Women's Sports Medicine Programs in the United States: an interdisciplinary approach to the care of girls and women.

Objectives: Multiple studies have shown that women are more susceptible to certain musculoskeletal (MSK) injuries than their male counterparts. In response to these identified differences, several institutions have established Women's Sports Medicine Programs (WSMPs). The purpose of this study was to determine the number of WSMPs and explore program characteristics such as geographic location, specialties represented, common conditions treated, program history, and patient population.Methods: An extensive internet search was conducted to identify WSMPs in the United States. The second part of this study involved a 13-question, anonymous, electronic survey that was distributed to the directors of identified WSMPs to gather further data. Descriptive statistics were used to analyze the data.Results: Nineteen WSMPs were identified and the majority have been in existence for 6 to 10 years (44.4%). The survey was delivered to 18 programs and 9 WSMP directors responded (50% response rate). The most commonly reported number of physicians, across all specialties, comprising the core network was two physicians (4 programs, 44.4%). Health care providers with fourteen different areas of specialization were identified across all programs. The most common conditions treated were patellofemoral pain syndrome (33.3%), stress fracture (33.3%), and ACL tear (22.2%). In 5 programs (55.5%), patients < 18 years of age accounted for less than 25% of total patients. Only 2 programs (22.2%) reported that >51% of patients were actively participating in sports.Conclusion: This study demonstrates that nineteen Women's Sports Medicine Programs have been established in the United States. These programs address conditions known to have a higher incidence in the active female population, however the WSMPs are not solely geared towards the treatment of active female athletes. The information provided in this study can serve as a guide for the development of future WSMPs, as well as, future research studies regarding WSMPs.

Outcomes in the Orthopaedic Sports Medicine Fellowship Match, 2010-2017.

BACKGROUND: Sports medicine is one of the most competitive fellowships in orthopaedic surgery. Despite its popularity, fellowship applicants have limited understanding of the orthopaedic sports medicine fellowship match process. PURPOSE: To define key outcomes in the orthopaedic sports medicine fellowship match, including the overall match rate, number of programs filled, and number of applicants ranked by programs that filled between 2010 and 2017. STUDY DESIGN: Cross-sectional study. METHODS: This study utilized data regarding the orthopaedic sports medicine fellowship match collected by the American Orthopaedic Society for Sports Medicine (AOSSM) from 2010 through 2017. Applicant data included number of applicants, number of matched and unmatched applicants, and percentage of applicants matching into their top choices. Fellowship program data included number of programs participating in the match and number of applicants ranked by filled and unfilled programs. RESULTS: Between 2010 and 2017, the mean number of orthopaedic sports medicine fellowship applicants was 244.8. On average, 92.0% of applicants matched into a fellowship program. The mean number of programs participating in the fellowship match was 92.9, with a mean of 219.9 accredited positions and 5.4 nonaccredited positions. Over the time period studied, a mean of 75.8% of programs matched all available positions. Programs that matched fully ranked 9.0 applicants per position, on average, compared with a mean of 6.5 applicants ranked per position among programs that did not fully match (P = .0016). CONCLUSION: From 2010 to 2017, the number of applicants, positions available, overall match rate, and number of programs participating in the orthopaedic sports medicine fellowship match have remained consistent. The mean number of applicants per position ranked by fully matched fellowship programs was 9.0 compared with a mean of 6.5 applicants per position ranked by programs that did not fully match. These data may be helpful as we look to the future of orthopaedic sports medicine fellowship positions and the match process. In addition, this study reveals characteristics that divide sports medicine fellowship programs that fully match from those that do not. Applicants and/or fellowship program directors may utilize this information to modify their approach to the match process going forward.

Accelerated induction regimens of TNF-alpha inhibitors in patients with inflammatory bowel disease: a scoping review protocol.

INTRODUCTION: Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat inflammatory bowel disease (IBD). In patients with IBD who are unresponsive to their first induction dose, the implementation of an 'accelerated' induction dose schedule (doses more frequent than recommended in product monographs) is becoming increasingly common. It is unclear whether this practice results in favourable patient outcomes, such as avoidance of surgery and disease remission. As such, there is a need to identify and map the current evidence base on accelerated induction schedules of these medications in the treatment of IBD. METHODS AND ANALYSIS: A scoping review will be employed to systematically identify and characterise the nature of scientific literature on accelerated induction regimens of TNF-alpha inhibitors. MEDLINE, Embase, International Pharmaceutical Abstracts and grey literature will be searched to identify relevant studies. The titles/abstracts of all records and full text of potentially relevant articles will be independently screened for inclusion by two reviewers. Data will be abstracted from included studies by one reviewer and verified for accuracy by another. The findings will be synthesised descriptively. ETHICS AND DISSEMINATION: We intend to report the findings of this scoping review in a peer-reviewed journal and a scientific conference. TRIAL REGISTRATION: This research was registered prospectively with the Open Science Framework (https://osf.io/z7n2d/).

A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease.

Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.

Disaster Impact on Impoverished Area of US: An Inter-Professional Mixed Method Study.

Introduction In the foothills of the Cumberland Mountains, in central Appalachia (a region that spans 13 states in the US), sits an economically distressed and rural community of the United States. Once a thriving coal-mining area, this region now is reported as one of the hardest places to live in the US. Southeastern Kentucky, located in a remote, rocky, mountainous area surrounded by rivers and valleys and prone to flooding, experienced a major flood in Spring 2013 causing significant damage to homes and critical infrastructure. Purpose Aims of the study were to: (1) identify and better understand the contextual variables compounding the impact of a disaster event that occurred in Spring 2013; (2) identify ways participants managed antecedent circumstances, risk, and protective factors to cope with disaster up to 12 months post-event; and (3) further determine implications for community-focused interventions that may enhance recovery for vulnerable populations to promote greater outcomes of adaptation, wellness, and readiness. METHODS: Using an ethnographic mixed-methods approach, an inter-collaborative team conducted face-to-face interviews with (N=12) Appalachian residents about their disaster experience, documented observations and visual assessment of need on an observation tool, and used photography depicting structural and environmental conditions. A Health and Emergency Preparedness Assessment Survey Tool was used to collect demographic, health, housing, environment, and disaster readiness assessment data. Community stakeholders facilitated purposeful sampling through coordination of scheduled home visits. RESULTS: Triangulation of all data sources provided evidence that the community had unique coping strategies related to faith and spirituality, cultural values and heritage, and social support to manage antecedent circumstances, risk, and protective factors during times of adversity that, in turn, enhanced resilience up to 12 months post-disaster. The community was found to have an innate capacity to persevere and utilize resources to manage and transcend adversity and restore equilibrium, which reflected components of resilience that deserve greater recognition and appreciation. CONCLUSION: Resilience is a foundational concept for disaster science. A model of resilience for the rural Appalachia community was developed to visually depict the encompassing element of community-based interventions that may enhance coping strategies, mitigate risk factors, integrate protective factors, and strengthen access. Community-based interventions are recommended to strengthen resilience, yielding improved outcomes of adaptation, health and wellness, and disaster readiness. Banks LH , Davenport LA , Hayes MH , McArthur MA , Toro SN , King CE , Vazirani HM . Disaster impact on impoverished area of US: an inter-professional mixed method study. Prehosp Disaster Med. 2016;31(6):583-592.

Fibroblast Growth Factor 21-Null Mice Do Not Exhibit an Impaired Response to Fasting.

Fibroblast growth factor 21 (FGF21) is a pleotropic metabolic regulator, expression of which is elevated during fasting. To this end, the precise role played by FGF21 in the biology of fasting has been the subject of several recent studies, which have demonstrated contributions to the regulation of both lipid and carbohydrate metabolism. In the present study, we compared wild-type (WT) and FGF21-null (FGF21KO) mice, demonstrating that, despite the significant induction of FGF21 during fasting in the WT animals, our strain of FGF21-null mice exhibits only limited impairments in their adaptation to nutrient deprivation. Specifically, fasted FGF21KO mice display a mild attenuation of gluconeogenic transcriptional induction in the liver accompanied by partially blunted glucose production in response to a pyruvate challenge. Furthermore, FGF21KO mice displayed only minor impairments in lipid metabolism in the fasted state, limited to accumulation of hepatic triglycerides and a reduction in expression of genes associated with fatty acid oxidation. To address the possibility of compensation to germline deletion of FGF21, we further interrogated the role of endogenous FGF21 via acute pharmacological blockade of FGF21 signaling. At the transcriptional level, we show that FGF21 signaling is required for full induction of gluconeogenic and oxidative genes in the liver. However, corroborating our findings in FGF21KO mice, pharmacological blockade of the FGF21 axis did not profoundly disrupt the physiological response to fasting. Taken as a whole, these data demonstrate that, while FGF21 is partially required for appropriate gene expression during the fed to fasted transition, its absence does not significantly impact the downstream physiology of the fasted state.

High incidence of triple negative breast cancers following pregnancy and an associated gene expression signature.

Breast cancer risk increases transiently in the period following pregnancy; pregnancy-associated breast cancers (PABC) are more aggressive than cases diagnosed in nulliparous women. We have previously reported that in the normal human breast pregnancy results in the upregulation of a number of inflammation related genes, suggesting a pro-tumorigenic environment as well as downregulation of ESR1 (ERα) and ERBB2 (HER2) and upregulation of ESR2 (ERß), suggesting a protective effect. In this study, we aimed to investigate the possibility of differential regulation of the same gene set modulated in the normal breast, in human breast tumors following pregnancy. Gene expression was measured by real-time PCR on tumor regions isolated by laser capture microdissection from paraffin sections. Immunohistochemistry was performed on tissue microarrays (TMA) for protein expression. Hierarchical clustering was performed using the average linkage method to determine coordinate expression of sets of genes. We find that breast cancers detected within 10 years following pregnancy display a different gene expression pattern than those detected in nulliparous breast cancer patients. The gene expression difference is mainly attributable to a triple negative (TNBC) subgroup found to be more frequent in PABCs up to 10 years following a pregnancy. We also show that protein and mRNA expression levels correlate in half of the proteins tested by TMA. Despite the fact that this is a small study of 53 patients, we identified a gene expression signature that is differentially expressed in pregnancy-associated TNBC.

Reporting Guidelines for Clinical Pharmacokinetic Studies: The ClinPK Statement.

BACKGROUND AND OBJECTIVE: Transparent reporting of all research is essential for assessing the validity of any study. Reporting guidelines are available and endorsed for many types of research but are lacking for clinical pharmacokinetic studies. Such tools promote the consistent reporting of a minimal set of information for end users, and facilitate knowledge translation of research. The objective of this study was to create a guideline to assist in the transparent and complete reporting of clinical pharmacokinetic studies. METHODS: Preliminary content to be considered was identified from a systematic search of the literature and regulatory documents. Stakeholders were identified to participate in a modified Delphi exercise and a virtual meeting to generate consensus for items considered essential in the reporting of clinical pharmacokinetic studies. The proposed checklist was pilot tested on 100 recently published clinical pharmacokinetic studies. Overall and itemized compliance with the proposed guidance was determined for each study. RESULTS: Sixty-eight stakeholders from nine countries consented to participate. Four rounds of a modified Delphi survey and a series of small virtual meetings were required to generate consensus for a 24-item checklist considered to be essential to the reporting of clinical pharmacokinetic studies. When applied to the 100 most recently published clinical pharmacokinetic studies, 45 were determined to be compliant with at least 80 % of the checklist items. Explanatory text was prepared using examples of compliant reporting from these and other relevant studies. CONCLUSIONS: The reader's ability to judge the validity of pharmacokinetic research can be greatly compromised by the incomplete reporting of study information. Using consensus methods, we have developed a tool to guide transparent and accurate reporting of clinical pharmacokinetic studies. Endorsement and implementation of these guidelines by researchers, clinicians and journals would promote more consistent reporting of these studies and allow for better assessment of utility for clinical applications.

Scurvy: a new problem for patients with chronic GVHD involving mucous membranes; an easy problem to resolve.

Vitamin C deficiency in developed countries is typically observed in patients with unique clinical conditions such as cystic fibrosis or anorexia nervosa, or in patients on long-term tube feeds. We report here a clinical observation in six pediatric and adolescent patients (median age 17.5 yr, range 9.8-23.5 yr) with chronic GVHD with mucous membrane involvement found to be vitamin C deficient. These patients' baseline serum vitamin C levels ranged from <0.12 to 0.94 mg/dL (normal value 0.20-1.90 mg/dL), with a mean level 0.56 ± 0.36 mg/dL and a median level 0.6 mg/dL. Among these patients, signs and symptoms of mucositis failed to respond to standard chronic GVHD therapy. After receiving treatment with 2000 mg of ascorbic acid by mouth, daily patients displayed increased serum vitamin C levels. Clinically, this correlated with a remarkable improvement in patients' mucositis and ability to eat.

Gene expression patterns in the human breast after pregnancy.

Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammation-associated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor alpha (ERalpha, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-beta (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk.

Early onset preeclampsia and second trimester serum markers.

OBJECTIVE: To examine serum markers measured in the second trimester to identify women who subsequently develop preeclampsia. METHODS: Clinically defined preeclampsia was confirmed in 45 women who had provided a serum sample as part of Down syndrome screening. Preeclampsia was categorized as mild or severe, as well as early (<32 weeks) or late onset. Each case was matched with five controls based on gestational age and date of serum collection. Stored sera were retrieved and tested for inhibin A, soluble vascular endothelial growth factor receptor 1 (sVEGF R1), placental growth factor (PlGF), and endoglin. Results were converted to multiples of the median (MoM) and compared in case and control pregnancies. Univariate analysis was used to identify the strongest markers, which were then used in a multivariate model. RESULTS: Inhibin A, PlGF, and endoglin were consistently associated with preeclampsia, especially for early onset disease. A multivariate model using the three markers could identify 50% of the pregnancies with early onset preeclampsia with a 2% false positive rate. CONCLUSION: The levels of inhibin A, PlGF, and endoglin in the second trimester can be combined using a predictive model to provide individualized risk estimates for early onset preeclampsia.