Faculty Bibliography

Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90 ≤ 1μg/ml), including KPC-2-producing ST11 CR-hvKp. Based upon previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a considered therapeutic option against CR-hvKp infections.

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the GI tract. Fine needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS: This is a multicenter, prospective randomized clinical trial from six large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS: After enrollment, 135 patients were randomized to FNA (49.3%) and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n=210; 76.6%), lymph nodes (n=46, 16.8%), submucosal tumors (n=18, 6.6%). Final diagnosis was malignancy (n=192, 70.1%), reactive lymphadenopathy (n=30, 11.0%), and spindle cell tumors (n=24, 8.8%). FNA had a diagnostic yield of 91.1% compared to 88.5% for FNB (p=0.48). There was no difference between FNA and FNB when stratified by the presence of on-site cytopathology or by type of lesion sampled A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSION: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. Based on these results, there is no significant difference in the performance of FNA compared to FNB in the cytological diagnosis of solid lesions adjacent to the GI tract. (ClincalTrials.gov identifier: NCT01698190).

BACKGROUND:Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the pre-analytical phase of the inpatient tacrolimus TDM process at their institution. METHODS:Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted and time distribution plots for each step in the inpatient TDM process were generated. RESULTS:Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 +/- 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within one hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. CONCLUSIONS:Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

Stent thrombosis is a potentially life threatening condition caused by several factors or a combination factors, such as resistance to platelet agents and type of anticoagulation used as well as stent types. We report a case of acute thrombosis and discuss potential areas of intervention with literature review.

PURPOSE:Access to comparative information on hospitals' quality of cancer care is limited. Patients' interest in using this information when selecting a hospital for cancer surgery and the specific data they would desire are unknown. This study gauges patients' demand for comparative information on hospitals' quality of cancer surgery. METHODS:We conducted a cross-sectional, national survey of 3,334 US residents who had received cancer surgery. The outcomes were patients' reported likelihood of using a list of best hospitals for cancer surgery and patients' reported interest in information about specific clinical outcomes, including 4-year survival after surgery, 30-day mortality after surgery, and rate of complications from surgery. RESULTS:Two thirds of patients (68%) reported being actively involved in selecting a hospital for their surgery, and two thirds (65%) reported that their physician was involved in or made this decision. When asked what information might have helped them to choose a hospital, participants identified the hospital's reputation (55%), patient satisfaction (44%), and the number of cancer surgeries performed at the hospital (36%). Approximately three quarters (73%) reported being likely to use a list of best hospitals for cancer surgery when selecting a hospital. Approximately 40% expressed interest in having information on at least one clinical outcome. CONCLUSION:Widespread interest exists among patients with cancer for comparative information on hospital quality as well as on clinical outcomes and hospitals' reputation for cancer surgery. Policy reforms and additional research should address the unmet need for transparent, comprehensive data on the quality of hospitals' cancer care.