3,841 research outputs found

    Implementing a tenofovir-based first-line regimen in rural Lesotho: clinical outcomes and toxicities after two years.

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    The latest World Health Organization guidelines recommend replacing stavudine with tenofovir or zidovudine in first-line antiretroviral therapy in resource-limited settings. We report on outcomes and toxicities among patients on these different regimens in a routine treatment cohort in Lesotho

    An Evaluation of Commonly Used Surrogate Baseline Creatinine Values to Classify AKI During Acute Infection.

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    INTRODUCTION: Classification of acute kidney injury (AKI) requires a premorbid baseline creatinine, often unavailable in studies in acute infection. METHODS: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min. RESULTS: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85. CONCLUSION: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology

    Evaluation of Canine Pancreas-Specific Lipase Activity, Lipase Activity, and Trypsin-Like Immunoreactivity in an Experimental Model of Acute Kidney Injury in Dogs.

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    BackgroundDiagnosis of pancreatitis in dogs is complicated by extrapancreatic disorders that can alter the results of laboratory tests. Extrapancreatic disorders can also affect the diagnosis of exocrine pancreatic insufficiency (EPI). The effects of acute kidney injury (AKI) on pancreas-specific lipase activity (Spec cPL(®) Test), serum lipase activity and trypsin-like immunoreactivity (TLI) in dogs have not been evaluated.Hypothesis/objectivesSerum Spec cPL, lipase activity, and TLI concentrations will increase secondary to decreased kidney function.AnimalsFive purpose-bred dogs.MethodsExperimental prospective study. Gentamicin was used to induce AKI in 5 purpose-bred dogs. Serum samples were collected for measurement of creatinine, Spec cPL, lipase activity and TLI over 60 days, during both induction of, and recovery from, AKI.ResultsAll dogs developed and recovered from AKI. Six of 52 (12%) serum Spec cPL concentrations were increased (2 in the equivocal zone and 4 consistent with pancreatitis) in 2 of 5 (40%) dogs. Two of 51 (4%) serum lipase activity values were increased in 2 of 5 dogs. Serum TLI was increased above the reference range in 17 of 50 (34%) samples in 3 of 5 dogs. For all biomarkers, there was no consistent correlation with increases in serum creatinine concentration.Conclusions and clinical importanceDecreased renal excretion during experimental AKI did not cause consistent and correlated increases in serum Spec cPL, lipase activity, or TLI in this cohort of dogs

    High serum immunoglobulin g and m levels predict freedom from adverse cardiovascular events in hypertension: a nested case-control substudy of the Anglo-Scandinavian cardiac outcomes trial

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    Aims: We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination. Methods and Results: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5 years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p < 0.0001; IgM 0.83[0.75,0.93], p = 0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p < 0.0001, IgM OR 0.81 (0.71,0.93); p = 0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index. Conclusion: High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension

    Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

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    Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

    Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals.

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    BackgroundHIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals.Methods and resultsWe studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all).ConclusionIn HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death

    Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals

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    Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Main Outcomes and Measures: Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. Results: The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. Conclusions and Relevance: In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved
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