Evaluation of cure rate in patients with hepatitis C virus completing shortened courses of treatment.

BACKGROUND: Guidelines recommend treatment with direct-acting antivirals for a minimum duration of 8 weeks in all patients with hepatitis C virus. Minimizing treatment duration is desirable because of decreased cost and increased adherence. Studies with treatment durations of less than 8 weeks have conflicting data. OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of hepatitis C treatment in patients who did not complete the guideline-recommended duration of therapy. METHODS: This was a retrospective, observational case series of patients with hepatitis C virus treated with 7 weeks or less of direct-acting antivirals between November 1, 2017 and July 31, 2019 at a large, academic medical center. The primary end point was cure, defined as sustained virologic response at 12 weeks after the end of treatment. Secondary end points included average duration of therapy, direct-acting antiviral used, and reason for early discontinuation. RESULTS: Of the 472 patients treated, 13 met criteria for inclusion. Sustained virologic response was achieved in 61.5% of the patients. Two patients (15.3%) were not cured, and 3 patients (23.1%) were lost to follow-up. Median duration of therapy was 4 weeks. All patients who received at least 4 weeks of therapy and remained in care were cured. CONCLUSION: In situations in which patients inadvertently stop hepatitis C treatment early, there is still the possibility of cure. Further studies are needed to determine which patient population may benefit from a shorter duration of therapy.

Impact of anaemia at discharge following colorectal cancer surgery.

OBJECTIVES: Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. METHODS: A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. RESULTS: A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0-200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5-11] vs. 6 [5-8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04-2.5), p = 0.034). CONCLUSION: Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival.

Uncovering biosynthetic relationships between antifungal nonadrides and octadrides.

Maleidrides are a class of bioactive secondary metabolites unique to filamentous fungi, which contain one or more maleic anhydrides fused to a 7-, 8- or 9- membered carbocycle (named heptadrides, octadrides and nonadrides respectively). Herein structural and biosynthetic studies on the antifungal octadride, zopfiellin, and nonadrides scytalidin, deoxyscytalidin and castaneiolide are described. A combination of genome sequencing, bioinformatic analyses, gene disruptions, biotransformations, isotopic feeding studies, NMR and X-ray crystallography revealed that they share a common biosynthetic pathway, diverging only after the nonadride deoxyscytalidin. 5-Hydroxylation of deoxyscytalidin occurs prior to ring contraction in the zopfiellin pathway of Diffractella curvata. In Scytalidium album, 6-hydroxylation - confirmed as being catalysed by the α-ketoglutarate dependent oxidoreductase ScyL2 - converts deoxyscytalidin to scytalidin, in the final step in the scytalidin pathway. Feeding scytalidin to a zopfiellin PKS knockout strain led to the production of the nonadride castaneiolide and two novel ring-open maleidrides.

Impact of a transitions of care pilot service established by pharmacy residents within an academic medical center.

OBJECTIVES: The impact of a pharmacy postgraduate year (PGY)-2 resident-led transitions of care (TOC) pilot service targeting patients with chronic obstructive pulmonary disorder (COPD) and heart failure (HF) was evaluated in terms of 30-day hospital readmissions (primary objective) at the University of Louisville Hospital (ULH) and 30-day emergency department (ED) visits at ULH (secondary objective). SETTING: The study was conducted at an urban academic teaching hospital. PRACTICE DESCRIPTION: Before this pilot service, there were no formal TOC services for patients at high risk for readmission to ULH. PRACTICE INNOVATION: The TOC pilot service providing coverage 16 h/week included patients aged at least 18 years admitted to the ULH internal medicine team with a primary or secondary diagnosis of COPD or HF. Patients to be discharged to a location other than home or who could not be contacted after discharge were excluded. The service consisted of pharmacist-patient interactions before discharge; within 72 hours after discharge, over the telephone; and 7-14 days after discharge, in person. EVALUATION: Data were collected by retrospective chart review from patients enrolled between November 2017 and October 2018. For comparison, a computer-generated report identified patients who met the criteria for the pilot service but could not be enrolled. RESULTS: Of the 23 patients enrolled in the TOC pilot service, none required readmission to ULH within 30 days, compared with 12.3% of all other eligible patients. Similarly, no patients enrolled in the TOC pilot service presented to the ED within 30 days after discharge, compared with 18.6% of the comparator group. Completion rates of postdischarge follow-up were 65.2% for the telephone call and 52.2% for the clinic visit. CONCLUSION: PGY-2 ambulatory care pharmacy residents implemented a new TOC service that contributed to lower rates of 30-day readmissions and ED visits than those for other eligible patients.

Safety and efficacy of dolutegravir in hemodialysis.

With the increasing incidence of chronic kidney disease in patients with human immunodeficiency virus (HIV), the number of HIV-infected patients requiring hemodialysis has also increased. Dolutegravir is an integrase inhibitor that is a common component of HIV treatment regimens. Currently, there is no guidance regarding the use of dolutegravir in patients requiring hemodialysis. Therefore, we sought to evaluate the clinical correlates of safe and effective use of dolutegravir in hemodialysis. This was a retrospective cohort analysis of patients receiving dolutegravir and hemodialysis for at least six months at a single academic HIV medical clinic. The primary safety outcome was discontinuation of dolutegravir due to an adverse effect. The primary efficacy outcome was viral suppression six months after being on dolutegravir and hemodialysis simultaneously. Ten patients received dolutegravir while receiving hemodialysis for six months. No patients discontinued the medication during the six months. Eighty percent of the patients were virally suppressed at six months with 62.5% of those suppressed maintaining suppression and 37.5% achieving suppression over the course of the six months. In a retrospective review of ten patients receiving dolutegravir while on hemodialysis for at least six months, dolutegravir was generally safe and effective for use at standard dosages.

Using Hand Signs to Teach HIV Medications.

Objective. To describe an innovative active learning strategy that uses students' hands to facilitate learning and retention of major concepts related to nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs). Methods. Students wrote the names of the NRTIs on their fingers, then an interactive activity used a variety of hand signs to teach the drugs. Focus groups were conducted with a total of 20 students one year after being exposed to the new teaching strategy. Students were asked five knowledge-based questions related to the subject matter to assess retention of the material. Results. On average, students answered 64% of the questions correctly. Most students (95%) used their hands to answer the knowledge-based questions. There was a statistically significant association between using hands to answer the question and answering the question correctly. When asked which active learning method was most effective, 14 (70%) participants reported "hands." Conclusion. Using students' hands was well received by this cohort of students. More research is needed to determine if this active learning method could be considered for use in other disease states to help students learn complex medications with many nuances.

Motivations that maintain substance use among individuals with psychotic disorders.

This study quantitatively examined reasons for substance use among individuals with psychotic disorders and explored the relationship of these reasons to substance use problems and dependence. Sixty-nine people with psychotic disorders were interviewed using a battery of questionnaires called the Substance Use Scale for Psychosis (SUSP). Symptoms and medication side effects were also measured. A factor analysis revealed similar motives for substance use (mostly alcohol and cannabis use) as in the general population: "enhancement," "social motives," "coping with unpleasant affect," and "conformity and acceptance." A fifth factor, "relief of positive symptoms and side effects," demonstrated limited reliability. "Coping" and "enhancement" motives were found to lead to substance use problems and dependence. Mediator analysis indicated that worse symptoms lead to stronger motives for substance use, which in turn lead to stronger psychological dependence on that substance. These findings have the potential to inform effective treatment for substance use in psychosis.