Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

Alvan Feinstein and the art of consulting: how to define a research question

When thinking of a new study, the most important task is to define its goals and to choose a design to match those goals. Alvan Feinstein described how he went about consulting others on defining a research question in his book, “Clinical Epidemiology, the Architecture of Clinical Research.” In this paper, the author reminisces about how he learned and tried to apply those principles.     

A new method for oral administration of nystatin in paediatric burn patients

A new method for the topical administration of an antimycotic agent—nystatin—to the oral mucosa is described. The commercially available forms of this drug have a bitter, unpleasant taste, and as a result, are normally not well tolerated by paediatric patients. The new formulation involves mixing nystatin oral suspension with one of the commercially available presweetened soft drink mixes. The resultant mixture is then frozen in the form of popsicles. This reformulation has the advantage of being readily accepted by the child and also provides an increased time of exposure in the oral cavity. In vitro studies validated and quantified the antimycotic action of both the original oral suspension and the new formulation. The new formulation provides a preferable method for the administration of nystatin to paediatric burn patients and may be useful for the administration of other unpalatable drugs to children as well as adults.     

Comparison of Charlson comorbidity index and Kaplan–Feinstein index in patients with stage I lung cancer after surgical resection

Objective: We sought to determine whether Charlson comorbidity index (CCI) or Kaplan–Feinstein index (KFI) is a better predictor of prognosis in patients with stage I NSCLC after surgical resection. Methods: A retrospective study of medical records of 426 patients with stage I lung cancer having complete surgical resection from 1995 to 2000 was performed. Data collected included age, gender, smoking history, resection type, pleural invasion status, and tumor type and size. Comorbidity score was determined using Charlson comorbidity index and Kaplan–Feinstein index. Both univariate and multivariate analyses were used to evaluate prognostic factors. Results: Three hundred and twenty-eight male (76.99%) and 98 female (23.01%) patients had a mean age of 67.07 years (range 19–88 years). Median duration of follow-up was 60.32 months. Total follow-up rate was 95.1%. Distribution of CCI score was: 0, 236 (55.40%); 1, 112 (26.29%); ≥2, 78 (18.31%). Overall KFI score was: none, 247 (57.98%); mild, 126 (29.58%); moderate, 43 (10.09%); and severe, 10 (2.35%). In univariate analyses, patients aged ≥65 years, male, smokers, CCI score ≥2, extensive resection and pathological stage IB cancer had poorer 5-year survival. In multivariate logistic regression analysis, age ≥65 years, pneumonectomy, CCI score ≥2, and stage IB cancer were independent prognostic factors for poorer 5-year survival. Conclusions: Patients with CCI ≥2 had higher perioperative mortality and death from non-cancer causes after surgery compared to patients with CCI <2. However, KFI score had no impact on operative mortality and non-cancer death during follow-up.     

No creative medical science without humor

In his time with the Journal of Clinical Epidemiology and before, Dr. Alvan Feinstein espoused a philosophy of the study of epidemiology as a beneficial, valid science. Not only was Feinstein somewhat of a nonconformist in the field of epidemiology, he had a self-denigrating sense of humor as well. This sense of humor can be showcased by taking a look at one of the articles he approved for publication, which could be retitled as “The Finster Saga.”     

Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents

To facilitate the passage of echo contrast agents through the microcirculation and the echocardiographic study of myocardial perfusion, ultrasonic energy (sonication) was employed to produce contrast agents consisting of relatively uniform, stable and small (less than 10 mu diameter) gaseous microbubbles suspended in liquid solutions. The size and persistence of the microbubbles was verified by light microscopy and an in vitro system were employed for comparative assessment of peak echo amplitude and echo persistence characteristics of various contrast agents. The study indicated that although a variety of hand-agitated and sonicated contrast agents provided satisfactory echo intensities, sonication was clearly superior to the hand-agitation method, because sonication produced smaller, more uniform and more stable microbubbles that may be suitable for myocardial contrast echocardiography. It is concluded that of the contrast agents examined, sonicated solutions of sorbitol (70%) and dextrose (70%) appeared to have particular potential because of the small sizes of the microbubbles (6 +/- 2 and 8 +/- 3 mu, respectively) and their prolonged in vitro persistence. The use of sonication to produce standardized, small and stable microbubbles should facilitate physiologic passage of the contrast agent through the capillary beds and allow two-dimensional imaging of the left heart myocardium during right-sided, aortic root, coronary sinus or intracoronary contrast injections.     

Clinical epidemiology. what,who, and whither

Clinical epidemiology, the what, was introduced by John Paul in 1938, as a new basic science for preventive medicine. Its definition subsequently took on a more bedside tone, but continues to be adapted to the needs of its practitioners. Clinical epidemiology, the who, centers on Alvan Feinstein and the way that he led the field and nurtured so many of its practitioners. Clinical epidemiology, the whither, describes its more recent development and its impact on five evolutions and revolutions: in evidence generation, its rapid critical appraisal, its efficient storage and retrieval, evidence-based medicine, and evidence synthesis.