of randomized controlled trials (RCT) that have assessed the efficacy of topiramate as monotherapy or adjunctive therapy, compared to placebo, for the treatment of PTSD in adults. Prescribers may be reluctant to turn to topiramate, given the commonly reported side effects of impaired cognition, sedation, fatigue, and headache. We searched PubMed, PsycInfo, and Cochrane Central databases for relevant trials. Five studies were identified as RCTs and thus met inclusion criteria; one additional nonpublished study was identified via phone contact with its authors. Of these six studies, one was excluded from the statistical meta-analysis due to its high dropout rate (16 of 40 participants). One of these studies was excluded from a stratified analysis of symptom types because this subscale data were unavailable.  For overall symptomatology, topiramate showed a medium, but not significant effect, standardized mean difference (SMD) = 0.55, p = .082. Topiramate showed a small and significant reduction of hyperarousal symptoms, SMD = 0.35, 95% CI [0.029, 0.689], p = .033. Topiramate did not significantly reduce reexperiencing symptoms, SMD = 0.29, 95% CI [-0.019, 0.597], p = .067, or avoidance symptoms, SMD = 0.20, 95% CI [-0.105, 0.509], p = .198. Results did not differ significantly between veteran and nonveteran subjects, or between topiramate as monotherapy and adjunctive therapy. Further studies on topiramate will clarify its role in PTSD treatment., (Copyright © 2018 International Society for Traumatic Stress Studies.)

Objectives: Pain is a common side effect of orthodontic treatment. An objective of this study, part of a large previously reported RCT on pain and analgesic use, was to determine the effect of anxiety on perceived pain and use of analgesia., Methods: 1000 patients aged 11-17 years, undergoing upper and lower fixed appliance treatment in nine hospital departments were recruited into this two-arm parallel design randomised controlled trial. One arm was given sugar-free chewing gum and the other arm ibuprofen for pain relief. Neither the clinicians nor patients were blinded to assignment. In addition to recording pain experience and analgesic use for 3 days following appliance placement and first archwire change, each patient recorded their level of anxiety immediately following the fitting of the appliance and the first archwire change., Results: 419 chewing gum group (84%) and 407 ibuprofen group (83%) questionnaires were returned following appliance placement, and 343 chewing gum group (70%) and 341 ibuprofen group (71%) questionnaires were returned following the first archwire change. The mean anxiety scores following fitting of the appliance and first archwire change were 2.7 (SD 2.1) and 1.6 (SD 1.8), respectively. There were weak but significant positive associations between anxiety scores and pain scores. Multi-level modelling produced a coefficient for anxiety of 0.23 (95% CI 0.17-0.28) for appliance placement, suggesting a small rise (0.23) on the 11-point pain scale for a one-point increase on the corresponding anxiety scale. Following archwire change, the corresponding coefficient was 0.32 (0.24-0.39). For ibuprofen use, again simple analyses suggested a relationship with anxiety. Multi-level logistic modelling produced an odds ratio for ibuprofen use of 1.11 (95% CI 1.07-1.15) at appliance placement and 1.21 (1.10-1.33) at the first archwire change. There was a 10-20% increase in the odds of using ibuprofen for each one-point increase on the anxiety scale. No such relationship was found between anxiety and chewing gum use. There were no adverse effects or harms reported during the trial. Approvals were granted by the Research Ethics Committee (08/H0106/139), R&D and MHRA (Eudract 2008-005522-36) and the trial was registered on the ISRCTN (79884739) and NIHR (6631) portfolios. Support was provided by the British Orthodontic Society Foundation., Conclusions: There was a weak positive correlation between anxiety reported and pain experienced following both the initial fitting of the fixed appliances and at the subsequent archwire change. Patients that were more anxious tended to take more ibuprofen for their pain relief.

Background: Complicated pleural effusion prolongs the hospital course of pneumonia. Chest tube placement with instillation of fibrinolytic medication allows efficient drain output and decreases hospital stay., Objective: To evaluate experience with lower fibrinolytic dose for parapneumonic effusions and to assess potential dose stratification based on a simple ultrasound grading system., Materials and Methods: We retrospectively reviewed the medical record to identify children and young adults who received fibrinolytic therapy for parapneumonic effusion and had chest tube placement by an interventional radiology service at a single children's hospital. We assessed tissue plasminogen activator (tPA) dosing and treatment duration, as well as the need for a second pleural procedure or surgical drainage. Diagnostic US images were classified as showing less than 50% pleural echogenicity (grade 1) or greater than 50% pleural echogenicity (grade 2) and were correlated with clinical parameters., Results: Of 32 patients with parapneumonic effusion, all except one received at least some 1-mg tPA doses. Dosing was solely 1-mg tPA in 81% of subjects; 19% of subjects also received 2-mg tPA doses. Mean fibrinolytic duration was 3.1 days for grade 1 effusions compared to 5.4 days for grade 2 effusions. A second pleural procedure was required in 15.6% of children. Pleural drainage with fibrinolytic therapy was successful in 97%; only one child required surgical drainage. Grade 2 US differed significantly from grade 1 US, with grade 2 occurring in younger patients (P < 0.0001), smaller patients (P < 0.0001), those needing a second procedure (P = 0.001), those with positive pleural culture or polymerase chain reaction test (P = 0.006), and those with longer treatment duration (P = 0.03)., Conclusion: A lower 1-mg dosing regimen of tissue plasminogen activator was effective in all children with less complex (grade 1 US imaging) parapneumonic effusions. Grade 2 US images correlated with younger and smaller children, presence of a pleural organism, and longer or more complicated chest tube duration.

Background: Literature reports suggest that phytochemicals, such as isoflavones found in soybeans, impair reproductive function in animals and raise the possibility that consuming soy infant formula could alter hormonally sensitive organ development in children., Objective: This study compared reproductive organs volumes and structural characteristics in children at age 5 y who were enrolled in the Beginnings study long-term cohort., Methods: Breast bud, uterus, ovaries, prostate, and testes volumes and characteristics were assessed by ultrasonography in 101 children (50 boys and 51 girls) aged 5 y who were breastfed (n = 35) or fed cow-milk formula (n = 32) or soy formula (n = 34) as infants. Analyses were adjusted for race, gestational age, and birth weight., Results: Among girls, no significant differences were found in breast bud, ovarian, or uterine volumes; counts of ovaries with cysts; ovarian cysts numbers; ovarian cyst size; and uterine shape between the diet groups. Among boys, no significant differences were found in breast bud, testes, or prostate volumes or structural characteristics between the diet groups., Conclusions: In this cohort, no early infant feeding effects were found on reproductive organs volumes and structural characteristics in children age 5 y. The follow-up of these children through puberty is planned and should help delineate potential early infant feeding effect on reproductive function later in life., (© 2015 American Society for Nutrition.)

Introduction: This paper explores the impact of recruiting patients to a randomised controlled trial (RCT) at recruiting centres. This large multicentre RCT examining the efficacy of chewing gum compared to ibuprofen in the relief of orthodontic pain was carried out across nine recruiting centres., Method: The work diaries of clinicians and supporting staff at recruiting centres were analysed over a four-month period from September to December 2011. This quantified the amount of clinical and non-clinical time spent on research duties., Results: Over this time period 98 patients were recruited across seven trial sites. On average, patient recruitment had a direct clinical impact of 19 minutes per patient recruited. The time commitment on trial administration outside the clinical sessions was much higher, averaging at 110 minutes per patient recruited, giving the overall time spent on the trial 129 minutes per patient., Conclusions: This information will be valuable to lead researchers when calculating the full economic cost of a proposed clinical trial and therefore when applying for grant funding. It may also be valuable to clinicians and their managers when considering becoming a principle investigator (PI) in a RCT. Although the impact on clinical time was 19 minutes per patient recruited, there is a considerably higher (almost six times greater) time commitment in administration around the recruitment of patients.

Purpose: To analyze the operative benefit of preoperative sclerotherapy of facial venous malformations and assess long-term patient outcome., Materials and Methods: Preoperative sclerotherapy was performed in 24 consecutive patients referred before resection of facial venous malformation. Pretreatment imaging was reviewed for malformation dimensions (length, width, and height), and volumes were estimated. Sclerotherapy was performed with 3% sodium tetradecyl in the first 15 patients and 98% dehydrated alcohol in the remaining 9 patients. Operative blood loss, operative time, transfusion requirement, and hospital stay were recorded. Operative time per lesion volume and operative blood loss per lesion volume were calculated. Results were compared with 15 historical control patients who underwent resection of facial venous malformations without preoperative sclerotherapy. Long-term follow-up of study and control patients was performed., Results: Compared with controls, patients undergoing preoperative venous sclerotherapy were significantly older (P = .0206) and had larger lesions in all three dimensions (height, P = .0002; length, P = .0010; width, P = .0004). Patients receiving sclerotherapy had shorter operative time per lesion volume (P < .0001) and reduced blood loss per lesion volume (P < .0001). Neither hospital stay nor the need for blood transfusion differed from the control patients (P = .2449 and P = .6857). Mild periprocedural complications were encountered in 12.5% of cases, and nerve paresis occurred in 8.3% of cases. Long-term follow-up revealed retreatment was required in 2 of 24 patients (8.3%)., Conclusions: Preoperative sclerotherapy of venous malformations was associated with less operative time per lesion volume and less operative blood loss per lesion volume. Long-term follow-up revealed a low need for retreatment., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if differences exist in hormone-sensitive organ size between infants who were fed soy formula (SF), milk formula (MF), or breast milk (BF)., Study Design: Breast buds, uterus, ovaries, prostate, and testicular volumes were assessed by ultrasonography in 40 BF, 41 MF, and 39 SF infants at age 4 months., Results: There were no significant feeding group effects in anthropometric or body composition. Among girls, there were no feeding group differences in breast bud or uterine volume. MF infants had greater (P < .05) mean ovarian volume and greater (P < .01) numbers of ovarian cysts per ovary than did BF infants. Among boys, there were no feeding group differences in prostate or breast bud volumes. Mean testicular volume did not differ between SF and MF boys, but both formula-fed groups had lower volumes than BF infants., Conclusions: Our data do not support major diet-related differences in reproductive organ size as measured by ultrasound in infants at age 4 months, although there is some evidence that ovarian development may be advanced in MF-fed infants and that testicular development may be slower in both MF and SF infants as compared with BF. There was no evidence that feeding SF exerts any estrogenic effects on reproductive organs studied., (Copyright 2010 Mosby, Inc. All rights reserved.)

The aim of this study was to assess the severity of any underlying malocclusion in subjects presenting for treatment of a palatally impacted canine (PIC) using a modification of the Dental Health Component (DHC) of the Index of Treatment Need (MIOTN), which does not factor in the impacted canine. The pre-treatment study models of 54 subjects who had previously undergone surgical exposure of a PIC, followed by fixed appliance orthodontic alignment, were scored independently by two examiners on two occasions using the MIOTN system. Unweighted kappa statistics revealed good intraoperator agreement for the two examiners and a moderate level of interexaminer agreement. Forty-six and 41 per cent of the sample still scored either an MIOTN grade 4 or 5 (i.e. a great or very great need of orthodontic treatment). However, 20 and 25 per cent of the subjects were graded with a MIOTN score of 1 or 2, indicating little or no need for treatment when the PIC was not taken into consideration. This finding emphasizes the importance of early diagnosis of an impacted canine and the need to institute interceptive measures where necessary, as up to 25 per cent of patients might otherwise require no other orthodontic treatment.

Killer lymphocytes recognize stress-activated NKG2D ligands on tumors. We examined NKG2D ligand expression in head and neck squamous cell carcinoma (HNSCC) cells and other cell lines. HNSCC cells typically expressed MHC class I chain-related gene A (MICA), MICB, UL16-binding protein (ULBP)2, and ULBP3, but they were uniformly negative for cell surface ULBP1 and ULBP4. We then studied how cancer treatments affected NKG2D ligand expression. NKG2D ligand expression was not changed by most cancer-relevant treatments. However, bortezomib and other proteasome inhibitor drugs with distinct mechanisms of action dramatically and specifically up-regulated HNSCC ULBP1 mRNA and cell surface protein. Proteasome inhibition also increased RNA for ULBP1 and other NKG2D ligands in nontransformed human keratinocytes. Proteasome inhibitor drugs increased ULBP1 transcription by acting at a site in the 522-bp ULBP1 promoter. Although the DNA damage response pathways mediated by ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) signaling had been reported to up-regulate NKG2D ligand expression, we found that ULBP1 up-regulation was not inhibited by caffeine and wortmannin, inhibitors of ATM/ATR signaling. ULBP1 expression in HNSCC cells was not increased by several ATM/ATR activating treatments, including bleomycin, cisplatin, aphidicolin, and hydroxyurea. Ionizing radiation caused ATM activation in HNSCC cells, but high-level ULBP1 expression was not induced by gamma radiation or UV radiation. Thus, ATM/ATR signaling was neither necessary nor sufficient for high-level ULBP1 expression in human HNSCC cell lines and could not account for the proteasome effect. The selective induction of ULBP1 expression by proteasome inhibitor drugs, along with variable NKG2D ligand expression by human tumor cells, indicates that NKG2D ligand genes are independently regulated.

Context: Nonradiographic tests to identify fractures rely on a patient's report of increased pain at the site of injury. These tests can be misleading and produce false-positive or false-negative results because of differences in pain tolerance. A painless technique using a tuning fork and stethoscope to detect fractures has undergone limited review in the athletic training literature., Objective: To determine if the use of a 128-Hz vibrating tuning fork and stethoscope were effective in identifying fractures., Design: Cross-sectional study., Setting: University athletic training room or local orthopaedic center when fractures were suspected., Patients or Other Participants: A total of 37 patients (19 males, 18 females) volunteered., Main Outcome Measure(s): A diminished or absent sound arising from the injured bone as compared with the uninjured bone represented a positive sign for a fracture. Radiographs interpreted by the attending orthopaedic physician provided the standard for comparison of diagnostic findings., Results: Sensitivity was 0.83 (10:12), specificity was 0.80 (20:25), positive likelihood ratio was 4.2, negative likelihood ratio was 0.21, and diagnostic accuracy was 81% (30:37)., Conclusions: The tuning fork and stethoscope technique was an effective screening method for a variety of fractures.

The aim of this study was to determine which of two occlusal indices were the most appropriate for use in the assessment of orthognathic outcome. The indices used were the Peer Assessment Rating (PAR) Index and the Index of Treatment Complexity, Outcome, and Need (ICON). These indices were validated against the subjective assessments of treatment outcome and treatment improvement obtained from a panel of experienced orthodontic consultants. For the subjective assessment, intraexaminer agreement for ranking treatment outcome, from patient study models (30 models), was good. Interexaminer agreement for ranking treatment outcome, in the same way, was good or moderate. Intraexaminer agreement for ranking treatment improvement (30 start and finish pairs of models) was very good or good. Interexaminer agreement for ranking treatment improvement ranged from good to fair. All the patient study models were scored using PAR and ICON. The level of correlation between PAR and ICON scores of treatment outcome and the subjective ranking of treatment outcome was significant (P < 0.001). The level of correlation between PAR and ICON scores of treatment improvement and the subjective ranking of treatment improvement was also significant (P < 0.001). It is concluded that both PAR and ICON are suitable indices for assessing the clinical outcome of combined orthodontic treatment and orthognathic surgery.

Background: Patients with early stage nonsmall-cell lung cancer who have undergone complete resection have a recurrence rate of approximately 50%, predominately due to the development of systemic metastases. This study is a prospective analysis of the expression of seven serum protein markers of invasion and metastasis, collected preoperatively (baseline) and serially after resection, to determine the relationship between marker expression and recurrence., Methods: Serum was collected from 196 patients with clinical stage I nonsmall-cell lung cancer who underwent resection over a 5-year period (1996 to 2000). Samples were drawn before resection and 1, 4, 6, 12, 18, and 24 months postoperatively. All patients were followed for at least 24 months or until death. Serum protein levels of vascular endothelial growth factor, hepatocyte growth factor), E-selectin, CD44, basic fibroblast growth factor, urokinase plasminogen activator, and urokinase plasminogen activator receptor were determined using enzyme-linked immunosorbent assay., Results: To date, 73 patients (37%) have demonstrated recurrence. Baseline levels of only 1 marker (CD44) correlated with pathologic stage (p = 0.02). Analysis of the serial samples demonstrated that recurrence was predicted (before clinical or radiographic determination) by decreasing levels of E-selectin (p = 0.002), increasing levels of CD44 (p = 0.001), and increasing levels of urokinase plasminogen activator receptor (p = 0.03)., Conclusions: This study demonstrates the potential to predict recurrence after resection in patients with early-stage nonsmall-cell lung cancer using a panel of serum protein markers. Early identification of patients with recurrence may improve the efficacy of systemic therapy.

Mature human NK lymphocytes express the highly homologous killer Ig-like receptor (KIR) genes in a stochastic fashion, and KIR transcription precisely correlates with allele-specific DNA methylation. In this study, we demonstrate that CpG methylation of a minimal KIR promoter inhibited transcription. In human peripheral blood NK cells and long-term cell lines, expressed KIR genes were associated with a moderate level of acetylated histone H3 and H4 and trimethylated histone H3 lysine 4. Histone modifications were preferentially associated with the transcribed allele in NK cell lines with monoallelic KIR expression. Although reduced, a substantial amount of histone acetylation and H3 lysine 4 trimethylation also was associated with nonexpressed KIR genes. DNA hypomethylation correlated with increased chromatin accessibility, both in vitro and in vivo. Treatment of NK cell lines and developing NK cells with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, caused a dramatic increase in KIR RNA and protein expression, but little change in histone modification. Our findings suggest that KIR transcription is primarily controlled by DNA methylation.

Natural killer (NK) cells are essential for healthy aging. NK cell activation is controlled by MHC class I-specific CD94/NKG2 receptors and killer immunoglobulin-like receptors (KIR). To assess NK cytotoxic function in isolation from MHC receptor engagement, we measured the ability of purified NK cells to kill mouse P815 target cells in the presence of anti-CD16 mAb. CD16-mediated cytotoxicity did not change with age, indicating that NK activation and cytotoxic granule release remained functional. We then investigated MHC class I receptor expression on NK cells. There was an age related decrease in CD94 and NKG2A expression and a reciprocal age related increase in KIR expression. NKG2A expression also declined with age on CD56(+) T cells. CD94/NKG2A receptor function was proportional to expression, indicating that NK cell inhibitory signaling pathways were intact. NKG2A and KIR expression were complementary, suggesting that CD94/NKG2A function could substitute for inhibitory KIR function during polyclonal NK cell development in both young and elderly adults. The distinct roles of CD94/NKG2A and KIR receptors suggest that shifting MHC class I receptor expression patterns reflect age related changes in NK cell and CD56(+) T cell turnover and function in vivo.

Chronic distress has been associated with alterations in natural killer (NK) cell and T cell percentages and function. NK cells express inhibitory and stimulatory receptors that regulate cytotoxicity and cytokine secretion. T cells and T cells expressing CD56 (NKT cells) also express these NK-associated receptors, which are thought to serve the same function. The objective of this study was to examine the relationship between distress and expression of NK-associated receptors on NK cells, T cells, and NKT cells. Using multicolor flow cytometry and validated questionnaires, we studied twenty-nine healthy adults with a bimodal age spread. Whereas distress was related to significantly lower percentages of CD3(+) T cells, it was related to significantly higher percentages of NKT cells. Distress was associated with significantly higher percentages of T cells expressing NK-associated receptors including CD94 and KIR. In contrast, distress was associated with significantly lower percentages of NK cells bearing KIR (GL183) receptors. Our findings suggest a possible role for NK-associated receptors in distress-related alterations in lymphocyte maturation, trafficking, or activity.

Purpose: To assess the relationship between molecular markers associated with chemotherapy resistance and survival in esophageal cancer patients treated with trimodality therapy., Experimental Design: The original pretreatment formalin-fixed, paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 99 patients treated with concurrent cisplatin plus 5-fluorouracil plus 45 Gy radiation followed by resection at Duke University Medical Center (Durham, NC) from 1986 to 1997. cDNA was derived from the biopsy and analyzed to determine mRNA expression relative to an internal reference gene (beta-actin) using fluorescence-based, real-time reverse transcription-PCR. Possible markers of platinum chemotherapy association [glutathione S-transferase pi (GSTP1) and excision cross-complementing gene 1 (ERCC1)] and 5-fluorouracil association [thymidylate synthase 1 (TS1)] were measured., Results: Cox proportional hazards model revealed a significant inverse, linear effect for TS1 with respect to survival (P = 0.007). An inverse relationship between TS1 expression and treatment response was also detected (P < or = 0.001). Univariate analysis identified an association with decreased survival for GSTP1 > or = 3.0 (P = 0.05). In multivariate analyses, TS1 >6.0, ERCC1 >3, and GSTP1 >3 were statistically significant predictors of decreased survival (P = 0.007). Additionally, the presence of ERCC1 >3.0 or TS1 >6.0 was associated with an approximately 2-fold increase in the risk of cancer recurrence (P = 0.086 and 0.003, respectively)., Conclusion: The measurement of relative gene expression of molecular markers associated with chemoresistance in endoscopic esophageal tumor biopsies may be a useful tool in assessing outcome in patients with trimodality-treated esophageal cancer. These data should be validated further in larger prospective studies.

Introduction: The potential consequences of obesity in trauma patients are significant, yet incompletely defined by previous studies., Objectives: To evaluate the effect of obesity on morbidity and mortality among injured patients., Methods: Medical records of all trauma patients evaluated at an American College of Surgeons verified Level I trauma center over a 1-year period were retrospectively reviewed. Morbidity and mortality were assessed after patients were stratified according to body mass index (BMI=kilograms/meters) and injury severity score., Results: The mortality of patients with a BMI > or =35 (obese patients) was 10.7% versus 4.1% for patients with a BMI<35 (lean patients, p = 0.003). Nearly 27% of obese patients versus 17.6% of lean patients experienced one or more complications while in the hospital (p = 0.02)., Conclusions: Obese patients are significantly more likely than lean patients to experience complications and death after a traumatic event. This effect is enhanced with higher levels of injury.

Background: The long-term survival of patients with stage III non-small cell lung cancer treated with a combination of chemotherapy and radiation is 10% to 20%. Survival could potentially be increased and toxicity limited if one could identify patients most likely to respond to a particular treatment regimen. This project prospectively evaluated a panel of potential immunohistochemical markers of chemoresistance in a population of patients with pathology-confirmed stage III non-small cell lung cancer in order to determine the prognostic value of each marker in relation to response to chemotherapy or survival., Methods: Immunohistochemical staining was performed on histologically positive mediastinal nodal specimens obtained from 59 patients (mean age, 62 years; range, 41 to 79 years) without evidence of distant metastatic disease treated with navelbine-based chemotherapy and external beam radiation therapy between 1996 and 2001. Included were markers for apoptosis (p53, bcl-2), drug efflux/degradation (MDR, GST-pi), growth factors (EGFr, Her2-neu), and mismatch repair (hMLH1, hMSH2). After chemotherapy, patients underwent radiologic evaluation for response measured by standard criteria., Results: After a median 41 months of follow-up (range, 17 to 55 months), 43 patients had recurrent disease and 38 of these patients were dead of cancer (median cancer-free survival of 10 months and overall survival of 18 months). Patients who demonstrated a complete or partial response (n = 38) had a significantly improved survival (p = 0.002) compared with those with stable or progressive cancer (n = 21). Multivariable Cox step-wise regression analysis of marker expression associated overexpression of p53 and low expression of hMSH2 with poor treatment response and cancer death., Conclusions: These preliminary data suggest that marker expression may allow the separation of patients into low- and high-risk groups with respect to survival after combined navelbine-based chemotherapy and XRT. This could represent a novel method of selecting patients for a particular treatment regimen if these data are reproduced in a larger prospective trial.