Interprofessional obstetric simulation training improves postpartum haemorrhage management and decreases maternal morbidity: a before-and-after study.

OBJECTIVE: To determine the impact of the Obstetric Simulation Training and Teamwork (OB-STaT) curriculum on postpartum haemorrhage (PPH) rates and outcomes. DESIGN: Before-and-after study. SETTING: Maternity care hospitals within the USA. POPULATION: Patients who delivered between February 2018 and November 2019. METHODS: Interprofessional obstetric teamwork training (OB-STaT) conducted at each hospital. Electronic medical records for deliveries were reviewed for 6 months before and after conducting OB-STaT at participating hospitals. MAIN OUTCOME MEASURES: The PPH rate (blood loss of ≥1000 ml), uterotonic medications used, tranexamic acid use, blood product transfusion, hysterectomy, length of stay and composite maternal morbidity (postpartum haemorrhage, hysterectomy, transfusion of ≥4 units of blood products and intensive care unit admission for PPH). RESULTS: A total of 9980 deliveries were analysed: 5059 before and 4921 after OB-STaT. The PPH rates did not change significantly (5.48% before vs 5.14% after, p = 0.46). Composite maternal morbidity decreased significantly by 1.1% (6.35%-5.28%, p = 0.03), massive transfusions decreased by 57% (0.42%-0.18%, p = 0.04) and the mean postpartum length of stay decreased from 2.05 days (1.05 days SD) to 2.01 days (0.91 days SD) (p = 0.04). Following OB-STaT, haemorrhage medication use increased by 36% (14.8%-51.2%, p = 0.03), the use of tranexamic acid for PPH treatment almost doubled (2.7%-4.8%, p < 0.001) and the rate of hysterectomy significantly increased (0%-0.1%, p = 0.03). CONCLUSIONS: Although the PPH rates did not decrease, OB-STaT significantly improved maternal morbidity, decreased massive transfusions, and improved PPH management by increasing the utilization of uterotonic medications, tranexamic acid and hysterectomy.

Association of Pelvic Floor Disorders, Perceived Psychological Stress, and Military Service in U.S. Navy Servicewomen: A Cross-Sectional Survey.

IMPORTANCE: Pelvic floor disorders (PFDs) are linked to psychological stress and decreased work performance in civilian populations. Higher psychological stress is reported in female active-duty servicewomen (ADSW), which affects military readiness. OBJECTIVE: This study sought to associate PFDs, work-related challenges, and psychological stress in ADSW. STUDY DESIGN: We conducted a single-site, cross-sectional survey of ADSW seeking care in the urogynecology, family medicine, and women's health clinics between December 2018 and February 2020 using validated questionnaires to determine the prevalence of PFDs and the association with psychological stress, performance of military duties, and continued military service. RESULTS: One hundred seventy-eight U.S. Navy ADSW responded; most were seeking care for PFDs. The reported prevalence rates of PFDs were as follows: urinary incontinence, 53.7%; pelvic organ prolapse, 16.3%; fecal incontinence, 73.2%; and interstitial cystitis/bladder pain syndrome, 20.3%. Active-duty servicewomen with PFDs were more likely to have higher psychological stress scores (22.5 ± 3.7 vs 20.5 ± 4.2, P = 0.002) and body composition failures (22.0% vs 7.3%, P = 0.012), yet more strongly consider remaining on active service if they reported urinary incontinence (22.8% vs 1.8%) or interstitial cystitis/bladder pain syndrome (19.5% vs 1.8%; all P ≤ 0.001). No significant differences were noted in physical fitness failures or other military duties. CONCLUSIONS: For these U.S. Navy ADSW with PFDs, there was no significant difference in duty performance but reported psychological stress levels were higher. The presence of PFD was associated with women more strongly considering ongoing military service compared with other factors such as family, job, or career path.

Innovative Use of Cadavers in Perioperative Nursing Orientation.

The Periop 101 program administrator at a US Navy medical center worked with personnel in the facility's simulation and bioskills laboratories to develop an innovative perioperative nurse orientation curriculum that included the use of human cadavers during simulation activities. Participants were able to practice common perioperative nursing skills (eg, surgical skin antisepsis) on human cadavers rather than simulation manikins. The orientation program comprises two three-month phases. Participants were evaluated twice during phase 1: at the six-week mark and again six weeks later at the end of the phase. Using the Lasater Clinical Judgment Rubric, the administrator scored participants on their clinical judgment skills; results showed that mean scores increased for all learners between the two evaluation sessions. Practicing skills in a safe environment allows new staff members to learn without fear of causing accidental patient harm, and the additional use of cadavers further increased simulation fidelity and learner satisfaction.

Obstetric Simulation Training and Teamwork: Immediate Impact on Knowledge, Teamwork, and Adherence to Hemorrhage Protocols.

INTRODUCTION: The Obstetric Simulation Training and Teamwork (OB-STaT) curriculum was an in situ interprofessional program to provide standardized postpartum hemorrhage (PPH) simulation training throughout a health system to decrease PPH morbidity. In this study portion, investigators hypothesized that OB-STaT would increase: (a) team member knowledge in diagnosis and management of PPH, (b) teamwork, (c) adherence to established PPH protocols, and (d) patient satisfaction. METHODS: The OB-STaT was implemented at 8 US Navy hospitals between February 2018 and November 2019. Participant PPH treatment and maternal/neonatal resuscitation pretraining/posttraining knowledge was assessed via an 11-item test, whereas teamwork and standardized patient assessment were rated using validated Likert-type scales: the 15-item Clinical Teamwork Scale and 3-item Patient Perception Score, with item ranges of 0 to 10 and 0 to 5, respectively. Local PPH protocol adherence was assessed using role-specific checklists, with a potential maximum of 14 points (anesthesia/nursing) or 22 points (obstetrics). RESULTS: Fifty-four interprofessional teams participated. Obstetricians (trainees and attendings) demonstrated significantly improved knowledge test scores (8.33 ± 1.6 vs. 8.66 ± 1.5, P < 0.01). Between the 2 scenarios, overall mean Clinical Teamwork Scale scores improved significantly for all interprofessional teams (5.82 ± 2.0 vs. 7.25 ± 1.9, P < 0.01). Anesthesia, nursing, and obstetric subteams demonstrated significant increases in protocol adherence as measured by critical action scores (12.28 ± 1.7 vs. 13.56 ± 1.0, 12.43 ± 1.6 vs. 13.14 ± 1.3, and 18.14 ± 2.7 vs. 19.56 ± 2.1 respectively, all P < 0.02). Although overall standardized patient satisfaction did not significantly improve, scores for feeling well informed did (3.36 ± 1.0 vs. 3.76 ± 0.8, P < 0.01). CONCLUSIONS: The OB-STaT curriculum modestly improved participants' teamwork, communication, and protocol adherence during simulated PPH scenarios; OB-STaT may decrease PPH morbidity.

VIP152 is a selective CDK9 inhibitor with pre-clinical in vitro and in vivo efficacy in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in potency compared with other inhibitors currently in development for this target. VIP152 induced cell death in CLL cell lines and primary patient samples. Transcriptome analysis revealed inhibition of RNA degradation through the AU-Rich Element (ARE) dysregulation. Mechanistically, VIP152 inhibits the assembly of P-TEFb onto the transcription machinery and disturbs binding partners. Finally, immune competent mice engrafted with CLL-like cells of Eµ-MTCP1 over-expressing mice and treated with VIP152 demonstrated reduced disease burden and improvement in overall survival compared to vehicle-treated mice. These data suggest that VIP152 is a highly selective inhibitor of CDK9 that represents an attractive new therapy for CLL.

High-Fidelity Orthopaedic Surgical Skills Models and Resident Performance in the Surgical Treatment of Tibial Plateau Fractures.

The purpose of this study was to quantify the impact of low-fidelity simulation on resident surgical skills education. Fourteen orthopaedic surgery residents (PGY-1 through PGY-5) were separated into two, training-level-matched cohorts - an untrained control cohort (UCC) and a low-fidelity Sawbones training cohort (SAW). Together, both cohorts received didactic instruction on the soft-tissue approach, intra-operative reduction, internal-fixation, and surgical wound closure of Schatzker II tibial plateau fractures. The SAW cohort first rehearsed open-reduction, internal-fixation on radiopaque Sawbones models (Pacific Research Laboratories Inc. Vashon, WA). Both cohorts were then evaluated while performing the same procedure on high-fidelity cadaveric models (Rimasys GmbH Cologne, Germany). Surgical skill and knowledge were assessed using the objective structured assessment of technical skills (OSATS) tool, a written exam, and an after-action survey. There were no significant differences in OSATS scores or written exam scores between the two cohorts. A near-linear positive relationship (R2 = 0.9737) existed between training year and average overall OSATS score. All residents expressed a preference for surgical skills training with high-fidelity cadaveric models. The results of this study fail to demonstrate a training advantage of low-fidelity Sawbones models when surgical skill is measured on high-fidelity cadaveric models. Despite this, residents across both cohorts qualitatively felt the high-fidelity models offered a better educational opportunity for surgical practice than did the low-fidelity Sawbones models. (Journal of Surgical Orthopaedic Advances 31(2):109-112, 2022).

Prevalence of Pelvic Floor Disorders in United States Active-Duty Service Women Seeking Medical Care.

IMPORTANCE: In the United States, pelvic floor disorders affect 25% of women. Despite facing unique occupational risk factors that may increase the risk of pelvic floor disorders, there is little research on the prevalence of these disorders in active-duty service women. OBJECTIVES: This study sought to identify the prevalence of and risk factors for pelvic floor disorders in active-duty service women in the United States from diagnostic codes through service utilization. STUDY DESIGN: Utilizing the Military Health System Data Repository, a cross-sectional study was conducted of all active-duty service women in the United States Army, Air Force, Navy, and Marine Corps during fiscal years 2010 to 2019. RESULTS: This study identified 497,255 active-duty service women of whom 9.93% had pelvic floor disorders. Adjusted regression model analyses indicated increasing parity and body mass index significantly affect the risk of pelvic floor disorders. Active-duty women with 3 or more births were 3 times more likely to have pelvic floor disorders compared with the nulliparous group. Finally, subset analysis indicates the risk of pelvic floor disorders were increased 250% in obese women and decreased 20% for underweight women. The rate of pelvic floor disorders appears to be increasing among active-duty women. CONCLUSIONS: Active-duty service women have significantly lower rates of pelvic floor disorders compared with the general population, possibly due to the protective effects of improved weight management and physical fitness requirements for their job performance. However, pelvic floor disorders may be uptrending and need continued monitoring.

First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy.

PURPOSE: To report on the first-in-human phase I study of VIP152 (NCT02635672), a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor. PATIENTS AND METHODS: Adults with solid tumors or aggressive non-Hodgkin lymphoma who were refractory to or had exhausted all available therapies received VIP152 monotherapy as a 30-minute intravenous, once-weekly infusion, as escalating doses (5, 10, 15, 22.5, or 30 mg in 21-day cycles) until the MTD was determined. RESULTS: Thirty-seven patients received ≥ 1 VIP152 dose, with 30 mg identified as the MTD based on dose-limiting toxicity of grade 3/4 neutropenia. The most common adverse events were nausea and vomiting (75.7% and 56.8%, respectively), all of grade 1/2 severity. Of the most common events, grade 3/4 events occurring in > 1 patient were neutropenia (22%), anemia (11%), abdominal pain (8%), increased alkaline phosphatase (8%), and hyponatremia (8%). Day 1 exposure for the MTD exceeded the predicted minimum therapeutic exposure and reproducibly achieved maximal pathway modulation; no accumulation occurred after multiple doses. Seven of 30 patients with solid tumors had stable disease (including 9.5 and 16.8 months in individual patients with pancreatic cancer and salivary gland cancer, respectively), and 2 of 7 patients with high-grade B-cell lymphoma with MYC and BCL2/BCL6 translocations (HGL) achieved durable complete metabolic remission (ongoing at study discontinuation, after 3.7 and 2.3 years of treatment). CONCLUSIONS: VIP152 monotherapy, administered intravenously once weekly, demonstrated a favorable safety profile and evidence of clinical benefit in patients with advanced HGL and solid tumors.

Effectiveness of the Ophthalmological Training Component of the STOMP (Simulation Training for Operational Medical Providers) Curriculum.

INTRODUCTION: Simulation has been used in medicine to train clinicians to manage a variety of clinical scenarios. A key adaptation of the use of simulation in military healthcare occurred in 2015 with the development of the STOMP (Simulation Training for Operational Medical Providers) curriculum, a specific curriculum designed for the intern (PGY-1) trained physicians being sent into the military to practice primary care. Despite showing the curriculum's influence on self-perceived comfort scores, no study has determined whether simulation is an effective means of improving general medical officer (GMO) physicians' skills compared to other traditional styles of education. Specifically, this study sought to determine whether simulation-based education (SBE) of ophthalmologic skills improves GMO physicians' clinical performance, as compared to traditional didactic-based instruction. METHODS: The study, conducted at Naval Medical Center Portsmouth, included GMO physicians who were enrolled in the 2019 STOMP class. Following a brief overview of the study, GMO physicians who elected to participate in the study were randomized to either SBE or lecture-based training for three commonly used ophthalmological procedures: slit lamp exam, tonometry, and corneal foreign body removal. After completing the simulation and lecture-based education training sessions, participants' procedural performance was evaluated utilizing a locally developed performance checklist, and completion time for each of the three procedures was recorded. Data were analyzed using the t-test and Mann-Whitney test. A significance level of 0.05 was considered to be statistically significant. RESULTS: Of the 50 consented participants, 46 completed the study. The mean overall completion scores for the performance checklists were significantly higher for the SBE group (n=26) compared to the lecture group (n=20) [80% (95% CI 78-82%) vs 41% (95% CI 35-47%), respectively]. Time to completion of the individual tasks was also significantly shorter for the SBE group compared to the lecture group (with mean differences ranging from 27 to 126 seconds, all p<.05). CONCLUSIONS: Simulation-based training appeared to be more effective at teaching three ophthalmological procedures (slit lamp exam, tonometry, and corneal foreign body removal) to GMO physicians compared to didactic-based instruction alone.

An Innovative Simulation Curriculum to Train General Surgery Residents and Medical Students on Four Commonly Encountered Obstetric and Gynecologic Procedures.

INTRODUCTION: Lack of obstetric and gynecologic (OBGYN) procedure exposure during general surgery residency was recognized as a training gap for military general surgery residents by U.S. Navy trauma and general surgeons serving as simulation leads for the Naval Medical Center Portsmouth general surgery resident program. Program faculty requested the authors develop and implement a recurring simulation curriculum to address this training gap. The primary goal of the simulation curriculum was to increase exposure to and confidence in performing four commonly encountered OBGYN procedures in a deployed setting: spontaneous vaginal delivery (SVD), Bartholin's cyst incision and drainage with Word catheter placement, cesarean delivery, and total abdominal hysterectomy (TAH). We hypothesized that trainees exposed to the new simulation curriculum would demonstrate an increase in knowledge and confidence in these four commonly encountered OBGYN procedures. MATERIALS AND METHODS: The study utilized a pre- and postdesign to determine the efficacy of a newly developed simulation curriculum as measured by participants' knowledge and confidence levels. The annual curriculum was 4 hours in duration and included a targeted lecture followed by the administration of the four OBGYN simulation skills stations: SVD, Bartholin's, cesarean delivery, and total abdominal hysterectomy. Proctors for the simulation stations consisted of OBGYN teaching faculty who had at least 5 years of clinical teaching experience and were experienced simulation instructors. Precourse and postcourse knowledge and confidence were self-rated on a 5-point Likert scale. The learners rated the course using the Simulation Design Scale. Likert scale data were analyzed using the paired Wilcoxon rank sum test. Descriptive statistics were reported for the Simulation Design Scale. P < 0.05 was considered to be statistically significant. This project was classified as nonhuman subjects' research by the Naval Medical Center Portsmouth Institutional Review Board. RESULTS: Over the 2 years since curriculum implementation, 34 trainees participated in the curriculum; no trainees have had the curriculum twice. All trainees confirmed training gaps on baseline self-assessment of knowledge and confidence of all four OBGYN procedures with the most confidence reported for SVD (2.83 mean). Self-rated knowledge and confidence levels improved significantly in all four of the simulated procedures for all 34 participants (P < 0.001). Postcurricular surveys (82% response rate, 28/34) indicated a high satisfaction with all areas of the simulation training (4.74/5.0). CONCLUSIONS: The implemented curriculum increased general surgery trainees' knowledge and confidence in four commonly encountered OBGYN procedures and demonstrated a high level of learner satisfaction and sustainability. The curriculum exhibits high educational impact and could be a valuable adjunctive training for other non-OBGYN physicians who may need to provide OBGYN care in military environments.

Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse.

OBJECTIVE: The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older. METHODS: This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis. RESULTS: A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status. CONCLUSIONS: Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.

Attendance and Quality and Quantity of Research Presentations at an Obstetrics and Gynecology Regional Meeting Pre- and Postchanges in Federal Funding.

INTRODUCTION: Participating in scientific meetings offers value to physician trainees and faculty. In 2012, the U.S. Government (including the Department of Defense) instituted restrictions on conference travel, requiring central approval to attend. Hence, our objective was to determine the academic impact of research presented at the American College of Obstetricians and Gynecologists (ACOG) Armed Forces District Meeting and the effect of this federally mandated policy change on attendance and the quality and quantity of research. MATERIALS AND METHODS: Attendance logs and meeting programs were reviewed for the 3 years immediately before and after institution of travel regulations. A PubMed search of each abstract was performed to determine if it resulted in publication and the mean duration in months from presentation to publication was calculated and compared between oral and poster presentations. The top journals accepting manuscripts were noted along with the corresponding impact factor. RESULTS: The overall meeting publication rate was 22%. Oral presentations were significantly more likely than posters to achieve publication (P < 0.001). Following implementation of travel regulations, mean faculty attendance declined from 130 per year to 105 (P < 0.05). Declines in resident attendance and publication rates were not statistically significant. The top journals publishing investigations included Obstetrics and Gynecology (n = 15), Military Medicine (n = 12), and Fertility and Sterility and Gynecologic Oncology (tied, both n = 11). CONCLUSION: Approximately one in five presentations at the ACOG Armed Forces District Meeting are published, many in high impact journals within the specialty. Implementation of stricter travel regulations adversely impacted faculty physician attendance, but not trainee participation or the publication rate.

In-situ Interprofessional Perinatal Drills: The Impact of a Structured Debrief on Maximizing Training While Sensing Patient Safety Threats.

Introduction In-situ interprofessional emergency team training improves participants' with confidence and knowledge and identifies latent safety threats. This study examined the impact of a structured debrief on an interprofessional perinatal team's ability to identify latent safety threats and assess competency in managing perinatal emergencies. It was hypothesized that latent safety threats would be reduced and checklist compliance would increase during subsequent in-situ perinatal team training. Methods Two in-situ training sessions were held six months apart. The perinatal emergency response team provided care for a standardized patient with preterm twin gestation. Each session included off-ward delivery and resuscitation of the first infant, transportation to appropriate inpatient units, cesarean delivery, and resuscitation of the second twin. Postpartum hemorrhage ensued, requiring massive transfusion protocol activation. Medical experts assessed team performance with critical action checklists. A structured debrief identified latent safety threats, developed action plans, and reviewed checklist compliance. Checklist compliance rates were analyzed using a z-ratio test. Results The first training session: seven teams (75 staff) completed 75% (292/391) critical action checklist items and identified 34 latent safety threats. Second training session: four teams (45 staff) completed 89% (94/106) critical action checklist items. Ten latent safety threats were mitigated during the second session. Utilizing a z-ratio, a significant difference was detected between the overall checklist compliance rates of the two sessions, z = -3.069, p = .002. Post-hoc power calculation was <10%. Conclusions In-situ interprofessional perinatal emergency team training is feasible, identifies latent patient safety threats, and may improve team competency.

Simulation Training for Operational Medicine Providers (STOMP): Impact of a Comprehensive Skills-Based Curriculum for Military General Medical Officers.

INTRODUCTION: A standardized training curriculum designed for general medical officers (GMO) titled Simulation Training for Operational Medicine Providers (STOMP) was recently developed to educate and improve GMOs' procedural skills through directed feedback prior to assuming duties in an operational environment. This study aimed to determine the impact this novel curriculum had on GMOs'confidence levels in 21 core privileges covering eight different subspecialties while stationed at Naval Medical Center Portsmouth (NMCP). MATERIALS AND METHODS: A cohort study from 2015 to 2017 was designed to address our specific aim to examine if the implementation of the STOMP curriculum increased GMOs' confidence levels. Fifty-seven participants enrolled in the study. The GMO case group completed the STOMP curriculum (n = 22), while the control or GMO self-study group (n = 35) did not complete the curriculum. Six months after starting clinical practice at NMCP, both groups completed an online survey that assessed their confidence level in performing each core privilege using a 5-point Likert scale. Scores were analyzed using a Wilcoxon Mann-Whitney test. Research data were derived from an approved Naval Medical Center, Portsmouth, Virginia IRB, protocol number: NMCP.2016.0010. RESULTS: Participants demonstrated a statistically significant increase in self-rated confidence scores (p < 0.05) in nine core privilege skills: punch biopsy, shave biopsy, excisional biopsy, removal of otic foreign body, removal of nasal foreign body, removal of ocular foreign body, tonometry, incision and drainage of a thrombosed hemorrhoid, and reduction of simple closed fractures and dislocations. CONCLUSIONS: These findings suggest that a novel and recently developed standardized simulation training curriculum entitled STOMP improves the confidence levels of early career physicians' in several primary care procedural skills and is an ideal adjunct to traditional lecture-based teaching prior to independent practice in a primary care environment.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis. METHODS: The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Patients (aged ≥18 years) had active moderate-to-severe psoriatic arthritis (defined as at least five swollen joints and at least five tender joints) fulfilling Classification for psoriatic arthritis (CASPAR) criteria, active or a documented history of plaque psoriasis, and an insufficient response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Patients continued to take csDMARDs during the study if they had received this treatment for at least 12 weeks before screening and were on a stable dose for at least 4 weeks before baseline. Using an interactive web-based system, we randomly allocated patients (1:1) to filgotinib 200 mg or placebo orally once daily for 16 weeks (stratified by current use of csDMARDs and previous use of anti-tumour necrosis factor). Patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16 in the full analysis set (patients who received at least one dose of study drug), which was compared between groups with the Cochran-Mantel-Haenszel test and non-responder imputation method. This trial is registered with ClincalTrials.gov, number NCT03101670. FINDINGS: Between March 9, and Sept 27, 2017, 191 patients were screened and 131 were randomly allocated to treatment (65 to filgotinib and 66 to placebo). 60 (92%) patients in the filgotinib group and 64 (97%) patients in the placebo group completed the study; five patients (8%) in the filgotinib group and two patients (3%) in the placebo group discontinued treatment. 52 (80%) of 65 patients in the filgotinib group and 22 (33%) of 66 in the placebo group achieved ACR20 at week 16 (treatment difference 47% [95% CI 30·2-59·6], p<0·0001). 37 (57%) patients who received filgotinib and 39 (59%) patients who received placebo had at least one treatment-emergent adverse event. Six participants had an event that was grade 3 or worse. The most common events were nasopharyngitis and headache, occurring at similar proportions in each group. One serious treatment-emergent adverse event was reported in each group (pneumonia and hip fracture after a fall), one of which (pneumonia) was fatal in the filgotinib group. INTERPRETATION: Filgotinib is efficacious for the treatment of active psoriatic arthritis, and no new safety signals were identified. FUNDING: Galapagos and Gilead Sciences.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. METHODS: In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270. FINDINGS: Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was -1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, with a least squares mean difference between groups of -0·85 (95% CI -1·17 to -0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients in each group, the most common being nasopharyngitis (in two patients in the filgotinib group and in four patients in the placebo group). Treatment-emergent adverse events led to permanent treatment discontinuation in two patients (a case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in the placebo group). No deaths were reported during the study. INTERPRETATION: Filgotinib is efficacious and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs. Further investigation of filgotinib for ankylosing spondylitis is warranted. FUNDING: Galapagos and Gilead Sciences.

Simulation Training for Operational Medicine Providers (STOMP): Design and Implementation of a Novel Comprehensive Skills-Based Curriculum for Military General Medical Officers.

Background: Fifty percent of graduating U.S. Navy post-graduate year (PGY)-1 physicians will practice in the operational environment before returning to residency training. However, current internship structure is less rotational and focuses more on specialty-specific training. Therefore, these physicians may not be fully prepared for this primary care role. Methods: Based on the U.S. Navy privileges for General Medical Officers, a comprehensive didactic and simulation curriculum was developed. Twenty-three procedural skill competencies (SK) and five validated standardized patient (SP) scenarios were identified. During the SK portion, learners reviewed instructional videos, read reference materials, and practiced with partial task trainers before small-group sessions with subject matter experts (SME). Separate SP round-robin sessions were conducted and feedback provided by SMEs and SPs. Learners demonstrated competency or were remediated. Results: One hundred and three PGY-1 trainees participated over 2 yr. All trainees met requirements during the SK phase. During the SP phase, seven learners required remediation. All learners ultimately met requirements for privileging. Conclusion: The Simulation Training for Operational Medicine Providers curriculum for future General Medical Officers is an effective tool for primary care skill training and credentialing. Plans for export to other Graduate Medical Education sites are underway and further evaluation of skills retention is warranted.

Complications of Sling Surgery for Stress Urinary Incontinence Among Female Military Beneficiaries.

BACKGROUND: Prior studies of complications after sling surgery excluded the large number of women in military treatment facilities (MTFs). OBJECTIVE: To characterize the postoperative complication rates after sling surgery for Stress urinary incontinence (SUI) within MTFs in the United States. MATERIALS AND METHODS: Retrospective cohort study of women aged 18 and older, with SUI, and who underwent either an outpatient or inpatient mid-urethral sling placement for SUI in any MTF in the United States between January 1, 2011 and December 31, 2012. RESULTS: During the study period, 348 surgeons performed 1632 slings. The average patient age was 47.2 years, and 22.4% of the patients had a concomitant pelvic organ prolapse procedure. Overall, 45.5% of subjects had at least one postoperative complication. Of the specific complications, urologic infectious complications were the most frequent, occurring in 25.2% of patients. Overall, only 0.9% of patients underwent a repeat incontinence procedure. In multivariate analyses, concomitant pelvic organ procedure was associated with an increased risk of bladder outlet obstruction and noninfectious urologic complications. Those with a Charlson comorbidity index score of 1 or more were more likely to have an infectious complication and a new diagnosis of pelvic pain. Women older than the median age were less likely than those below to experience treatment failure and a new diagnosis of pelvic pain. CONCLUSIONS: The population of women with SUI undergoing sling surgery at MTFs is a young population with postoperative complication rates lower than previously reported. However, the absolute overall complication rate is still high, specifically related to urinary tract infections, suggesting that significant opportunities exist for quality improvement.

Military Surgeon Volume and Stress Incontinence Surgery Complications: A Retrospective Cohort Study.

STUDY OBJECTIVE: To compare 12-month postoperative complication rates in women who underwent sling procedures by high-volume versus low-volume surgeons at US military treatment facilities (MTFs). DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: US MTFs. PATIENTS: Female military beneficiaries enrolled in TRICARE. INTERVENTIONS: Sling surgery for stress urinary incontinence between January 1, 2011 and December 31, 2012. MEASUREMENTS AND MAIN RESULTS: The primary exposure was surgeon volume (high vs low). Surgeon volume was categorized as high or low based on the number of slings performed in the previous 2 years at US MTFs (January 1, 2009 to December 31, 2010). The primary outcome was a composite variable indicating at least 1 postoperative complication within 12 months. We used International Classification of Diseases, 9th revision and Current Procedural Terminology codes to identify postoperative complications that occurred in the 12 months after the index sling procedure. During the study period 348 gynecologic and urologic surgeons performed 1632 slings. The average patient age was 47.2 years. Based on our data distribution we classified surgeons as high volume (>12 slings/2 years) or low volume (<4 slings/2 years). High-volume surgeons operated on patients who were older, more likely to have comorbidities, and more likely to receive concomitant prolapse surgery. Using a cluster analysis the overall likelihood of at least 1 postoperative complication in 12 months for high-volume versus low-volume surgeons was 48.4% versus 42.2% (adjusted odds ratio, 1.24; 95% confidence interval, .99-1.54; p = .06). There were no differences between high- and low-volume surgeons in the rate of almost all other postoperative complications. CONCLUSION: No significant differences in 12-month complication rates after sling surgery, stratified by surgeon volume, were seen in a setting of overall low-volume military surgeons.