Synthesis and Structure–Activity Relationships of N-Benzyl Phenethylamines as 5-HT2A/2C Agonists

相似文献   

Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort

Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM_2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied.Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM_2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data.Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m³ for PM_2.5 and from 0.1 to 1.7 μg/m³ for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM_2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM.Conclusions: Greater exposure to PM_2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy.Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose tolerance during pregnancy: the Project Viva Cohort. Environ Health Perspect 122:378–383; http://dx.doi.org/10.1289/ehp.1307065     

An Intensive Intervention to Reduce Readmissions for Frequently Hospitalized Patients: the CHAMP Randomized Controlled Trial

BackgroundA small number of patients are disproportionally readmitted to hospitals. The Complex High Admission Management Program (CHAMP) was established as a multidisciplinary program to improve continuity of care and reduce readmissions for frequently hospitalized patients.ObjectiveTo compare hospital utilization metrics among patients enrolled in CHAMP and usual care.DesignPragmatic randomized controlled trial.ParticipantsInclusion criteria were as follows: 3 or more, 30-day inpatient readmissions in the previous year; or 2 inpatient readmissions plus either a referral or 3 observation admissions in previous 6 months.InterventionsPatients randomized to CHAMP were managed by an interdisciplinary team including social work, physicians, and pharmacists. The CHAMP team used comprehensive care planning and inpatient, outpatient, and community visits to address both medical and social needs. Control patients were randomized to usual care and contacted 18 months after initial identification if still eligible.Main MeasuresPrimary outcome was number of 30-day inpatient readmissions 180 days following enrollment. Secondary outcomes were number of hospital admissions, total hospital days, emergency department visits, and outpatient clinic visits 180 days after enrollment.Key ResultsThere were 75 patients enrolled in CHAMP, 76 in control. Groups were similar in demographic characteristics and baseline readmissions. At 180 days following enrollment, CHAMP patients had more inpatient 30-day readmissions [CHAMP incidence rate 1.3 (95% CI 0.9–1.8) vs. control 0.8 (95% CI 0.5–1.1), p=0.04], though both groups had fewer readmissions compared to 180 days prior to enrollment. We found no differences in secondary outcomes.ConclusionsFrequently hospitalized patients experienced reductions in utilization over time. Though most outcomes showed no difference, CHAMP was associated with higher readmissions compared to a control group, possibly due to consolidation of care at a single hospital. Future research should seek to identify subsets of patients with persistently high utilization for whom tailored interventions may be beneficial.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640KEY WORDS: care transitions, readmissions, care models, continuity of care, randomized controlled trial

A small number of patients account for a disproportionate number of hospital readmissions.¹ While medically diverse, many patients who are frequently hospitalized have behavioral or social needs that require holistic care models emphasizing more than medical care alone.² This population challenges a system of care that fragments hospital-based care and ambulatory care, creating systematic discontinuity for patients who may require longitudinal relationship-based care to meet their complex needs.³ In qualitative studies, patients who are frequently hospitalized report frustration with care fragmentation, causing them to perceive a lack of continuity and a loss of trust with the medical system.⁴Innovative care models have sought to reduce readmissions through redesigning care delivery, improving care coordination, and connecting patients to existing resources.^5–8 A systematic review of interventions for frequently hospitalized patients found a heterogeneous group of care models.⁹ Importantly, the majority of studies were observational. Many patients experience a reduction in utilization after an initial period of frequent admissions,¹⁰ limiting the ability of observational studies to measure a specific program’s effect due to the natural decline in readmissions over time. A randomized trial of a “healthcare hotspotting” intervention for patients in Camden, NJ, reported no change in hospitalization rates compared to a control group.¹¹ Though this intervention was an intensive interdisciplinary effort that enrolled patients while still hospitalized, it focused primarily on connecting patients to existing outpatient resources. Other intensive outpatient-only interventions have failed to reduce healthcare utilization.¹² Interventions that focus on improving care across clinical settings (i.e., both inside and outside of the hospital) may have a different effect.We created the Complex High Admission Management Program (CHAMP) as a quality improvement initiative to improve inpatient and outpatient care and reduce inpatient readmissions of patients frequently admitted to our hospital. The CHAMP multidisciplinary team works to foster longitudinal relationships with patients who suffer from systematic discontinuity. A pilot pre-post analysis of CHAMP observed reductions in readmission;¹³ however, results may have been confounded by the aforementioned tendency for utilization to decline over time.¹⁰ In this study, we conducted a randomized trial of CHAMP compared with usual care to accurately assess the program’s effect on hospital readmissions.     

Psychosocial care for children receiving chimeric antigen receptor (CAR) T‐cell therapy

Chimeric antigen receptor (CAR) T‐cell therapy has transformed the treatment of relapsed/refractory B‐cell acute lymphoblastic leukemia (ALL). However, this new paradigm has introduced unique considerations specific to the patients receiving CAR T‐cell therapy, including prognostic uncertainty, symptom management, and psychosocial support. With increasing availability, there is a growing need for evidence‐based recommendations that address the specific psychosocial needs of the children who receive CAR T‐cell therapy and their families. To guide and standardize the psychosocial care offered for patients receiving CAR T‐cell therapy, we propose the following recommendations for addressing psychosocial support.      

An immunohistochemical study of intracranial germ cell tumours

Summary Histologically verified intracranial tumours, mainly germ cell tumours of the pineal and suprasellar regions, were studied immunohistochemically using anti-serum of alpha fetoprotein (AFP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), human placental lactogen (HPL), pregnancy specific -1 glycoprotein (SP-1), glial fibrillary acidic protein (GFAP), S-100 and neuron specific enolase (NSE). In germinomas, HCG positive cells were occasionally demonstrated in cells presenting as syncytiotrophoblastic giant cells (STGC), and GFAP and S-100 positive cells were found in the surrounding gliotic lesions. Teratomas were positive for CEA in their epithelial components. Endodermal sinus tumours were positive for AFP, choriocarcinomas for HCG and SP-1, and embryonal carcinomas for AFP, HCG and SP-1. HCG and SP-1 positive cells were demonstrated in STGC. As for the relationship between serum AFP level and tissue localization, many cases presenting a serum AFP level exceeding 220 ng/ml were positive for AFP in tumour tissue.