Publications

BACKGROUND

To reduce unnecessary ambulatory gastroenterology (GI) visits and increase access to GI care, San Francisco Health Network gastroenterologists and primary care providers implemented guidelines in 2013 that discharged certain patients back to primary care after endoscopy with formal written recommendations. This study assesses the longer-term impact of this policy on GI clinic access, workflow, and provider satisfaction.

METHODS

An email-based survey assessed gastroenterologist and primary care provider (PCP) opinions about the discharge process. Administrative data and chart review were used to assess clinic access, intervention fidelity, and re-referral rates.

RESULTS

102/299 (34%) of PCPs and 5/7 (71%) of gastroenterologists responded to the survey. 74% of PCPs and 100% of gastroenterologists were satisfied or very satisfied with the discharge process. 80% of gastroenterologists believed the discharge process decreased their workload, while 53.5% of primary care providers believed it increased their workload. 6.7% of patients discharged to primary care in 2013 had re-referrals to GI. Wait time for the third-next-available new outpatient GI clinic appointment had previously decreased from 158 days (2012, pre-intervention) to 74 days (2013, post-intervention). In 2015, wait time was 19 days (p < 0.001 for 2012 vs. 2015).

CONCLUSIONS

Primary care providers and gastroenterologists are satisfied with an intervention to discharge patients from gastroenterology to primary care after certain endoscopic procedures, although this conclusion is limited by a relatively low PCP survey response rate. Discharging appropriate patients using consensus criteria from the gastroenterology clinic was instrumental in sustainably reducing clinic wait times with low re-referral rates.

Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4 thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs. In addition, CD40-deficient DCs failed to fully mature upon cognate interaction with CD4 thymocytes in vitro and failed to differentiate them into Treg cells to a sufficient number. These findings suggest that tDCs mature and potentiate Treg cell development in feedback response to self-reactive CD4 thymocytes.

AIM

The aim of this study was to study potential cytochrome P450 (CYP) induction by dicloxacillin.

METHODS

We performed an open-label, randomized, two-phase, five-drug clinical pharmacokinetic cocktail crossover study in 12 healthy men with and without pretreatment with 1 g dicloxacillin three times daily for 10 days. Plasma and urine were collected over 24 h and the concentration of all five drugs and their primary metabolites was determined using a liquid chromatography coupled to triple quadrupole mass spectrometry method. Cryopreserved primary human hepatocytes were exposed to dicloxacillin for 48 h and changes in gene expression and the activity of CYP3A4, CYP2C9, CYP2B6 and CYP1A2 were investigated. The activation of nuclear receptors by dicloxacillin was assessed using luciferase assays.

RESULTS

A total of 10 days of treatment with dicloxacillin resulted in a clinically and statistically significant reduction in the area under the plasma concentration-time curve from 0 to 24 h for omeprazole (CYP2C19) {geometric mean ratio [GMR] [95% confidence interval (CI)]: 0.33 [0.24, 0.45]}, tolbutamide (CYP2C9) [GMR (95% CI): 0.73 (0.65, 0.81)] and midazolam (CYP3A4) [GMR (95% CI): 0.54 (0.41, 0.72)]. Additionally, other relevant pharmacokinetic parameters were affected, indicating the induction of CYP2C- and CYP3A4-mediated metabolism by dicloxacillin. Investigations in primary hepatocytes showed a statistically significant dose-dependent increase in CYP expression and activity by dicloxacillin, caused by activation of the pregnane X receptor.

CONCLUSIONS

Dicloxacillin is an inducer of CYP2C- and CYP3A-mediated drug metabolism, and we recommend caution when prescribing dicloxacillin to users of drugs with a narrow therapeutic window.

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on "Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease" (Ravenna, October 27-28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.