Lipid lowering efficacy and safety of Ezetimibe combined with rosuvastatin compared with titrating rosuvastatin monotherapy in HIV-positive patients.

BACKGROUND: HIV-infected patients on antiretroviral therapy frequently develop dyslipidemias and, despite therapy with potent lipid-lowering agents, a high percentage does not achieve guideline recommended lipid targets. In this study, we examined the efficacy of combination treatment with a statin and the cholesterol transport blocker, ezetimibe, vs. monotherapy with a statin in HIV-infected patients not achieving lipid goals. METHODS: This was a 12-week, prospective, randomized, open-label clinical trial. Patients were eligible if they had an apolipoprotein B (apoB) >0.80 g/L despite therapy with rosuvastatin 10 mg daily for a minimum of 12 weeks. Patients were randomized to take ezetimibe 10 mg/rosuvastatin 10 mg or rosuvastatin 20 mg for 12 weeks. Percentage and absolute change in apoB (primary outcome), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apoliporpotein A1 (apoA1), apoB/apoA1, TC/HDL-C, atherogenic index of plasma (API), and high-sensitivity C-reactive protein (hsCRP) were compared. Changes in safety parameters (such as AST, ALT, CK) and clinical symptoms were also assessed. RESULTS: Forty-three patients (23 on ezetimibe 10 mg/rosuvastatin 10 mg and 20 on rosuvastatin 20 mg) completed the trial. Baseline characteristics did not differ between the groups. Significant improvements in apoB were seen with both ezetimibe plus rosuvastatin (mean of -0.17 g/L, p < 0.001) and rosuvastatin 20 mg (mean of -0.13 g/L, p = 0.03) treatment groups, but did not differ between groups (p = 0.53). Significant between-group differences were observed for mean TC (-1.01 mmol/L vs. -0.50 mmol/L, p = 0.03), TG (-0.62 mmol/L vs -0.17 mmol/L, p = 0.03), and non-HDL-C (-0.97 mmol/L vs. -0.53 mmol/L, p = 0.03) all in favour of the ezetimibe plus rosuvastatin group. Two patients, both in the rosuvastatin 20 mg group, experienced mild myalgias; neither discontinued the study. CONCLUSIONS: The addition of ezetimibe to rosuvastatin appears to be safe in patients with HIV. Furthermore, the combination of ezetimibe and rosuvastatin improved TG, AIP and non-HDL cholesterol levels more than a dose increase in rosuvastatin in patients with HIV-associated dyslipidemia.

Antimicrobial Pharmacokinetic Considerations in Extracorporeal Membrane Oxygenation.

Critical illness creates challenges for healthcare providers in determining the optimal treatment of severe disease, particularly in determining the most appropriate selection and dosing of medications. Critically ill patients experience endogenous physiologic changes that alter the pharmacokinetics (PKs) of medications. These alterations can be further compounded by mechanical support modalities such as extracorporeal membrane oxygenation (ECMO). Specific components of the ECMO circuit have the potential to affect drug PKs through drug sequestration and an increase in the volume of distribution. Factors related to the medications themselves also play a role. These PK alterations create problems when trying to properly utilize antimicrobials in this patient population. The literature seeking to identify appropriate antimicrobial dosing regimens is both limited and difficult to evaluate due to patient variability and an inability to determine the exact role of the ECMO circuit in reduced drug concentrations. Lipophilic and highly protein bound medications are considered more likely to undergo significant drug sequestration in an ECMO circuit, and this general trend represents a logical starting point in antimicrobial selection and dosing in patients on ECMO support. This should not be the only consideration, however, as identifying infection and evaluating the efficacy of treatments in this population is challenging. Due to these challenges, therapeutic drug monitoring should be utilized whenever possible, particularly in cases with severe infection or high concern for drug toxicity.

Proactive use of QI methodology in consultation-liaison psychiatry to support the opening of a new COVID+ behavioral health inpatient unit during the omicron surge.

Inpatient consultation-liaison (CL) psychiatry teams routinely facilitate the transfer of medically stable patients in behavioral health crisis from the general hospital to inpatient psychiatric units. The COVID-19 pandemic had a significant impact on this process when inpatient psychiatric units were unable to provide care for patients with asymptomatic COVID-19 infection because of infection control concerns in units unable to accommodate isolation precautions. Similar to other disrupted hospital workflows, these clinical handoffs became more complicated by requiring COVID exposed or COVID+ patients in the midst of behavioral health crisis to quarantine or isolate on general hospital units if not otherwise stable for discharge to the community. To better respond to the growing number of patients isolating in the general hospital during the 2022 Omicron surge, we used quality improvement (QI) methodology to illustrate the need to create a COVID+ unit in the inpatient psychiatric hospital to care for the growing cohort of COVID+ patients in psychiatric crisis who were otherwise unable to access traditional psychiatric hospital care because of their isolation status.

Collaborative Care Model Education Opportunities for Psychiatry Trainees: A Narrative Review.

Importance: The Collaborative Care Model (CoCM) is an evidence-based methodology meant to improve access to mental health care, especially in primary care settings. While evidence about the efficacy of CoCM is abundant, literature regarding how CoCM is taught to psychiatry trainees appears to be more limited. As psychiatrists play a key role within the CoCM framework, psychiatry trainee exposure to CoCM skills and concepts is imperative for growth of these services. As psychiatry trainees may one day practice CoCM, we aimed to examine available literature about educational opportunities in CoCM for psychiatry trainees.Observations: While literature was indeed sparse, we identified that CoCM is taught to psychiatry trainees in the form of clinical rotations, didactics, and leadership experiences. Future opportunities are abundant to increase educational opportunities in CoCM for psychiatry trainees.Conclusions and Relevance: Potential future studies should make use of innovative technologies (such as telehealth), should be process-oriented, and should focus more on team dynamics and opportunities for further collaboration with primary care practices within the CoCM framework.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Low Prevalence of Elevated ApoB Levels in Patients with Type 2 Diabetes Not Receiving Lipid-Lowering Therapy.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in people with type 2 diabetes. Apolipoprotein B (apoB) is known to be a better marker of CVD risk than low-density lipoprotein cholesterol (LDL-C). This study investigated apoB levels in people with type 2 diabetes. METHODS: We obtained blood samples from 507 consenting people with type 2 diabetes who were not receiving lipid-lowering medication and who had no previous history of CVD. Subjects were divided into 3 groups: men (M), women <50 years old (W1) and women ≥50 years old (W2). Primary analysis examined lipid parameters, specifically apoB. Secondary analysis involved classifying patients according to the Canadian Diabetes Association's apoB, LDL-C and triglyceride (TG) targets. RESULTS: We found a total mean apoB level of 0.92 g/L. Among patients who failed to achieve the LDL-C target, 28% of M, 39% of W1 and 30% of W2 met the apoB target. The proportions of individuals categorized as being above the LDL-C and apoB targets were significantly different in all 3 groups (p<0.01). When LDL-C was below target and TG was <1.5 mmol/L, 100% of M and W1 and 93% of W2 met the apoB target. CONCLUSIONS: The discordance between the proportions of patients meeting LDL-C and apoB targets may lead to patients being erroneously classified. ApoB and LDL-C correlate very well when TG is <1.5 mmol/L, but not when ≥1.5 mmol/L. Approximately one-third of patients met both LDL-C and apoB goals. Thus, not all patients with type 2 diabetes should be considered to be at a high risk of CVD.

Ezetimibe is effective when added to maximally tolerated lipid lowering therapy in patients with HIV.

To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia. Retrospective analysis of lipid parameters was conducted for 33 patients with HIV who had been prescribed ezetimibe 10 mg per day. Mean total cholesterol was reduced 21% (p < 0.001). Mean LDL was reduced 35% (p < 0.001). Mean HDL increased 8% (p = 0.038). Mean triglyceride was reduced 34% (p = 0.006). Mean Apolipoprotein B100 was reduced 33% (p = 0.043). No adverse events occurred. Ezetimibe appears safe and effective in patients with HIV when added to maximally tolerated doses of lipid lowering therapy.

Are HIV positive patients resistant to statin therapy?

BACKGROUND: Patients with HIV are subject to development of HIV metabolic syndrome characterized by dyslipidemia, lipodystrophy and insulin resistance secondary to highly active antiretroviral therapy (HAART). Rosuvastatin is a highly potent HMG-CoA reductase inhibitor. Rosuvastatin is effective at lowering LDL and poses a low risk for drug-drug interaction as it does not share the same metabolic pathway as HAART drugs. This study sought to determine the efficacy of rosuvastatin on lipid parameters in HIV positive patients with HIV metabolic syndrome. RESULTS: Mean TC decreased from 6.54 to 4.89 mmol/L (25.0% reduction, p < 0.001). Mean LDL-C decreased from 3.39 to 2.24 mmol/L (30.8% reduction, p < 0.001). Mean HDL rose from 1.04 to 1.06 mmol/L (2.0% increase, p = ns). Mean triglycerides decreased from 5.26 to 3.68 mmol/L (30.1% reduction, p < 0.001). Secondary analysis examining the effectiveness of rosuvastatin monotherapy (n = 70) vs. rosuvastatin plus fenofibrate (n = 43) showed an improvement of 21.3% in TG and a decrease of 4.1% in HDL-C in the monotherapy group. The rosuvastatin plus fenofibrate showed a greater drop in triglycerides (45.3%, p < 0.001) and an increase in HDL of 7.6% (p = 0.08). CONCLUSION: This study found that rosuvastatin is effective at improving potentially atherogenic lipid parameters in HIV-positive patients. The lipid changes we observed were of a smaller magnitude compared to non-HIV subjects. Our results are further supported by a small, pilot trial examining rosuvastatin effectiveness in HIV who reported similar median changes from baseline of -21.7% (TC), -22.4% (LDL-C), -30.1% (TG) with the exception of a 28.5% median increase in HDL. In light of the results revealed by this pilot study, clinicians may want to consider a possible resistance to statin therapy when treating patients with HIV metabolic syndrome.

Gestational diabetes mellitus outcome in 394 patients.

OBJECTIVE: To determine whether women with gestational diabetes mellitus (GDM) and their offspring have pregnancy outcomes and complications of pregnancy that are different from those in the general obstetric population. METHODS: Through medical record coding, we identified women with GDM and a singleton pregnancy with cephalic presentation who delivered at St. Paul's Hospital between January 1, 1995, and December 31, 2001. In total, 394 births were analyzed and their outcomes compared with those of a control group of 100 non-diabetic women with the same gestational age (38 weeks) at delivery. RESULTS: Women with gestational diabetes were of lesser parity (P 0.05), appreciably older (P 0.05), and less likely to be Caucasian (P 0.005) than the general obstetric population. Women with GDM also had a higher risk of Caesarean section (P 0.05), gestational hypertension (P 0.05), and large for gestational age (LGA) deliveries (P 0.005). Of women with GDM, those treated with insulin had a higher incidence of LGA deliveries than those on diet therapy alone. The incidence of respiratory distress syndrome and of need for phototherapy was similar in babies whose mothers had GDM and in those whose mothers did not. CONCLUSION: Although the rate of complications remains low, GDM creates a predisposition to increased maternal and neonatal complications.

Ankle brachial index screening for occult vascular disease is not useful in HIV-positive patients.

Metabolic complications common to the HIV-positive population may increase the risk for cardiovascular disease. Asymptomatic peripheral arterial disease (PAD) is associated with increased cardiovascular risk. The ankle-brachial pressure index (ABI) is a screening tool commonly used for the detection of asymptomatic PAD. The prevalence of asymptomatic PAD based on ABI in HIV-positive patients is unknown. This study was cross-sectional in design and assessed PAD by measuring the systolic ABI as determined by a handheld 8-MHz Doppler probe with the patient at rest in a supine position. A brief medical history including pertinent risk factors was obtained. One hundred and sixty-seven HIV-positive patients were evaluated (97.6% male; mean age 52.0 years; 31.2% current smokers, 29.4% former smokers, 26.3% diabetes mellitus). Asymptomatic PAD (ABI < or = 0.9) was found in four patients (2.4%, 95% CI: 0.3-4.5%). Smoking was a significant predictor of PAD. Patients with a positive test for PAD had at least two major risk factors for the disease including smoking, a history of disease in another vascular bed, dyslipidemia, diabetes, and hypertension. All patients with a positive test for PAD had a high risk (>20%) for cardiovascular disease according to the Framingham risk score. Three of the four patients with positive tests had previously diagnosed vascular disease (CAD, stroke). Three patients presenting with PAD were evaluated and all had a positive ABI. The prevalence of PAD compared to previous studies on PAD in HIV was low and identified only those patients with high cardiovascular risk based on other features. ABI was not useful in detecting occult vascular disease in HIV-positive patients and offers no additional information to that derived from cardiovascular risk stratification.