Barriers to treatment of chronic hepatitis C with direct acting antivirals in an urban clinic.

INTRODUCTION AND AIM: Direct-acting antiviral (DAA) agents are highly effective for treatment of chronic hepatitis C virus (HCV) yet access to treatment remains a serious challenge. The aim of this study was to identify barriers to treatment initiation with DAA-containing regimens in an urban clinic setting. MATERIALS AND METHODS: A retrospective cohort of all chronic HCV patients seen in an urban academic practice in Jacksonville, FL, USA from 1/2014 to 1/2017 was analyzed. Baseline characteristics were recorded and a review of medical records was performed to identify barriers to treatment initiation and overall success rates. RESULTS: Two-hundred and forty patients with chronic HCV were analyzed. Fifty-six percent of patients were African-American and 63% were insured through Medicaid/county programs or uninsured. Sixty-nine percent had barriers to initiating antiviral therapy categorized as psychosocial (n=112), provider (n=26), medical (n=20), and insurance-related factors (n=7). The most commonly encountered psychosocial barriers included failure to keep appointments (79/240, 33%), active substance abuse (18/240, 8%), and failure to obtain laboratory testing (11/240, 5%). Overall, only 27% of patients evaluated were initiated on DAA-containing regimens with 18% reaching SVR12 within the 36-month study period. CONCLUSION: In conclusion, only 27% of patients who presented to an urban academic practice with chronic HCV received DAA-containing regimens over a 36-month period. Psychosocial issues were the major barriers to antiviral therapy. These findings illustrate the need for an integrated approach that addresses psychosocial factors as well as comorbidities and adherence to care in order to increase rates of HCV treatment in at risk patients.

Flavopiridol displays preclinical activity in acute lymphoblastic leukemia.

BACKGROUND: New agents are needed for treatment of children with relapsed acute lymphoblastic leukemia (ALL). Based on altered expression of cell cycle regulatory proteins, including frequent p16 (INK4A) and p15 (INK4B) deletions, flavopiridol (FP; Alvocidib) is an attractive agent for relapsed ALL. PROCEDURE: We evaluated the efficacy of FP in ALL cell lines using cell proliferation assays, determined the effects of FP treatment on cell growth and viability in cell lines and patient samples, examined cell cycle kinetics, and evaluated the effect of FP on endogenous cyclin-dependent kinase (CDK) activity, Mcl-1 expression, and RNA polymerase II expression and phosphorylation. RESULTS: ALL cell lines are sensitive to FP. At lower concentrations, FP induces transient G(1)-S cell cycle arrest and modest levels of apoptosis in cell lines. In contrast, a sustained G(1)-S and G(2)-M arrest and substantial apoptosis are observed following exposure to higher FP concentrations. After treatment with FP, ALL cell lines have decreased expression of retinoblastoma protein phosphorylated at serines 795 and 807/811, indicating reduced CDK activity. We also show that ALL cell lines are sensitive to clinically achievable concentrations of FP in medium supplemented with human serum and that FP reduces the expression of Mcl-1 and phosphorylated forms of the C-terminal domain of RNA polymerase II. FP also increases cell death by approximately twofold over baseline in primary ALL blasts. CONCLUSIONS: These data provide a biological rationale for testing FP in relapsed ALL.

Emergency department crowding and time to antibiotic administration in febrile infants.

INTRODUCTION: Early antibiotic administration is recommended in newborns presenting with febrile illness to emergency departments (ED) to avert the sequelae of serious bacterial infection. Although ED crowding has been associated with delays in antibiotic administration in a dedicated pediatric ED, the majority of children that receive emergency medical care in the United States present to EDs that treat both adult and pediatric emergencies. The purpose of this study was to examine the relationship between time to antibiotic administration in febrile newborns and crowding in a general ED serving both an adult and pediatric population. METHODS: We conducted a retrospective chart review of 159 newborns presenting to a general ED between 2005 and 2011 and analyzed the association between time to antibiotic administration and ED occupancy rate at the time of, prior to, and following infant presentation to the ED. RESULTS: We observed delayed and variable time to antibiotic administration and found no association between time to antibiotic administration and occupancy rate prior to, at the time of, or following infant presentation (p>0.05). ED time to antibiotic administration was not associated with hospital length of stay, and there was no inpatient mortality. CONCLUSION: Delayed and highly variable time to antibiotic treatment in febrile newborns was common but unrelated to ED crowding in the general ED study site. Guidelines for time to antibiotic administration in this population may reduce variability in ED practice patterns.

Compliance with outpatient stress testing in low-risk patients presenting to the emergency department with chest pain.

Recent evidence suggests that stress testing prior to emergency department (ED) release in low-risk chest pain patients identifies those who can be safely discharged home. When immediate stress testing is not feasible, rapid outpatient stress testing has been recommended. The objective of this study was to determine compliance rate and incidence of adverse cardiac events in patients presenting to the ED with low-risk chest pain referred for outpatient stress testing. Retrospective chart and social security death index review were conducted in 448 consecutive chest pain patients who presented to a university hospital and level I trauma center between April 30 and December 31, 2007. Patients were evaluated with an accelerated chest pain protocol defined as a 4-hour ED rule out and referral for outpatient stress testing within 72 hours of ED release. Only patients without known cardiac disease, a thrombolysis in myocardial infarction risk score ≤2, negative serial ECGs and cardiac biomarkers, and benign ED course were eligible for the protocol. Primary outcome measures included compliance with outpatient stress testing and documented 30-day incidence of adverse cardiac events following ED release. The social security death index was queried to determine 12-month incidence of all-cause mortality in enrolled patients. Logistic regression analysis of characteristics associated with outpatient stress test compliance was determined and incidence of adverse cardiac events in those who were and were not compliant with outpatient stress testing was compared. Significance was set at P < 0.05. A total of 188 patients (42%) completed outpatient stress testing, but only 27 (6%) completed testing within 72 hours of ED discharge. Compliance was correlated with insurance and race, but not patient age, gender, or thrombolysis in myocardial infarction risk score. No significant differences in adverse cardiac events were documented in patients who did and did not comply with outpatient stress testing. Compliance with outpatient stress testing is poor in low-risk chest pain patients following ED release. Despite poor compliance, the documented incidence of adverse cardiac events in this low-risk cohort was lower than that reported in patients with negative provocative testing prior to ED release.