The Effects of Leadership Curricula With and Without Implicit Bias Training on Graduate Medical Education: A Multicenter Randomized Trial

Purpose: To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians. Method: This was a double-blind randomized controlled trial among obstetrics and gynecology (OB/GYN) and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015–2017. Participants were assigned to 1 of 3 study arms: the LEADS (Leadership Education Advanced During Simulation) curriculum, a shortened TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized in order to limit any unintentional introduction of materials from the leadership curricula. The LEADS curriculum was developed in partnership with the Council on Resident Education in Obstetrics and Gynecology and Council of Residency Directors in Emergency Medicine as a novel way to provide a leadership toolkit. Both LEADS and the abbreviated TeamSTEPPS were designed as six 10-minute interactive web-based modules. The primary outcome of interest was the leadership performance score from the validated Clinical Teamwork Scale instrument measured during standardized high-fidelity simulation scenarios. Secondary outcomes were 9 key components of leadership from the detailed leadership evaluation measured on 5-point Likert scales. Both outcomes were rated by a blinded clinical video reviewer. Results: One hundred and ten OB/GYN and EM residents participated in this 2-year trial. Participants in both LEADS and TeamSTEPPS had statistically significant improvement in leadership scores from “average” to “good” ranges both immediately and at the 6-month follow-up, while controls remained unchanged in the “average” category throughout the study. There were no differences between the LEADS and TeamSTEPPS curricula with respect to the primary outcome. Conclusions: Residents who participated in a brief structured leadership training intervention had improved leadership skills that were maintained at 6-month follow-up

The current global situation for tuberculous meningitis : epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved]

CITATION: Seddon, J., et al. 2019. The current global situation for tuberculous meningitis : epidemiology, diagnostics, treatment and outcomes [version 1; peer review: 2 approved]. Wellcome Open Research, 4:167, doi:10.12688/wellcomeopenres.15535.1.The original publication is available at https://wellcomeopenresearch.orgTuberculous meningitis (TBM) results from dissemination of M. tuberculosis to the cerebrospinal fluid (CSF) and meninges. Ischaemia, hydrocephalus and raised intracranial pressure frequently result, leading to extensive brain injury and neurodisability. The global burden of TBM is unclear and it is likely that many cases are undiagnosed, with many treated cases unreported. Untreated, TBM is uniformly fatal, and even if treated, mortality and morbidity are high. Young age and human immunodeficiency virus (HIV) infection are potent risk factors for TBM, while Bacillus Calmette–Guérin (BCG) vaccination is protective, particularly in young children. Diagnosis of TBM usually relies on characteristic clinical symptoms and signs, together with consistent neuroimaging and CSF parameters. The ability to confirm the TBM diagnosis via CSF isolation of M. tuberculosis depends on the type of diagnostic tests available. In most cases, the diagnosis remains unconfirmed. GeneXpert MTB/RIF and the next generation Xpert Ultra offer improved sensitivity and rapid turnaround times, and while roll-out has scaled up, availability remains limited. Many locations rely only on acid fast bacilli smear, which is insensitive. Treatment regimens for TBM are based on evidence for pulmonary tuberculosis treatment, with little consideration to CSF penetration or mode of drug action required. The World Health Organization recommends a 12-month treatment course, although data on which to base this duration is lacking. New treatment regimens and drug dosages are under evaluation, with much higher dosages of rifampicin and the inclusion of fluoroquinolones and linezolid identified as promising innovations. The inclusion of corticosteroids at the start of treatment has been demonstrated to reduce mortality in HIV-negative individuals but whether they are universally beneficial is unclear. Other host-directed therapies show promise but evidence for widespread use is lacking. Finally, the management of TBM within health systems is sub-optimal, with drop-offs at every stage in the care cascade.https://wellcomeopenresearch.org/articles/4-167Publisher's versio

Management of histoplasmosis by infectious disease physicians

BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines for the management of histoplasmosis were last revised 15 years ago. Since those guidelines were compiled, new antifungal treatment options have been developed. Furthermore, the ongoing development of immunomodulatory therapies has increased the population at increased risk to develop histoplasmosis. METHODS: An electronic survey about the management practices of histoplasmosis was distributed to the adult infectious disease (ID) physician members of the IDSA\u27s Emerging Infections Network. RESULTS: The survey response rate was 37% (551/1477). Only 46% (253/551) of respondents reported seeing patients with histoplasmosis. Regions considered endemic had 82% (158/193) of physicians report seeing patients with histoplasmosis compared to 27% (95/358) of physicians in regions not classically considered endemic ( CONCLUSIONS: Though there are increased reports of histoplasmosis diagnoses outside regions classically considered endemic, a majority of ID physicians reported not seeing patients with histoplasmosis. Most respondents reported adherence to IDSA guidelines recommending itraconazole in each clinical situation. New histoplasmosis guidelines need to reflect the growing need for updated general guidance, particularly for immunocompromised populations

Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease.

Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations

Evidence in support of the call to ban the tackle and harmful contact in school rugby: a response to World Rugby

In a paper published in BJSM (June 2016), World Rugby employees Ross Tucker and Martin Raftery and a third coauthor Evert Verhagen took issue with the recent call to ban tackling in school rugby in the UK and Ireland. That call (to ban tackling) was supported by a systematic review published in BJSM. Tucker et al claim that: (1) the mechanisms and risk factors for injury along with the incidence and severity of injury in youth rugby union have not been thoroughly identified or understood; (2) rugby players are at no greater risk of injury than other sports people, (3) this is particularly the case for children under 15 years and (4) removing the opportunity to learn the tackle from school pupils might increase rates of injuries. They conclude that a ban ‘may be unnecessary and may also lead to unintended consequences such as an increase in the risk of injury later in participation.’ Here we aim to rebut the case by Tucker et al. We share new research that extends the findings of our original systematic review and meta-analysis. A cautionary approach requires the removal of the tackle from school rugby as the quickest and most effective method of reducing high injury rates in youth rugby, a public health priority

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.

BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation

Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study.

INTRODUCTION: Tuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. METHODS: In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. FINDINGS: From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. INTERPRETATION: Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. FUNDING: Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases

Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence of disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults. METHODS: We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018-2020. Participants underwent standardized urine-based TB screening. Urine (60 mcL) was tested with TB-LAM (Alere), and remaining urine was centrifuged with the cell pellet resuspended in 2 mL of urine for Xpert Ultra testing. RESULTS: We enrolled 348 HIV-positive inpatients with median CD4 of 37 cells/mcL (interquartile range, 13-102 cells/mcL). Overall, 26% (90 of 348; 95% confidence interval [CI], 21%-30%) had evidence of disseminated TB by either urine assay. Of 243 participants with both urine TB-LAM and Ultra results, 20% (48 of 243) were TB-LAM-positive, 12% (29 of 243) were Ultra-positive, and 6% (14 of 243) were positive by both assays. In definite and probable TB meningitis, 37% (14 of 38) were TB-LAM-positive and 41% (15 of 37) were Ultra-positive. In cryptococcal meningitis, 22% (40 of 183) were TB-LAM-positive and 4.4% (6 of 135) were Ultra-positive. Mortality trended higher in those with evidence of disseminated TB by either assay (odds ratio = 1.44; 95% CI, 0.83-2.49; P = .19) and was 6-fold higher in those with definite TB meningitis who were urine Ultra-positive (odds ratio = 5.67; 95% CI, 1.13-28.5; P = .04). CONCLUSIONS: In hospitalized Ugandans with advanced HIV disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%). In those with TB meningitis, urine tests were positive in over one third. There was little concordance between Ultra and TB-LAM, which warrants further investigation

Combined Mesenchymal Stromal Cell Therapy and ECMO in ARDS:A Controlled Experimental Study in Sheep

Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO. Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO. Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell-derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low VT ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring. Measurements and Main Results: The administration of hMSCs did not improve oxygenation (PaO2/FIO2 mean difference =2146mmHg; P= 0.076) or pulmonary function.However, histological evidence of lung injury(lung injuryscoremeandifference=20.07;P=0.04) and BALIL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. Thiswas accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers. Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO. </p