Abstract
Helioseismic data for solar cycles 23 and 24 have shown unequivocally that solar dynamics changes with solar activity. Changes in solar structure have been more difficult to detect. Basu & ...Mandel had claimed that the then-available data revealed changes in the He
ii
ionization zone of the Sun. The amount of change, however, indicated the need for larger than expected changes in the magnetic fields. Now that helioseismic data spanning two solar cycles are available, we have redone the analysis using improved fitting techniques. We find that there is indeed a change in the region around the He
ii
ionization zone that is correlated with activity. Because the data sets now cover two solar cycles, the time variation is easily discernible.
Abstract
We present Chandra X-ray observations of the dynamically complex galaxy cluster A119 (
z
= 0.044). A119 is host to two narrow-angle-tail (NAT) radio sources (0053-015 and 0053-016), whose ...tails are oriented parallel to each other, despite orthogonally oriented jet axes. Imaging and spectral analysis reveal X-ray emission elongated along the NE–SW axis, along with the presence of complex structures, including surface brightness discontinuities, which suggest possible merger activity along this axis. From radial profiles of the X-ray surface brightness, temperature, pressure, and density, we identify two surface brightness edges that are found to be cold fronts, possibly associated with large-scale sloshing of intracluster medium gas. We also identify a brightness edge to the S that is found to be a shock front with Mach number
M
= 1.21 ± 0.11, consistent with a merger shock. In addition, previous optical studies show the alignment of optical substructures along the N–S direction. The elongated X-ray emission, orientations of the NAT tails, and alignment of the optical substructure all suggest recent or ongoing merger activity in the NE–SW direction.
Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and ...behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded.
To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care.
Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009.
After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI.
Acute myocardial infarction.
We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66).
Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.
To assess the effect of an antimicrobial stewardship program (ASP)–bundled initiative on the appropriate use of antibiotics for uncomplicated skin and soft tissue infections (uSSTIs) at 2 academic ...medical centers in Pittsburgh, Pennsylvania.
A retrospective preintervention and postintervention study was conducted to compare management of patients admitted with uSSTIs before and after the implementation of the bundled initiative. The preintervention period was from August 1, 2014, through March 31, 2015, and the postintervention period was from August 1, 2015, through March 31, 2016.
A total of 160 patients were included in the preintervention cohort, and 163 were included in the postintervention cohort. Compared with the preintervention group, the mean duration of therapy decreased (12.5 days vs 8.8 days; P<.001) and an appropriate duration of less than 10 days increased in more patients (20.6% 33 of 160 vs 68.7% 112 of 163; P<.001) in the postintervention period. Fewer patients were exposed to antimicrobials with extended gram-negative (44.4% 71 of 160 vs 9.2% 15 of 163; P<.001), anaerobic (39.4% 63 of 160 vs 9.8% 16 of 163; P<.001), and antipseudomonal (16.3% 26 of 160 vs 1.8% 3 of 163; P<.001) coverage. The mean length of stay decreased from 3.6 to 2.2 days (P<.001) without an increase in 30-day readmissions (6.3% 10 of 160 vs 4.9% 8 of 163; P=.64). The ASP made recommendations for 125 patients, and 96% were accepted.
Implementation of an ASP-bundled approach aimed at optimizing antibiotic therapy in the management of uSSTIs led to shorter durations of narrow-spectrum therapy as well as shorter hospital length of stay without adversely affecting hospital readmissions.
Cisgenderism is the ideology that delegitimizes people's own designations of their genders and bodies. Family therapy (FT) offers a systemic, non-pathologizing framework for working with people who ...have experienced cisgenderism. Unfortunately, FT practices, like those of many mental health professionals, are often cisgenderist. The authors discuss literature on cisgenderism, explore implications of therapists' and supervisors' cisgenderist practices, and provide a brief self-reflection tool.
Abstract
Background
Patients admitted with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often are prescribed antibiotics. Studies have shown that the use of procalcitonin ...(PCT) to guide the decision to initiate antibiotic therapy in AECOPD has resulted in less antibiotic use and similar outcomes compared with standard of care. We evaluated patients with AECOPD and low PCT concentrations to determine whether antibiotic therapy was associated with improved outcomes.
Methods
We retrospectively evaluated adult patients admitted with AECOPD who had a peak PCT concentration <0.25 µg/mL. Patients were evaluated based on their antibiotic exposure: ≤24 hours vs >24 hours. We also evaluated outcomes based upon the duration of azithromycin therapy: ≤24 hours vs >24 hours. The primary outcome was all-cause 30-day readmissions. Secondary outcomes included length of stay (LOS) and COPD-related 30-day readmissions.
Results
One hundred sixty-one and 195 patients received ≤24 hours vs >24 hours of antibiotic therapy, respectively. The cohort with ≤24 hours of antibiotics had a shorter LOS (2.8 vs 3.7 days; P = .01). There were no differences in all-cause 30-day readmissions (15.5% vs 17.4%; P = .63) or COPD-related 30-day readmissions (11.2% vs 12.3%; P = .74). Additionally, patients receiving ≤24 hours of azithromycin had a shorter LOS (3.0 vs 3.8 days; P = .002) and there were no differences in all-cause 30-day readmissions (16.2% vs 17.1%; P = .82) or COPD-related 30-day readmissions (11.9% vs 11.6%; P = .94).
Conclusions
For adult patients hospitalized with nonsevere AECOPD and low PCT concentrations, antibiotic therapy beyond 24 hours did not improve outcomes.
Patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease with a low procalcitonin concentration do not benefit from antibiotic therapy in regard to hospital length of stay or readmission rates.
Despite three decades of dramatic treatment breakthroughs in antiretroviral regimens, clinical outcomes for people living with HIV vary greatly. The HIV treatment cascade models the stages of care ...that people living with HIV go through toward the goal of viral suppression and demonstrates that <30% of those living with HIV/AIDS in the United States have met this goal. Although some research has focused on the ways that patient characteristics and patient-provider relationships contribute to clinical adherence and treatment success, few studies to date have examined the ways that contextual factors of care and the healthcare environment contribute to patient outcomes. Here, we present qualitative findings from a mixed-methods study to describe contextual and healthcare environment factors in a Ryan White Part C clinic that are associated with patients' abilities to achieve viral suppression. We propose a modification of Andersen's Behavioral Model of Health Services Utilization, and its more recent adaptation developed by Ulett et al., to describe the ways that clinic, system, and provider factors merge to create a system of care in which more than 86% of the patient population is virally suppressed.
Community-acquired pneumonia and healthcare-associated pneumonia are often treated with prolonged antibiotic therapy. Procalcitonin (PCT) has effectively and safely reduced antibiotic use for ...pneumonia in controlled studies. However, limited data exist regarding PCT guidance in real-world settings for management of pneumonia.
A retrospective, preintervention/postintervention study was conducted to compare management for patients admitted with pneumonia before and after implementation of PCT guidance at 2 teaching hospitals in Pittsburgh, Pennsylvania. The preintervention period was March 1, 2014 through October 31, 2014, and the postintervention period was March, 1 2015 through October 31, 2015.
A total of 152 and 232 patients were included in the preintervention and postintervention cohorts, respectively. When compared with the preintervention group, mean duration of therapy decreased (9.9 vs 6.0 days; P < .001). More patients received an appropriate duration of 7 days or less (26.9% vs 66.4%; P < .001). Additionally, mean hospital length of stay decreased in the postintervention group (4.9 vs 3.5 days; P = .006). Pneumonia-related 30-day readmission rates (7.2% vs 4.3%; P = .26) were unaffected. In the postintervention group, patients with PCT levels <0.25 µg/L received shorter mean duration of therapy compared with patients with levels >0.25 µg/L (4.6 vs 8.0 days; P < .001), as well as reduced hospital length of stay (3.2 vs 3.9 days; P = .02).
In this real-world study, PCT guidance led to shorter durations of total antibiotic therapy and abridged inpatient length of stay without affecting hospital readmissions.
Background: Isocitrate dehydrogenase 1 mutations (IDH1m) occur in 7-14% of AML patients and 3% of MDS patients and produce 2-hydroxyglutarate (2-HG), an oncometabolite that impairs differentiation. ...FT-2102 is an oral, highly potent, selective small molecule inhibitor of mutated IDH1, with the therapeutic potential to restore normal cellular differentiation. Herein, we present preclinical and clinical data from an ongoing Phase 1/2 study of single-agent (SA) FT-2102 in patients with IDH1m AML and MDS (CT.gov: NCT02719574).
Methods: Extensive pre-clinical evaluations were performed on FT-2102, including CYP interactions in-vivo in rat and in-vitro in human tissue and in-vivo QTc toxicology in monkeys. The clinical Phase 1 study was initiated to evaluate the safety, PK/PD, and antileukemic activity of FT-2102 in patients with IDH1m AML or MDS and included both dose escalation and expansion phases. FT-2102 was administered daily until disease progression or unacceptable toxicity. Eligibility criteria included: IDH1m AML/MDS relapsed/refractory (R/R) or treatment naïve (TN) for whom standard therapy was contraindicated, adequate liver and renal function, no prior IDH1 inhibitors, and no restrictions for concomitant non-anticancer medications. Investigator-assessed responses were per modified IWG 2003/2006 criteria. Efficacy was assessed at Cycle 2 Day 1 and as clinically indicated thereafter. Adverse events (AEs) were assessed throughout the study per NCI CTCAE version 4.03.
Results: Evaluation of FT-2102 in in-vivo rat and in-vitro human tissue indicated hepatic metabolism by CYP enzymes (CPY3A4, 2C9, 1A1) as the major route of excretion. Animal toxicology studies predicted the threshold for QTc risk occurred at exposures >5.5 fold higher than the murine exposure at which 90% 2-HG reduction was observed.
In the clinical study, at the time of the data cutoff, 31 patients (pts) had been treated with SA FT-2102, with a median of 3 mo. on treatment (range: 0.2 to 20 mo.). Of the 31pts treated, 25 had AML (22 R/R; 3 TN) and 6 had MDS (4 R/R; 2 TN). The median number of prior anti-leukemia therapies was 2 (range: 0-9) for AML pts and 1 (range: 0-4) for MDS pts. FT-2102 doses were: 150 mg QD (n=8), 300 mg QD (n=4), 150 mg BID (n=16), and 100 mg QD with food (n=3). Eighteen pts discontinued treatment, most commonly due to death (n=5), progressive disease (n=5), HSCT (n=3), or lack of response (n=3).
Severe (≥Grade 3) AEs occurring in >5% of pts included thrombocytopenia (26%), febrile neutropenia (23%), anemia (19%), pneumonia (13%), neutropenia (7%), hypokalemia (7%), pyrexia (7%) and leukocytosis (6%). Three pts had differentiation syndrome (IDH-DS), which resolved with temporary interruption of FT-2102, treatment with dexamethasone, hydroxyurea, and supportive care in all three. One pt had transient QTcF prolongation (Grade 3) which resolved with temporary interruption of FT-2102 and cessation of suspected concomitant medications. Eight pts died on treatment or within 28 days of the last dose, with no deaths considered related to FT-2102. No DLTs were observed during dose escalation.
Selection of FT-2102 150 mg BID as the RP2D was supported by PK and PD data. Durable steady-state (Css) achieved by Week 2 was well below the threshold for QTc risk predicted by preclinical studies. The predicted IC90 was confirmed with prompt and durable 2-HG reduction to normal levels by C2D1 at the RP2D.
Table 1 shows the Investigator-assessed ORR per IWG. Responses have been observed from 1 to 6 months on treatment, with stable disease observed beyond 6 months; 42% of the patients remain on treatment.
Conclusions: FT-2102 preclinical evaluations suggest a low risk of clinically significant CYP-mediated drug-drug interaction and QTc prolongation. SA FT-2102 is well tolerated in AML and MDS, with 150 mg BID selected as the RP2D based on safety, PK and PD (2-HG) response. Significant clinical activity has been observed in heavily pre-treated and in TN patients, both in AML and MDS. FT-2102 continues being investigated at a dose of 150 mg BID in a Phase 2 study. Three SA Phase 2 cohorts are currently open for enrollment in R/R AML, AML/MDS with CR/CRi (i.e., with MRD), and in pts with R/R MDS/AML with prior exposure to an IDH1m inhibitor. Data updates will be available at the time of presentation.
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Lee:LAM Therapeutics: Research Funding; Karyopharm Therapeutics Inc: Consultancy; AstraZeneca: Consultancy; Clinipace: Consultancy; Amgen: Consultancy. Schiller:Celator/Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding. Ferrell:Incyte: Research Funding. Kelly:Forma Therapeutics Inc.: Employment. Li:Forma Therapeutics Inc.: Employment. Sweeney:Forma Therapeutics Inc.: Employment. Watson:Forma Therapeutics Inc.: Employment. Mohamed:Forma Therapeutics Inc.: Employment. Cortes:Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.
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