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Jennings Vincent posted an update 6 months, 2 weeks ago
BACKGROUND Refractory hypertension (RfHTN), a phenotype of antihypertensive treatment failure, is defined as uncontrolled automated office BP ≥130/80 mmHg and awake ambulatory BP ≥130/80 mmHg on ≥5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist. Previous studies suggest that RfHTN is attributable to heightened sympathetic tone. The current study tested whether reserpine, a potent sympatholytic agent, lowers BP in patients with RfHTN. METHODS Twenty-one out of 45 consecutive patients with suspected RfHTN were determined to be fully adherent with their antihypertensive regimen. Seven patients agreed to participate in the current clinical trial with reserpine and six patients completed the study. Other sympatholytic medications, such as clonidine or guanfacine were tapered and discontinued before starting reserpine. Reserpine 0.1 mg daily was administered in an open-label fashion for 4 weeks. All patients were evaluated by AOBP and 24-hour ABP at baseline and after 4 weeks of treatment. RESULTS Reserpine lowered mean systolic and diastolic AOBP by 29.3±22.2 and 22.0±15.8 mmHg, respectively. Mean 24-hr systolic and diastolic ABP was reduced by 21.8±13.4 and 15.3±9.6 mmHg, mean awake systolic diastolic ABP by 23.8±11.8 and 17.8±9.2 mmHg, and mean asleep systolic and diastolic ABP by 21.5±11.4 and 13.7±6.4 mmHg, respectively. CONCLUSIONS Reserpine, a potent sympatholytic agent, lowers BP in patients whose BP remained uncontrolled on maximal antihypertensive therapy, lending support to the hypothesis that excess sympathetic output contributes importantly to the development of RfHTN. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Asymptomatic bacteriuria and pyuria in healthy women often trigger inappropriate antimicrobial treatment, but there is a paucity of data on their prevalence and persistence. METHODS To evaluate the prevalence and persistence of asymptomatic bacteriuria and pyuria in women at high risk for recurrent urinary tract infection, we conducted an observational cohort study of 104 healthy premenopausal women with a history of recurrent urinary tract infection with daily assessments of bacteriuria, pyuria and urinary symptoms over a 3-month period. RESULTS The mean age of participants was 22 and 74% were white. Asymptomatic bacteriuria events (urine cultures with colony count ≥105 CFU/mL of a uropathogen on days with no symptomatic urinary tract infection diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6283 days. Asymptomatic bacteriuria events were most commonly caused by E. coli, which was present on 1.4% of days with median duration one day (range, 1-10). Pyuria occurred in 70 (78%) of 90 evaluable subjects on at least one day and 25% of all days on which no symptomatic urinary tract infection was diagnosed. The positive predictive value of pyuria for E. coli asymptomatic bacteriuria was 4%. CONCLUSIONS In this population of healthy women at high risk for recurrent urinary tract infection, asymptomatic bacteriuria is uncommon and when present rarely lasts more than two days. Pyuria, on the other hand, is common but infrequently associated with bacteriuria or symptoms. These data strongly support recommendations not to screen for or treat asymptomatic bacteriuria or pyuria in healthy, non-pregnant women. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Direct oral anticoagulants (DOACs) have become first-line treatment for venous thrombotic events. DOAC prescribing trends among people with HIV (PWH) are not well described. Co-administration of DOACs with the antiretroviral (ARV) pharmacokinetic boosters ritonavir (RTV) or cobicistat (COBI) may be complicated by pharmacokinetic interactions. METHODS A longitudinal cohort study was conducted using the DC Cohort Database in Washington, D.C., from January 2011-March 2017, to describe oral anticoagulant prescribing among PWH ≥ 18 years old and the prevalence of DOAC use with RTV or COBI. Data collection included demographic and clinical characteristics, ARV and anticoagulant prescriptions and ICD-9/10 diagnosis codes. RESULTS Among 8,315 PWH, there were 236 anticoagulant prescriptions (96 DOAC, 140 warfarin) for 206 persons. PWH prescribed anticoagulants were predominantly Black (82%), male (82%), with a median age at anticoagulant initiation of 56 years. DOAC use increased from 3% of total anticoagulant prescribing in 2011 to 43% in 2016, accounting for 64% of all newly recorded anticoagulant prescriptions by 2016. Nineteen bleeding events were recorded among 16 individuals. Despite the FDA label recommendation to avoid rivaroxaban with boosted ARVs, 41% remained on boosted ARVs after rivaroxaban initiation. CONCLUSION DOAC use increased substantially in PWH by 2016. Although rivaroxaban is not recommended with RTV or COBI, concomitant use was recorded in 41% of rivaroxaban recipients in this cohort. As DOAC usage increases, clinicians need to be aware of potential DOAC-ARV interactions in order to select the most appropriate oral anticoagulant and monitoring plan for PWH. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.Macrophages are heterogeneous and plastic, and play several diverse functions in immune responses. Emerging data provide evidence of multiple roles for metabolic pathways in the control of macrophage effector functions. The diverse functions of macrophages are categorized into two main subsets classical activated macrophages (M1) and alternative activated macrophages (M2). M1 macrophages secrete pro-inflammatory cytokines and reactive oxygen species and migrate into inflamed sites as a part of host defenses. Ebselen price On the other hand, M2 macrophages are involved in immune homeostasis by producing anti-inflammatory cytokines and phagocytosing apoptotic cells. Metabolic reprogramming of environmental or cellular nutrients such as glucose, lipids, and amino acids supports this diversity. Mechanistically, the mammalian target of rapamycin (mTOR) network plays important roles in the effector functions of macrophages by modulating cellular metabolism and regulating gene expression at the transcriptional and translational levels.
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