Medical Students' Perceptions of Orthopedics as a Career for Women.

OBJECTIVES: To determine potential factors influencing female medical students' interest and subsequent application to orthopedics, and to evaluate female and male medical students' perceptions of women in the field of orthopedics. METHODS: An institutional review board-approved survey was distributed in March 2020 and subsequently in April 2022 to medical students in the classes of 2023 and 2024 at the University of Alabama at Birmingham Heersink School of Medicine. Study data were collected and managed using REDCap electronic data capture. An e-mail link to the REDCap survey was sent to students across the southeast region of the United States, followed by three reminder e-mails. All 25 allopathic medical schools in the southeastern United States with an Orthopedics Interest Group listed on their institution's Web site were invited to participate in the study. Nine Orthopedics Interest Group leaders interested in participating were asked to provide the researchers with a list of fourth-year medical students who attended an event hosted by that group (215). A total of 39 respondents who completed the survey were included in this study. RESULTS: Overall, the majority of students (n = 35, 90%) believed that women faced more barriers to a career in orthopedics than did men. The most significant barriers to women entering the field of orthopedics were the perceived expectations of an orthopedic surgeon (n = 34, 87%), difficulty balancing career and family (n = 28, 72%), and demanding schedule (n = 13, 33%). CONCLUSIONS: This study demonstrates that both male and female medical students believe there are significant additional barriers to success for women in the field. Study participants report that expectations set by physicians, other healthcare professionals, and patients contribute to creating greater barriers that deter medical students interested in orthopedics from ultimately applying to the specialty.

Macrocyclic Peptidomimetic Plasmepsin X Inhibitors with Potent In Vitro and In Vivo Antimalarial Activity.

The Plasmodium falciparum aspartic protease plasmepsin X (PMX) is essential for the egress of invasive merozoite forms of the parasite. PMX has therefore emerged as a new potential antimalarial target. Building on peptidic amino alcohols originating from a phenotypic screening hit, we have here developed a series of macrocyclic analogues as PMX inhibitors. Incorporation of an extended linker between the S1 phenyl group and S3 amide led to a lead compound that displayed a 10-fold improved PMX inhibitory potency and a 3-fold improved half-life in microsomal stability assays compared to the acyclic analogue. The lead compound was also the most potent of the new macrocyclic compounds in in vitro parasite growth inhibition. Inhibitor 7k cleared blood-stage P. falciparum in a dose-dependent manner when administered orally to infected humanized mice. Consequently, lead compound 7k represents a promising orally bioavailable molecule for further development as a PMX-targeting antimalarial drug.

Provider beliefs about the ideal design of an opioid deprescribing and substitution intervention for older adults.

PURPOSE: Opportunities exist to meaningfully reduce suboptimal prescription opioid use among older adults. Deprescribing is one possible approach to reducing suboptimal use. Appropriate interventions should outline how to carefully taper opioids, closely monitor adverse events, substitute viable alternative and affordable nonopioid pain treatments, and initiate medications for opioid use disorder to properly manage use disorders, as needed. We sought to document and understand provider perceptions to begin developing effective and safe opioid deprescribing interventions. METHODS: We conducted 3 semistructured focus groups that covered topics such as participant perspectives on opioid deprescribing in older adults, how to design an ideal intervention, and how to identify potential barriers or facilitators in implementing an intervention. Focus group transcripts were double coded and qualitatively analyzed to identify overarching themes. RESULTS: Healthcare providers (n = 17), including physicians, pharmacists, nurses, social workers, and administrative staff, participated in 3 focus groups. We identified 4 key themes: (1) involve pharmacists in deprescribing and empower them as leaders of an opioid deprescribing service; (2) ensure tight integration and close collaboration throughout the deprescribing process from the inpatient to outpatient settings; (3) more expansive inclusion criteria than age alone; and (4) provision of access to alternative pharmacological and nonpharmacological pain management modalities to patients. CONCLUSION: Our findings, which highlight various healthcare provider beliefs about opioid deprescribing interventions, are expected to serve as a framework for other organizations to develop and implement interventions. Future studies should incorporate patients' and family caregivers' perspectives.

A Plausible Pipeline to Diversifying Orthopaedics: Premedical Programming.

OBJECTIVE: To determine whether premedical programming can address the interest level and perception of barriers to women in orthopaedics held by female high school and medical students. DESIGN: A thirteen-question paper-based survey was distributed among the high school and medical school participants prior to the January 2020 Perry Outreach Program and Medical Student Outreach Program. After a day of participation in mock procedures and speaker sessions, participants subsequently completed another survey of seven-questions. SETTING: The Perry Outreach Program and Medical Student Outreach Program were conducted at the University of Alabama at Birmingham campus. PARTICIPANTS: Participants consisted of high school and medical school women hailing from the Birmingham metropolitan area, who had signed up for the Perry programs via email, outreach to local high schools, and social media interest pages. Participant sampling was stratified by race and level of education (high school vs. medical school). RESULTS: A total of 36 women, 18 high school and 18 medical school, attended the Perry Initiative events and responded to the pre-event and post-event surveys. Before the Perry Initiative programs, all participants felt women faced more barriers than men in pursuing a career in orthopaedics. Participation in the Perry Initiative event increased average interest in orthopaedics by 28% among high school and 11% among medical school students. CONCLUSIONS: Prior to the Perry Initiative, 31% percent of the total attendees reported knowing a female orthopaedist. The Perry Initiative improved perceptions of both high school and medical students regarding the ability of women to have a work/life balance, family life, and children during orthopaedics residency. Medical student participation in the events led to a decreased belief in barriers regarding schedule, family life, perceptions of an orthopaedic surgeon, and perceptions of peers within healthcare setting.

Effects from disruption of mitochondrial electron transport chain function on bull sperm motility.

Sperm mitochondrial function is essential for normal physiology and fertility, but the importance of mitochondrial activity to support specific sperm functions, such as motility, varies between species. It was previously believed that mitochondrial function was not necessary for bull sperm motility [1]; however, this theory is contradicted by recently reported findings that the upper fraction of bull sperm swim-up preparations had both high motility and elevated mitochondrial oxygen consumption rates [2]. The objective of this study was to investigate the relationship between mitochondrial function and motility in bull sperm. We hypothesized that sperm motility would be positively correlated with mitochondrial oxygen consumption (MITOX) but unaffected by pharmacological inhibition of electron transport chain (ETC) activity. This was accomplished by monitoring both mitochondrial oxygen consumption and motility parameters in the presence of mitochondrial effector drug treatments. Duplicate ejaculates were collected by electroejaculation from Black Angus bulls (n = 4). Oxygen consumption, as % air saturation (pO2; oxygen partial pressure), over time was monitored in the presence of 5 drug treatments: vehicle control, FCCP, Antimycin (ANTI), Oligomycin (Oligo), and FCCP + Oligomycin (FCCP + OLIGO). Duplicate aliquots were prepared for concurrent motility assessment by computer-assisted sperm analysis (CASA) at 6 and 30 min post-treatment (t6 and t30). The impact of treatments on pO2 (in % air saturation) over time were assessed by generalized linear mixed effects modeling (GLMM) which was also used to test for differences in average motility across treatment conditions and time points (t6 and t30). Pearson product-moment correlation was used to investigate relationships between oxygen consumption and motility parameters. Overall, pO2 differed over time between treatment conditions (p < 0.0001). When compared to the vehicle treatment, ANTI and OLIGO significantly inhibited oxygen consumption (p < 0.05, adjusted), and FCCP stimulated a marked increase in oxygen consumption. No significant differences in motility over time were observed between treatments, so comparison of motility parameters between treatment conditions was performed with pooled timepoints. Motility parameters were only observed to differ significantly from the vehicle with ANTI Treatment, for which significant decreases in numerous parameters, including total motility (p = 0.007), progressive motility (p = 0.01), DAP (p = 0.01), VAP (p = 0.01) and VSL (p = 0.02) were identified. For the vehicle treatment, correlational analysis did not reveal any significant correlations between pO2 and any motility parameters at t6; however, several significant correlations were identified at t30. Mean pO2 was negatively correlated with local motility (p < 0.01) and positively correlated with DCL, DAP, and VCL (p < 0.05). Results from this study suggest that bovine sperm motility is impacted by mitochondrial functionality, with ETC inhibition by ANTI causing significant reduction in motility parameters. This study also demonstrates the use of a new technology for the assessment of bovine sperm mitochondrial function. This modality for evaluation of bull sperm mitochondrial function will inform future efforts to understand bull sperm function and fertility and aid investigations into toxicological agents.

The Correlation Between Altmetric Score and Traditional Bibliometrics in Orthopaedic Literature.

BACKGROUND: Clinicians and medical researchers increasingly turn to nonformal online platforms to promote research. Altmetric Attention Score (AAS) is a quantitative measurement of online influence of research in real time. The objective of this study is to determine if AAS correlates with traditional bibliometrics in the orthopaedic literature. MATERIALS AND METHODS: From the 15 orthopaedic journals with the highest impact factor, the 10 most cited articles from each journal were reviewed for 2014 -2017. For each article, AAS was collected using the Altmetric Bookmarklet application and citation count from SCOPUS. Journal impact factor was recorded using Journal Citation Reports. Statistical analysis included Pearson's and Spearman's correlation coefficients. RESULTS: A total of 600 articles were analyzed. A significant positive correlation was found between citation count and AAS for 2014 (r = 0.3188, p < 0.0001), and no correlation for 2015 (r = 0.1504, P = 0.0653), 2016 (r = 0.0087, P = 0.9157), and 2017 (r = 0.0061, P = 0.9408). There was no significant correlation between impact factor and AAS in 2014 (r = 0.4312, P = 0.1085), 2015 (r = 0.3850, P = 0.1565), 2016 (r = 0.1460, P = 0.6035) and 2017 (r = 0.0451 P = 0.8732). CONCLUSIONS: AAS and traditional bibliometrics are currently not strongly correlated in orthopaedic literature. Citations take years to accumulate and AAS represents immediate influence of an article. An amalgamation of traditional bibliometrics and AAS may prove useful in determining the short- and long-term impact and influence of publications in orthopaedics.

Assessment of an iPad-based sperm motility analyzer for determination of canine sperm motility.

The objective of this study was to evaluate the repeatability and accuracy of canine sperm motility (total and progressive) assessment with a tablet-based Canine iSperm instrument compared to computer-assisted sperm analysis (CASA). The experiment used fresh and frozen/thawed canine semen samples for comparisons of semen analysis parameters (concentration, total motility, and progressive motility) between a CASA system, iSperm, and NucleoCounter SP-100 (concentration) instruments. Spearman's Rho correlational analysis was used to identify significant associations between motility assessment methods. Significant positive correlations were found between CASA assessment and iSperm for both progressive and total motility measurements. We also determined the coefficient of variation (CV) for repeatability of sample analysis for iSperm and CASA for fresh sperm, wherein each sample was assessed 10 times on both devices. For fresh and frozen-thawed samples, concentration assessment by iSperm showed high variability (CV= 19.9 ± 1.5%). For iSperm assessment of total and progressive motility, the CVs were 6.3 ± 0.5% and 10.7 ± 0.8%, respectively. The results indicate that the iSperm application offers an accurate and alternative measurement of motility to traditional CASA analysis, though caution should be taken when assessing concentration due to the high CV observed in this study.

Development and validation of the Tool for Pharmacists to Predict 30-day hospital readmission in patients with Heart Failure (ToPP-HF).

PURPOSE: Pharmacists are well positioned to provide transitions of care (TOC) services to patients with heart failure (HF); however, hospitalizations for patients with HF likely exceed the capacity of a TOC pharmacist. We developed and validated a tool to help pharmacists efficiently identify high-risk patients with HF and maximize their potential impact by intervening on patients at the highest risk for 30-day all-cause readmission. METHODS: We conducted a retrospective cohort study including adults with HF admitted to a health system between October 1, 2016, and October 31, 2019. We randomly divided the cohort into development (n = 2,114) and validation (n = 1,089) subcohorts. Nine models were applied to select the most important predictors of 30-day readmission. The final tool, called the Tool for Pharmacists to Predict 30-day hospital readmission in patients with Heart Failure (ToPP-HF) relied upon multivariable logistic regression. We assessed discriminative ability using the C statistic and calibration using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The risk of 30-day all-cause readmission was 15.7% (n = 331) and 18.8% (n = 205) in the development and validation subcohorts, respectively. The ToPP-HF tool included 13 variables: number of hospital admissions in previous 6 months; admission diagnosis of HF; number of scheduled medications; chronic obstructive pulmonary disease diagnosis; number of comorbidities; estimated glomerular filtration rate; hospital length of stay; left ventricular ejection fraction; critical care requirement; renin-angiotensin-aldosterone system inhibitor use; antiarrhythmic use; hypokalemia; and serum sodium. Discriminatory performance (C statistic of 0.69; 95% confidence interval [CI], 0.65-0.73) and calibration (Hosmer-Lemeshow P = 0.28) were good. CONCLUSIONS: The ToPP-HF performs well and can help pharmacists identify high-risk patients with HF most likely to benefit from TOC services.

Peptidic boronic acids are potent cell-permeable inhibitors of the malaria parasite egress serine protease SUB1.

Malaria is a devastating infectious disease, which causes over 400,000 deaths per annum and impacts the lives of nearly half the world's population. The causative agent, a protozoan parasite, replicates within red blood cells (RBCs), eventually destroying the cells in a lytic process called egress to release a new generation of parasites. These invade fresh RBCs to repeat the cycle. Egress is regulated by an essential parasite subtilisin-like serine protease called SUB1. Here, we describe the development and optimization of substrate-based peptidic boronic acids that inhibit Plasmodium falciparum SUB1 with low nanomolar potency. Structural optimization generated membrane-permeable, slow off-rate inhibitors that prevent Pfalciparum egress through direct inhibition of SUB1 activity and block parasite replication in vitro at submicromolar concentrations. Our results validate SUB1 as a potential target for a new class of antimalarial drugs designed to prevent parasite replication and disease progression.

Improving Pediatric Delirium Assessment Documentation and Implementation of a Nonpharmacologic Delirium Management Bundle in the Cardiovascular Intensive Care Unit.

BACKGROUND: Pediatric delirium is common, associated with negative patient outcomes, and infrequently assessed in the ICU. Locally, pediatric delirium assessments in the cardiac PICU were infrequently documented resulting in an initiative to increase assessment documentation and implement a nurse-driven management protocol, the Bundle to Eliminate Delirium (BED). METHODS: This was a nurse-driven, quality improvement project in an eleven-bed cardiac PICU at a large academic health care facility. A pre- and postimplementation survey evaluating delirium management perceptions, knowledge, and assessment barriers was emailed to 113 nurses. Nurses received education about general delirium principles and assessment followed by weekly emails that included delirium assessment documentation rates and targeted education. Subsequently, BED education was provided via email followed by BED implementation, inclusion of BED completion rates in weekly emails, and observational audits of BED implementation. FINDINGS: 1522 delirium assessment opportunities were evaluated. Assessment documentation increased by 33%. Nurses reported greater confidence in their ability to manage delirium (P < .05 for numerous aspects of delirium care) and were less likely to report 'positive delirium assessments not acted upon' as a barrier to delirium assessment. BED implementation was inconsistent. DISCUSSION: Nursing education and feedback can increase delirium assessment rates and confidence in management but the impact of BED on these outcomes is not clear. APPLICATION TO PRACTICE: Improvement in pediatric delirium care may be obtained through a nurse-driven quality improvement project but an interprofessional approach is needed for optimal management. More studies are needed to identify effective pediatric delirium management strategies such as the BED.

COVID-19 and Acute Cervical Spinal Cord Injury-Case Report of 2 Patients: Do We Need to Rethink Our Standard Treatment Strategy?

STUDY DESIGN: This was a case series. OBJECTIVE: The authors sought to examine the high-risk population of COVID-positive patients with acute cervical spinal cord injury (SCI) in a large level 1 trauma and tertiary referral center. SUMMARY OF BACKGROUND DATA: There are limited studies regarding the surgical management of patients with acute SCI in the setting of the recent coronavirus pandemic. METHODS: The authors describe the cases of 2 patients who died from COVID-related complications after acute cervical SCI. RESULTS: Patients with SCI are at increased risk of pulmonary complications. COVID-19 infection represents a double hit in this patient population, increasing potential morbidity and mortality in the perioperative time frame. Careful consideration must be made regarding the timing of potential surgical intervention in the treatment of acute SCI. CONCLUSIONS: Nationwide database of COVID-positive patients with acute spinal cord injury should be collected and analyzed to better understand how to manage acute SCI in the COVID-19 era. The authors recommend preoperative discussion in patients with acute cervical SCI with COVID-19, specifically emphasizing the increased risk of respiratory complications and mortality.

The high-value pharmacy enterprise framework: Advancing pharmacy practice in health systems through a consensus-based, strategic approach.

PURPOSE: The high-value pharmacy enterprise (HVPE) framework and constituent best practice consensus statements are presented, and the methods used to develop the framework's 8 domains are described. SUMMARY: A panel of pharmacy leaders used an evidence- and expert opinion-based approach to define core and aspirational elements of practice that should be established within contemporary health-system pharmacy enterprises by calendar year 2025. Eight domains of an HVPE were identified: Patient Care Services; Business Services; Ambulatory and Specialty Pharmacy Services; Inpatient Operations; Safety and Quality; Pharmacy Workforce; Information Technology, Data, and Information Management; and Leadership. Phase 1 of the project consisted of the development of draft practice statements, performance elements, and supporting evidence for each domain by panelists, followed by a phase 2 in-person meeting for review and development of consensus for statements and performance elements in each domain. During phase 3, the project cochairs and panelists finalized the domain drafts and incorporated them into a full technical report and this summary report. CONCLUSION: The HVPE framework is a strategic roadmap to advance pharmacy practice by ensuring safe, effective, and patient-centered medication management and business practices throughout the health-system pharmacy enterprise. Grounded in evidence and expert recommendations, the statements and associated performance elements can be used to identify strategic priorities to improve patient outcomes and add value within health systems.

Survival outcomes associated with corticosteroid use before chemoimmunotherapy in patients with advanced lung cancer.

BACKGROUND: How corticosteroid use affects treatment response to chemotherapy and immune-checkpoint inhibitors (CICPIs) remains unknown. We assessed how systemic corticosteroid exposure before CICPI modifies the effect of CICPI on outcomes among patients with metastatic non-small cell lung cancer (mNSCLC) or extensive-stage small-cell lung cancer (ES-SCLC). METHODS: We conducted a retrospective cohort study using electronic health records to examine patients with mNSCLC or ES-SCLC who received chemotherapy (CT) between 1st April 2015 and 31st January 2018 or CICPI between 1st February 2018 and 31st August 2019. We excluded those with an actionable driver mutation. Baseline corticosteroid use was defined as systemic corticosteroids within 28 days before the initiation of CT or CICPI, not including premedications. Coprimary outcomes included overall survival (OS), real-world progression (rwP), and real-world progression-free survival (rwPFS) in CICPI-treated corticosteroid users versus non-users. We used inverse probability of treatment weighting (IPW) to adjust for potential confounding. RESULTS: The cohort of 316 patients (median [interquartile range] age, 67 [61-73] years; 156 [49%] male) included 228 CT-treated and 88 CICPI-treated patients. After applying IPW, characteristics were well-balanced between the CT and CICPI groups, and steroid users and non-users. Using CT-treated steroid non-users as a common comparator, CICPI-treated steroid users were as likely as CICPI-treated steroid non-users to die (users IPW hazard ratio [HR] = 0.67, 95% CI = 0.35-1.28 versus non-users IPW-HR = 0.88, 95% C = I0.55-1.42; p = 0.49), have rwP (IPW-HR = 0.35, 95% C = I0.12-0.99 versus IPW-HR = 0.41, 95% C = I0.24-0.70; p = 0.77), or experience rwPFS (IPW-HR = 0.56, 95% C = I0.29-1.09 versus IPW-HR = 0.69, 95% CI0.46-1.03; p = 0.59). CONCLUSION: Corticosteroid use before CICPIs was not associated with worse outcomes, suggesting that corticosteroids should be used with CICPIs when indicated.

The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion.

Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either abortive invasion with rapid RBC lysis, or successful entry but developmental arrest. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for host RBC membrane sealing following parasite internalisation and for correct functioning of merozoite surface proteins.

Malaria kills or disables hundreds of millions of people across the world, especially in developing economies. The most severe form of the disease is caused by Plasmodium falciparum, a single-cell parasite which, once inside a human host, forces its way into red blood cells to feed on a protein called haemoglobin. This invasion relies on P. falciparum being engulfed by the membrane of the red blood cell, which then seals off to form a compartment inside the cell where the parasite can feed and multiply. Invasion takes less than 30 seconds, and it involves P. falciparum losing the coat of proteins that covers its surface. An enzyme calls SUB2 cleaves or cuts off these proteins, but exactly why and how the shedding takes place during infection is still unclear. To investigate, Collins, Hackett et al. deactivated the gene which codes for SUB2, and examined how mutant P. falciparum would survive and multiply. Without the enzyme, the parasites failed to shed many of their proteins, including some that were not previously known to be removed by SUB2. The majority of the genetically modified parasites also failed to invade red blood cells. In particular, most of the host cells ruptured, suggesting that the protein coat needs to be discarded for the engulfing process to be completed properly. When the enzyme-free mutants did manage to make their way into a red blood cell, they starved to death because they could not digest haemoglobin. SUB2 and surface coat shedding therefore appears to be essential for the parasite to survive. P. falciparum is fast becoming resistant to the many drugs that exist to fight malaria. New treatments that target SUB2 may therefore help in combatting this deadly disease.

Mass Air Medical Repatriation of Coronavirus Disease 2019 Patients.

Recent coronavirus disease 2019 (COVID-19) events have presented challenges to health care systems worldwide. Air medical movement of individuals with potential infectious disease poses unique challenges and threats to crews and receiving personnel. The US Department of Health and Human Services air medical evacuation teams of the National Disaster Medical System directly supported 39 flights, moving over 2,000 individuals. Infection control precautions focused on source and engineering controls, personal protective equipment, safe work practices to limit contamination, and containment of the area of potential contamination. Source control to limit transmission distance was used by requiring all passengers to wear masks (surgical masks for persons under investigation and N95 for known positives). Engineering controls used plastic sheeting to segregate and treat patients who developed symptoms while airborne. Crews used Tyvek (Dupont Richmond, VA) suits with booties and a hood, a double layer of gloves, and either a powered air-purifying respirator or an N95 mask with a face shield. For those outside the 6-ft range, an N95 mask and gloves were worn. Safe work practices were used, which included mandatory aircraft surface decontamination, airflow exchanges, and designated lavatories. Although most patients transported were stable, to the best of our knowledge, this represents the largest repatriation of potentially contagious patients in history without infection of any transporting US Department of Health and Human Services air medical evacuation crews.

Comparing Treatment Response Between Older and Younger Patients with Chronic Hepatitis C Virus Infection on Direct-acting Antiviral Agents.

OBJECTIVE: To compare sustained virologic response 12 weeks post-treatment completion (SVR12) and patient characteristics for older versus younger patients with chronic hepatitis C virus infection (HCV) receiving direct-acting antiviral (DAA) agent therapy. METHODS: This retrospective cohort study included patients with chronic HCV who received DAA therapy, between 2015 and 2018, in the largest health system in Rhode Island (N=154). Patient characteristics, comorbid diagnoses, and SVR12 status were compared between older (aged ≥60 years) and younger (<60 years) adults using chi-squared tests. RESULTS: Overall, 94.1% (95% CI: 90.4-97.8) achieved SVR12; response rates were 91.8% (95% CI: 84.9-98.6) for older adults and 95.6% (95% CI: 91.5-99.8) for younger adults (p=0.51). CONCLUSIONS: Our findings refute the historical notion that older adults were a "difficult-to-treat" subpopulation for whom clinicians should expect less treatment success. This is no longer the case with DAA therapy.

Pharmacokinetics of flucytosine in a critically ill patient on continuous venovenous hemodiafiltration.

PURPOSE: To describe the pharmacokinetics of flucytosine in a critically ill patient undergoing continuous venovenous hemodiafiltration (CVVHDF) treated for cryptococcal meningitis. SUMMARY: A 20-year-old female weighing 93.4 kg with a body mass index of 34.3 kg/m2 with a past medical history of systemic lupus erythematous with diffuse proliferative lupus nephritis (class IV) was admitted to the hospital after several months of worsening dyspnea, fatigue, myalgia, vomiting, and diarrhea. The patient developed worsening renal function and volume overload requiring CVVHDF on hospital day 7. She was diagnosed with cryptococcal meningitis on hospital day 8, and flucytosine 2,500 mg enterally every 12 hours and liposomal amphotericin B 500 mg intravenously every 24 hours were initiated. Flucytosine serum concentrations were collected on day 4 of therapy, and pharmacokinetics were performed on 2 sequential levels. Pharmacokinetic calculations displayed an elimination rate constant of 0.0338 h-1, a volume of distribution between 0.42 and 0.43 L/kg, a half-life of 20.5 hours, and a total drug clearance between 1.32 and 1.36 L/h while on CVVHDF. The nonsequential levels displayed good correlation, and no further monitoring or dosage adjustment was required. The patient completed therapy, with clinical resolution of her infection, and no toxicities due to flucytosine were noted. CONCLUSION: Flucytosine dosed at 25 mg/kg of actual body weight every 12 hours during CVVHDF conferred therapeutic levels with no appreciable toxicities. Because of its narrow therapeutic index and risk of toxicity, additional pharmacokinetic studies are needed to determine optimal drug dosing of this medication in patients requiring renal replacement therapy.

Descriptive Epidemiology of Injuries in Professional Ultimate Frisbee Athletes.

CONTEXT: Injuries in professional ultimate Frisbee (ultimate) athletes have never been described. OBJECTIVE: To determine injury rates, profiles, and associated factors using the first injury-surveillance program for professional ultimate. DESIGN: Descriptive epidemiology study. SETTING: American Ultimate Disc League professional ultimate teams during the 2017 season. PATIENTS OR OTHER PARTICIPANTS: Sixteen all-male teams. MAIN OUTCOME MEASURE(S): Injury incidence rates (IRs) were calculated as injuries per 1000 athlete-exposures (AEs). Incidence rate ratios were determined to compare IRs with 95% confidence intervals, which were used to calculate differences. RESULTS: We observed 299 injuries over 8963 AEs for a total IR of 33.36 per 1000 AEs. Most injuries affected the lower extremity (72%). The most common injuries were thigh-muscle strains (12.7%) and ankle-ligament sprains (11.4%). Running was the most frequent injury mechanism (32%). Twenty-nine percent of injuries involved collisions; however, the concussion rate was low (IR = 0.22 per 1000 AEs). Injuries were more likely to occur during competition and in the second half of games. An artificial turf playing surface did not affect overall injury rates (Mantel-Haenszel incidence rate ratio = 1.28; 95% confidence interval = 0.99, 1.67). CONCLUSIONS: To our knowledge, this is the first epidemiologic study of professional ultimate injuries. Injury rates were comparable with those of similar collegiate- and professional-level sports.