Structure of the five-coordinate CoII complex (1H-imidazole){tris-[(1-benzyl-triazol-4-yl-κN3)meth-yl]amine-κN}cobalt(II) bis-(tetra-fluoro-borate).

The title compound, [Co(C3H4N2)(C30H30N10)](BF4)2, is a five-coordinate CoII complex based on the neutral ligands tris-[(1-benzyl-triazol-4-yl)meth-yl]amine (tbta) and imidazole. It exhibits a distorted trigonal bipyramidal geometry in which the equatorial positions are occupied by the three N-atom donors from the triazole rings of the tripodal tbta ligand. The apical amine N-atom donor of tbta and the N-atom donor of the imidazole ligand occupy the axial positions of the coordination sphere. Two tetra-fluoro-borate anions provide charge balance in the crystal.

Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

OBJECTIVES: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary care hospital and 15 community and academic centers of a large healthcare system. PATIENTS: Hospitalized patients with PE treated with systemic alteplase. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. CONCLUSIONS: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

Association of Internal Medicine Point of Care Ultrasound (POCUS) with Length of Stay, Hospitalization Costs, and Formal Imaging: a Prospective Cohort Study.

Background: Point of care ultrasound (POCUS) use has rapidly expanded among internal medicine (IM) physicians in practice and residency training programs. Many benefits have been established; however, studies demonstrating the impact of POCUS on system metrics are few and mostly limited to the emergency department or intensive care setting. The study objective was to evaluate the impact of inpatient POCUS on patient outcomes and hospitalization metrics. Methods: Prospective cohort study of 12,399 consecutive adult admissions to 22 IM teaching attendings, at a quaternary care teaching hospital (7/1/2011-6/30/2015), with or without POCUS available during a given hospitalization. Multivariable regression and propensity score matching (PSM) analyses compared multiple hospital metric outcomes (costs, length of stay, radiology-based imaging, satisfaction, etc.) between the "POCUS available" vs. "POCUS unavailable" groups as well as the "POCUS available" subgroups of "POCUS used" vs. "POCUS not used". Results: Patients in the "POCUS available" vs. "POCUS unavailable" group had lower mean total and per-day hospital costs ($17,474 vs. $21,803, p<0.001; $2,805.88 vs. $3,557.53, p<0.001), lower total and per-day radiology cost ($705.41 vs. $829.12, p<0.001; $163.11 vs. $198.53, p<0.001), fewer total chest X-rays (1.31 vs. 1.55, p=0.01), but more chest CTs (0.22 vs 0.15; p=0.001). Mean length of stay (LOS) was 5.77 days (95% CI = 5.63, 5.91) in the "POCUS available" group vs. 6.08 95% CI (5.66, 6.51) in the "POCUS unavailable" group (p=0.14). Within the "POCUS available" group, cost analysis with a 4:1 PSM (including LOS as a covariate) compared patients receiving POCUS vs. those that could have but did not, and also showed total and per-day cost savings in the "POCUS used" subgroup ($15,082 vs. 15,746; p<0.001 and $2,685 vs. $2,753; p=0.04). Conclusions: Availability and selected use of POCUS was associated with a meaningful reduction in total hospitalization cost, radiology cost, and chest X-rays for hospitalized patients.

Field- and Temperature-Dependent Paramagnetic Relaxation Enhancements in Co(II) Trispyrazolylmethanes.

A comprehensive field- and temperature-dependent examination of nuclear magnetic resonance paramagnetic relaxation enhancements (PREs) for the constitutive protons of [Co(Tpm)2][BF4]2 is presented. Data for an apically substituted derivative clearly establish that bis-Tpm complexes of Co(II) undergo Jahn-Teller dynamics about the molecular threefold axis. PREs from the parent Tpm complex were used to numerically extract the electron relaxation times (T1e). The Tpm complex showed field-dependent behavior, with an approximately 40% higher activation barrier than the related trispyrazolylborate (Tp) complex, based on fits to the T1e vs T, B0 data. Analysis of the field-dependent line widths revealed a surprisingly large contribution from susceptibility (Curie) relaxation (20-35% at the highest field), and a molecular radius (9.5 Å) that is consistent with a tightly associated counterion slowing rotation in solution. Density functional theory showed a shared vibration that is consistent with the Jahn-Teller and appears proportionately higher in energy in [Co(Tpm)2]2+. Complete active-space self-consistent field calculations support ascribing electron relaxation to enhanced mixing of the two Eg orbital sets that accompanies the tetragonal distortion and the differences in electron correlation times to the higher Jahn-Teller activation barrier in [Co(Tpm)2]2+.

Outcomes and Clinical Characteristics of COVID-19 in Patients with Tuberculosis: A Retrospective Matched Cohort Study.

The outcomes and characteristics of acute coronavirus disease 2019 (COVID-19) infection in patients with tuberculosis (TB) represent an evolving area of literature. This retrospective cohort study (March 2020-January 2021) within a large United States health system evaluated clinical and demographic characteristics, illness severity, complications, and mortality associated with acute COVID-19 infection in patients with TB (n = 31) compared to a matched (1:3) COVID-19 cohort without TB (n = 93). In the COVID-19 + TB cohort, TB was active in 32% and latent in 65% of patients, most patients (55%) had pulmonary TB, and 68% had previously undergone treatment for their TB. Patients with COVID-19 + TB infection had higher rates of hospitalization (45% vs. 36%, p = 0.34), intensive care unit (ICU) stay (16% vs. 8%, p = 0.16), and need for mechanical ventilation (13% vs. 3% p = 0.06). Discordant with those higher rates of markers typically denoting more severe illness, TB patients with acute COVID-19 did not have longer length-of-stay (5.0 vs. 6.1 days, p = 0.97), in-hospital mortality (3.2% vs. 3.2%, p = 1.00), or 30-day mortality (6.5% vs. 4.3%, p = 0.63). This study, while having limitations for extrapolation, cautions the notion that patients with COVID-19 and TB infers worse outcomes and adds to the growing body of literature on the interaction between these two infections.

Retrospective Analysis of Direct-Acting Oral Anticoagulants (DOACs) Initiation Timing and Outcomes After Thrombolysis in High- and Intermediate-Risk Pulmonary Embolism.

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P < .0001). This single institution retrospective study suggests DOAC initiation <48 h from thrombolysis may result in shorter hospital LOS compared to DOAC initiation ≥48 h (P < .0001). Further larger studies with more robust research methodology are needed to address this important clinical question.

Beyond the individual: Sexual minority help-seeking and the consequences of structural barriers.

Sexual minorities report more psychological distress, unmet mental health needs, and barriers to mental health care compared with heterosexuals, yet little is known about their barriers to seeking out mental health care. The present study reports the factors that influence intentions to seek out mental health care of a national survey of 398 sexual minorities. Structural equation modeling identified structural barriers, such as cost, time, and knowing how to access services, as the strongest predictor of sexual minorities' help-seeking intentions. Latent moderators indicated sexual minorities' help-seeking intentions varied depending upon their degree of psychological distress. This revealed a pattern where the most vulnerable participants (i.e., those with high structural barriers and negative help-seeking attitudes) were willing to pursue mental health care only when they were experiencing significant distress. Furthermore, nearly 40% of participants reported unmet mental health needs, and structural barriers were the primary reasons for this deficit. Findings from this study contrast with previous mental health help-seeking research by emphasizing the importance of structural vulnerability, which refers to the external forces that frame and constrain choices, thereby impeding decision-making and limiting life options for those who are in systemically disadvantaged social positions. These findings are discussed in terms of counseling psychology training, practice, social justice advocacy, and future health care research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

International consensus conference recommendations on ultrasound education for undergraduate medical students.

OBJECTIVES: The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. METHODS: 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. RESULTS: A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. CONCLUSIONS: The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

Applying the DSM-5 Alternative Model of Personality Disorders and the Shedler-Westen Assessment Procedure to the Classic Case of "Madeline G.": Novice and Expert Rater Convergences and Divergence.

Prior research supports the learnability of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Alternative Model of Personality Disorders (AMPD). However, researchers have yet to compare novice ratings on the AMPD's Level of Personality Functioning Scale and the 25 pathological personality traits with expert ratings. Furthermore, the AMPD has yet to be examined with the idiographic Shedler-Westen Assessment Procedure (SWAP). We compared the aggregated AMPD clinical profile of a group of psychology doctoral students who learned the AMPD to high levels of reliability to that of an expert rater using the crucible of the classical case of "Madeline G." Examination of AMPD and SWAP ratings of "Madeline G." revealed excellent overall concordance but suggests that novice raters tend to perceive lower levels of personality impairment.

Post-thrombolytic coagulopathy and complications in patients with pulmonary embolism treated with fixed-dose systemic alteplase.

BACKGROUND: Alteplase treatment can cause a systemic coagulopathy although the incidence and contributory factors are unknown in pulmonary embolism (PE). Fixed-dosing of alteplase for PE may lead to interpatient variability in drug exposure and influence post-thrombolytic coagulopathy (PTC). While changes in fibrinogen and INR have been used to describe PTC, no universal PTC definition is available. OBJECTIVES: Evaluate the incidence of PTC after alteplase treatment for PE, the effect of patient weight and blood/plasma volume and the association with bleeding complications. METHODS: We conducted a retrospective cohort study of patients treated with alteplase for massive or high-risk submassive PE. Demographics, alteplase dosing, laboratory assessment of coagulopathy, and bleeding events were collected. The primary endpoint was incidence of PTC defined as an international normalized ratio (INR) > 1.5 or fibrinogen < 170 mg/dL. Secondary outcomes included correlation between coagulopathies and alteplase dose normalized to actual body weight (ABW), ideal body weight (IBW), plasma volume (PV), and estimated blood volume (EBV). Bleeding events in patients with and without PTC were compared. RESULTS: 125 patients met criteria for inclusion in the study. PTC occurred in 35.3% of patients, with INR >1.5 in 21.8% and fibrinogen <170 mg/dL in 26%. Alteplase dose >50 mg was associated with increased odds of PTC (OR 6.5, CI 2.1-19.9). Dose normalized to ABW and EBV correlated weakly with absolute increase in post-alteplase INR (r =0.20, p =0.06 and r =0.21, p =0.057 respectively) and to percent change in INR (r =0.20, p = 0.058 and r =0.21, p =0.048 respectively). Dose/ABW, dose/PV, and dose/EBV each correlated moderately with absolute decrease in fibrinogen (r =-0.53, -0.49, and -0.47 respectively, p <0.001 for each) and percent change in fibrinogen (r = -0.55, -0.49, and -0.49 respectively, p < 0.001 for each). Dose/IBW correlated weakly with absolute and percent decrease in fibrinogen (r = -0.32, p =0.013 and r =-0.33, p =0.011). Patients with bleeding were more likely to have PTC (58.3% vs. 28.6%, p= 0.05) and a bleeding event was predictive of PTC (OR 5.33, 1.32-23.99). CONCLUSIONS: PTC is prevalent in patients with PE. PTC is influenced by alteplase dose and exposure parameters (ABW, IBW, PV, EBV) and may contribute to the bleeding risk.

An Ultrasound Screening Exam During Medicare Wellness Visits May Be Beneficial.

OBJECTIVES: The physical exam component of a periodic health visit in the elderly has not been considered useful. Standard Medicare Wellness visits require no physical exam beyond blood pressure and most physicians perform limited exams during these visits. The objective of this study was to test the feasibility, potential benefit, and costs of performing a screening ultrasound (US) exam during Medicare Wellness visits. METHODS: A physician examiner at an academic internal medicine primary care clinic performed a screening US exam targeting important abnormalities of patients 65-85 years old during a Medicare Wellness visit. The primary care physician (PCP) recorded the follow-up items for each abnormality identified by the US examiner and assessed the benefit of each abnormality for the participant. Abnormality benefit, net exam benefit per participant, follow-up items and costs, participant survey results, and exam duration were assessed. RESULTS: Participants numbered 108. Total abnormalities numbered 283 and new diagnoses were 172. Positive benefit scores were assigned to 38.8%, neutral (zero) scores to 59.4%, and negative benefit scores to 1.8% of abnormalities. Net benefit scores per participant were positive in 63.9%, 0 in 34.3%, and negative in 1.8%. Follow-up items were infrequent resulting in 76% of participants without follow-up cost. Participant survey showed excellent acceptance of the exam. CONCLUSIONS: The US screening exam identified frequent abnormalities in Medicare Wellness patients. The assessed benefits were rarely negative and often mild to moderately positive, with important new chronic conditions identified. Follow-up costs were low when the PCPs were also US experts.

Integration of Point-of-Care Ultrasound Education Into the Internal Medicine Core Clerkship Experience.

Point-of-care ultrasound (POCUS) is becoming an essential skill for internists. To date, there are no professional guidelines for how POCUS skills should be taught to medical students. A panel of POCUS experts from seven academic medical centers in the United States was convened to describe the components of independently developed IM clerkship POCUS training programs, identify areas of similarity and difference, and propose recommendations for alignment.

Fluorine Labeling of ortho-Phenylenes to Facilitate Conformational Analysis.

1H NMR spectroscopy is a powerful tool for the conformational analysis of ortho-phenylene foldamers in solution. However, as o-phenylenes are integrated into ever more complex systems, we are reaching the limits of what can be analyzed by 1H- and 13C-based NMR techniques. Here, we explore fluorine labeling of o-phenylene oligomers for analysis by 19F NMR spectroscopy. Two series of fluorinated oligomers have been synthesized. Optimization of monomers for Suzuki coupling enables an efficient stepwise oligomer synthesis. The oligomers all adopt well-folded geometries in solution, as determined by 1H NMR spectroscopy and X-ray crystallography. 19F NMR experiments complement these methods well. The resolved singlets of one-dimensional 19F{1H} spectra are very useful for determining relative conformer populations. The additional information from two-dimensional 19F NMR spectra is also clearly valuable when making 1H assignments. The comparison of 19F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o-phenylene geometries.

Adult Shigatoxin-mediated hemolytic uremic syndrome masked by alcohol use and inflammatory bowel disease.

Diagnosing uncommon diseases in individuals with underlying medical conditions can be challenging. Cognitive bias can lead to delayed or missed disease management. We present a case of Shiga-toxin mediated hemolytic uremic syndrome (ST-HUS) in a 46-year-old man with ulcerative colitis and alcohol use disorder who presented with acute alcohol intoxication, non-bloody diarrhoea and coffee ground emesis. He was admitted to the hospital for alcoholic ketoacidosis, alcohol withdrawal and possible upper gastrointestinal bleed, but ultimately, he developed severe thrombocytopaenia, hemolytic anaemia, acute renal failure and prolonged altered mentation. Given that ST-HUS is uncommon in adults, his initial report of diarrhoea was attributed to alcohol use or underlying active ulcerative colitis and not connected to his haematologic abnormalities. He was initially started on plasmapheresis; however, thrombotic microangiopathy work up revealed Shiga-toxin in his stool and ADAMST13 levels within normal limits. Subsequently, he was transitioned to supportive care for management of ST-HUS.

Mycotic aortic aneurysm due to Capnocytophaga species infection treated non-surgically.

Capnocytophaga canimorsus, a commensal organism in canine flora, is most frequently transmitted to humans via animal bite. Infection can lead to multiorgan failure, disseminated intravascular coagulation, and uncommonly mycotic aneurysm. We present a case of a 65-year-old male who presented to the emergency department with right lower quadrant abdominal pain, nausea with vomiting, and diarrhea that began the evening prior to presentation. A computed tomography (CT) scan of the abdomen and pelvis with contrast demonstrated a 4.3 cm fusiform infrarenal aortic aneurysm concerning for a mycotic aneurysm. Vascular surgery felt there was a low likelihood of rupture and empiric antimicrobials were started. Eventually blood cultures grew a Capnocytophaga species and antimicrobials were then narrowed to imipenem. No surgical intervention was performed. Serial imaging showed stability of aneurysm with improvement and later complete resolution of inflammatory changes one month after onset of symptoms. This is the first reported case of Capnocytophaga mycotic aneurysm that was treated with antimicrobials alone and no surgical intervention.

Hospitalist Perceptions of Barriers to Lung Ultrasound Adoption in Diverse Hospital Environments.

Despite the many advantages of lung ultrasound (LUS) in the diagnosis and management of patients with dyspnea, its adoption among hospitalists has been slow. We performed semi-structured interviews of hospitals from four diverse health systems in the United States to understand determinants of adoption within a range of clinical settings. We used the diffusion of innovation theory to guide a framework analysis of the data. Of the 27 hospitalists invited, we performed 22 interviews from four hospitals of diverse types. Median years post-residency of interviewees was 10.5 [IQR:5-15]. Four main themes emerged: (1) There are important clinical advantages to LUS despite operator dependence, (2) LUS enhances patient and clinician experience, (3) Investment of clinician time to learn and perform LUS is a barrier to adoption but yields improved efficiency for the health system and (4) Mandated training and use may be necessary to achieve broad adoption as monetary incentives are less effective. Despite the perceived benefits of LUS for patients, clinicians and health systems, a significant barrier to broad LUS adoption is the experience of time scarcity by hospitalists. Future implementation strategies should focus on changes to the clinical environment that address clinician barriers to learning and adoption of new skills.

Spectroscopic and biochemical characterization of metallo-ß-lactamase IMP-1 with dicarboxylic, sulfonyl, and thiol inhibitors.

In an effort to probe the biophysical mechanisms of inhibition for ten previously-reported inhibitors of metallo-ß-lactamases (MBL) with MBL IMP-1, equilibrium dialysis, metal analyses coupled with atomic absorption spectroscopy (AAS), native state mass spectrometry (native MS), and ultraviolet-visible spectrophotometry (UV-VIS) were used. 6-(1H-tetrazol-5-yl) picolinic acid (1T5PA), ANT431, D/l-captopril, thiorphan, and tiopronin were shown to form IMP-1/Zn(II)/inhibitor ternary complexes, while dipicolinic acid (DPA) and 4-(3-aminophenyl)pyridine-2,6-dicarboxylic acid (3AP-DPA) stripped some metal from the active site of IMP but also formed ternary complexes. DPA and 3AP-DPA stripped less metal from IMP-1 than from VIM-2 but stripped more metal from IMP-1 than from NDM-1. In contrast to a previous report, pterostilbene does not appear to bind to IMP-1 under our conditions. These results, along with previous studies, demonstrate similar mechanisms of inhibition toward different MBLs for different MBL inhibitors.

Sexual Orientation Beliefs and Identity Development: A Person-Centered Analysis among Sexual Minorities.

We conducted person-centered analysis of sexual orientation beliefs among sexual minorities to explore potential relationships between these beliefs and sexual orientation, developmental milestones, race and ethnicity, and attitudes about sexual orientation. We recruited participants (N = 416) via Amazon Mechanical Turk who completed measures of beliefs about sexual orientation and attitudes about their own sexuality, as well as assessments of mental health and age of sexual identity development milestones. We conducted a latent profile analysis and found three distinct sexual orientation belief profiles, similar to those previously observed in predominantly straight samples. We found that sexual orientation and race-ethnicity predicted belief profile membership, with the latter exhibiting the most substantial effect. Of the four identity developmental milestones tested, only the age of first same-sex attraction predicted belief profile membership. Across profiles, members differed significantly in their mean endorsement of both positive and negative attitudes regarding sexual orientation and psychological distress. Thus, the current research suggests that sexual orientation beliefs are powerful constructs in the lives of sexual minorities, with relationships to sexual orientation, other social identities, and mental health.

Tris-(2-pyridylmethyl)amine-ligated Cu(II) 1,3-diketonate complexes: anaerobic retro-Claisen and dehalogenation reactivity of 2-chloro-1,3-diketonate derivatives.

We report synthetic, structural and reactivity investigations of tris-(2-pyridylmethyl)amine (TPA)-ligated Cu(ii) 1,3-diketonate complexes. These complexes exhibit anaerobic retro-Claisen type C-C bond cleavage reactivity which exceeds that found in analogs supported by chelate ligands with fewer and/or weaker pyridyl interactions.