BackgroundProprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low‐density lipoprotein cholesterol (LDL‐C) and improve outcomes in the general population. HIV‐infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and ResultsWe studied 567 participants from a clinic‐based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL‐C level was 100 mg/dL (IQR 77–124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL‐C, and high‐density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV‐coinfected patients versus controls (95% CI 9–34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3–20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8–33%, P=0.001). Interleukin‐6 levels increased in a stepwise fashion from controls (lowest) to HIV‐infected to HIV/HCV‐coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).ConclusionsDespite having lower LDL‐C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin‐6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.

OPAT with β-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures.

Background—Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque.Methods and Results—Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39–49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; P<0.001), in those with plaque (32% versus 17%; P=0.0002), and in those without plaque (16% versus 7%; P=0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05–1.33; P=0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02–4.08; P=0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors.Conclusions—Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins.

To the authors' knowledge, no other study has examined the impact of reconciliation on types and prevalence of medication errors at hospital discharge. The focus on intravenous antibiotics as a class of high-stakes medications with serious risks to patient safety during error events highlights the clinical importance of the findings. Electronic medication reconciliation may be an important tool in efforts to improve patient safety.

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Background. β-lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT.Methods. Retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between 2009 and 2011.Demographics, infections, antibiotics, outcomes and adverse events (AE) were recorded. Cumulative incidence of first occurrence of 30-day readmission, antibiotic switch, or treatment success for each drug was compared using competing risks analysis. Event times were censored at 60 days.Results. 408 patients were identified (cefazolin N = 36, ceftriaxone N = 109, ertapenem N = 130, oxacillin N = 133). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 63.9, ceftriaxone 74.9, ertapenem 75.5, oxacillin 55.1 %; chi-square p < 0.001). Thirty-day all-cause readmissions were similar (cefazolin 22.2, ceftriaxone 12.4, ertapenem 18.2 and oxacillin 13.7%; p = 0.39; figure 1), as were readmissions for worsening infections or AE (cefazolin 5.6, ceftriaxone 3.7, ertapenem 6.1 and oxacillin 5.3%). Antibiotic switch rates were significantly higher for oxacillin compared to others (oxacillin 21.4, cefazolin 8.3, ceftriaxone 4.1, ertapenem 1.8 %; p < 0.001). Switches due to AE (figure 2) were more common than treatment failure (figure 3) (n= 31 vs. 7). In 408 OPAT courses, 38 antibiotic switches were accomplished without readmission.Conclusion. OPAT with β-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. By overseeing antibiotic switches, OPAT programs may avoid AE-related readmissions, thus reducing patient morbidity and costs. Readmission avoidance should count towards the value of OPAT programs.