Interindividual variability of atorvastatin treatment influence on the MPO gene expression in patients after acute myocardial infarction

Myeloperoxidase (MPO) and C-reactive protein (CRP) may play critical roles in generation of oxidative stress and the development of the systemic inflammatory response. The aim of the study was to determine the effect of atorvastatin therapy on the MPO gene expression and its plasma level in relation to lipids level lowering and an anti-inflammatory response in patients after acute myocardial infarction. The research material was represented by 112 samples. Thirty-eight patients with first AMI receiving atorvastatin therapy (40 mg/day) and followed up for one month were involved in the study. The relative MPO gene expression in peripheral blood mononuclear cells (PBMCs) was examined using RT-qPCR in 38 patients before-, 38 patients after-therapy and in 36 patients as the control group. The plasma concentrations of MPO and serum concentrations of biochemical parameters were determined using commercially available diagnostic tests. After one month of atorvastatin therapy, in 60.5% patients a decrease of MPO gene expression, whereas in 39.5% patients an increase, was observed. The plasma MPO levels behaved in the same way as the MPO gene expression. However, the serum lipids and CRP concentrations were significantly lower after one month of atorvastatin therapy in both groups of patients - with decreased and increased MPO gene expression. Atorvastatin exhibited a different effect on MPO gene expression and its plasma level. Short-term atorvastatin therapy resulted in lipid lowering and anti-inflammatory activity in patients after AMI, independently of its effect on MPO gene expression. The molecular mechanisms of this phenomenon are not yet defined and require further research

Abordagem etnobotânica de Myrtaceae no município de Sete de Setembro, Rio Grande do Sul, Brasil

A etnobotânica é uma área de pesquisa científica multidisciplinar, que tem o intuito de resgatar conhecimentos empíricos de pessoas para com o uso de vegetais em geral. Ainda hoje, o uso de plantas medicinais é uma importante alternativa, não só por resgatar o patrimônio natural e cultural, como também por estimular a população para um maior aproveitamento dos recursos terapêuticos de origem natural. A família Myrtaceae é constituída atualmente por cerca de 150 gêneros e 4630 espécies, encontram-se especialmente distribuídas em regiões tropicais e subtropicais. No entanto, estudos de resgate empírico desta família são raros ou escassos em municípios de pequeno porte, como em Sete de Setembro, por exemplo. Dessa forma, objetivou-se resgatar o conhecimento etnobotânico de moradores, do município de Sete de Setembro, a cerca da família botânica Myrtaceae. Os dados foram coletados de agosto a novembro de 2016, através de entrevistas informais. Ao total foram entrevistados 60 informantes, 30 para zona rural e 30 para a zona urbana. Utilizou-se a técnica de “bola de neve” e “chefe de família”. Foram relatados pelos entrevistados quatro espécies de plantas utilizadas da família Myrtaceae, a Eugenia uniflora L. (Pitangueira), Psidium guajava L. (Goiabeira), Syzyum jambolanum DC (Jambolão) e o Eucalyptus spp. (Eucalipto). O órgão vegetal mais usado das plantas medicinais catalogadas foram as folhas, sendo as mesmas utilizadas na forma de chás

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale & Objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. Study Design: Observational cohort study. Setting & Participants: Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). Exposure: 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. Outcome: Adjudicated ASCVD events after the year 1 study visit. Analytical Approach: We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. Results: There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. Limitations: Data on whether participants were taking a maximally tolerated statin dosage were unavailable. Conclusions: The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin

Lipid testing trends in the us before and after the release of the 2013 cholesterol treatment guidelines

Background: The 2013 ACC/AHA cholesterol treatment guidelines removed the recom-mendation to treat adults at risk of cardiovascular disease to goal levels of low-density lipoprotein cholesterol (LDL-C). We anticipated that the frequency of LDL-C testing in clinical practice would decline as a result. To test this hypothesis, we evaluated the frequency of LDL-C testing before and after the guideline release. Methods: We used the MarketScan® Commercial and Medicare Supplemental claims data (1/1/2007–12/31/2016) to identify four cohorts: 1) statin initiators (any intensity), 2) high-intensity statin initiators, 3) ezetimibe initiators, and 4) patients at very high cardiovascular risk (≥2 hospitalizations for myocardial infarction or ischemic stroke, with prevalent statin use). Rates of LDL-C testing by calendar year quarter were estimated for each cohort. To estimate rates in the absence of a guideline change, we fit a time-series model to the pre-guideline rates and extrapolated to the post-guideline period, adjusting for covariates, seasonality, and time trend. Results: Pre-and post-guideline rates (LDL-C tests per 1,000 persons per quarter) were 248 and 235, respectively, for 3.9 million statin initiators; 263 and 246 for 1.3 million high-intensity statin initiators; 277 and 261 for 323,544 ezetimibe initiators; and 180 and 158 for 42,108 very high-risk patients. For all cohorts, observed post-guideline rates were similar to model-predicted rates. On average, the difference between observed and predicted rates was 8.5 for patients initiating any statin; 2.6 for patients initiating a high-intensity statin; 11.4 for patients initiating ezetimibe, and −0.5 for high-risk patients. Conclusion: We observed no discernible impact of the release of the 2013 ACC/AHA guidelines on LDL-C testing rates. Rather, there was a gradual decline in testing rates starting prior to the guideline change and continuing throughout the study period. Our findings suggest that the guidelines had little to no impact on use of LDL-C testing

Longitudinal Invariance Testing Of The Knee Injury Osteoarthritis Outcome Score For Joint Replacement Scale (KOOS-JR)

# Background The Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) is a seven-item patient reported outcome measure used to assess perceived knee health. Though commonly used, the longitudinal psychometric properties of the KOOS-JR have not been established and further characterization of its structural validity and multi-group invariance properties is warranted. # Purpose The purpose of this study was to evaluate psychometric properties of the KOOS-JR in a large sample of patients who received care for knee pathology. # Study Design Original research. # Methods Longitudinal data extracted from the Surgical Outcome System (SOS) database of 13,470 knee pathology patients who completed the KOOS-JR at baseline, three-months, six- months, and one-year. Scale structure was assessed with confirmatory factor analysis (CFA), while multi-group and longitudinal invariance properties were assessed with CFA-based procedures. Latent group means were compared with statistical significance set at α ≤ .05 and Cohen’s d effect size as d = 0.2 (small), d = 0.5 (medium), and d = 0.8 (large). # Results CFA results exceeded goodness-of-fit indices at all timepoints. Multi-group invariance properties passed test requirements. Longitudinal analysis identified a biased item resulting in removal of item #1; the retained six-item model (KOOS-JR-6) passed longitudinal invariance requirements. KOOS-JR-6 scores significantly changed over time (p ≤ .001, Mdiff = 1.08, Cohen’s d = 0.57): the highest scores were at baseline examination and the lowest at 12-month assessment. # Conclusions The KOOS-JR can be used to assess baseline differences between males and females, middle and older aged adults, and patients receiving total knee arthroplasty or non-operative care. Caution is warranted if the KOOS-JR is used longitudinally due to potential measurement error associated with item #1. The KOOS-JR-6 may be a more viable option to assess change over time; however, more research is warranted. # Level of Evidence 3 © The Author(s

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Use of negative control outcomes to assess the comparability of patients initiating lipid-lowering therapies

Purpose: Clinical trials have demonstrated efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing risk of cardiovascular disease events, but effectiveness in routine clinical care has not been well-studied. We used negative control outcomes to assess potential confounding in an observational study of PCSK9i versus ezetimibe or high-intensity statin. Methods: Using commercial claims, we identified U.S. adults initiating PCSK9i, ezetimibe, or high-intensity statin in 2015–2018, with other lipid-lowering therapy (LLT) use in the year prior (LLT cohort) or atherosclerotic cardiovascular disease (ASCVD) in the past 90 days (ASCVD cohort). We compared initiators of PCSK9i to ezetimibe and high-intensity statin by estimating one-year risks of negative control outcomes influenced by frailty or health-seeking behaviors. Inverse probability of treatment and censoring weighted estimators of risk differences (RDs) were used to evaluate residual confounding after controlling for covariates. Results: PCSK9i initiators had lower one-year risks of negative control outcomes associated with frailty, such as decubitus ulcer in the ASCVD cohort (PCSK9i vs. high-intensity statin RD = −3.5%, 95% confidence interval (CI): −4.6%, −2.5%; PCSK9i vs. ezetimibe RD = −1.3%, 95% CI: −2.1%, −0.6%), with similar but attenuated associations in the LLT cohort. Lower risks of accidents and fractures were also observed for PCSK9i, varying by cohort. Risks were similar for outcomes associated with health-seeking behaviors, although trended higher for PCSK9i in the ASCVD cohort. Conclusions: Observed associations suggest lower frailty and potentially greater health-seeking behaviors among PCSK9i initiators, particularly those with a recent ASCVD diagnosis, with the potential to bias real-world analyses of treatment effectiveness

Dynamics of cinacalcet use and biochemical control in hemodialysis patients: a retrospective New-user cohort design

Abstract Background Cinacalcet is used to treat secondary hyperparathyroidism among hemodialysis patients. Large-scale epidemiologic studies describing patterns of cinacalcet use, effects on parathyroid hormone (PTH), calcium, and phosphorous levels, and predictors of discontinuation have not been previously reported. Methods This retrospective cohort study used a clinical database of a large U.S. dialysis provider (2007–2010) merged with administrative data from the United States Renal Data System. Among new users of cinacalcet with Medicare coverage, trends in PTH, calcium, and phosphorus were measured in 30-day intervals following cinacalcet initiation. Results Seventeen thousand seven hundred sixty-three eligible initiators contributed 111,047 30-day follow-up intervals. Of these, 56 % discontinued cinacalcet by month 4. Of those discontinuing, 76.3 % reinitiated. Mean values of PTH, calcium, and phosphorus decreased to recommended levels within 4 months following initiation. Proximal PTH levels <150 pg/mL were associated with discontinuation: HR = 1.23 (95 % CI: 1.12, 1.36), whereas low calcium (<7.5 mg/dL) was suggestive of an association, HR = 1.09 (95 % CI 0.91, 1.32). Being in the Part D gap period increased discontinuation risk: HR = 1.09 (95 % CI: 1.03, 1.16). Low-income subsidy status decreased discontinuation risk: HR = 0.77 (95 % CI 0.69, 0.86). Predictors of reinitiation included low-income subsidy, HR = 1.32 (95 % CI 1.22, 1.43); higher albumin level, HR = 1.23 (95 % CI 1.10, 1.36) and higher calcium level, HR = 1.26 (95 % CI 1.19, 1.33). Conclusions Substantial and expected declines in laboratory values occurred following cinacalcet initiation. Early discontinuation and reinitiation of cinacalcet were common and may have occurred for clinical and economic reasons

British HIV Association guidelines for the management of tuberculosis in adults living with HIV 2019

The overall purpose of these guidelines is to help physicians manage adults with tuberculosis (TB)/human immunodeficiency virus (HIV) co‐infection. Recommendations for the treatment of TB in HIV‐positive adults are similar to those in HIV‐negative adults. Of note, the term “HIV” refers to HIV‐1 throughout these guidelines