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Contrast medium use.

Various properties of iodinated contrast media (osmolality, ionic versus nonionic, and viscosity) may contribute to contrast-induced nephropathy (CIN). Therefore, the choice of contrast medium affects the risk for CIN. There is good evidence that low-osmolar contrast media are less nephrotoxic than high-osmolar contrast media in patients at increased risk for CIN who receive intra-arterial iodinated contrast. Current evidence suggests that nonionic isosmolar contrast presents the lowest risk for CIN in patients with chronic kidney disease (CKD), particularly in those patients with diabetes mellitus. Intra-arterial administration of contrast media may be associated with a greater risk for CIN above that observed with intravenous administration. The use of gadolinium or CO(2) as alternative contrast media to avoid the risk of nephrotoxicity cannot be substantiated by clinical trials and therefore cannot be recommended. Most studies show that, within a class, higher volumes (>100 mL) of iodinated contrast medium are associated with a higher risk for CIN. However, in patients at high risk, such as those with CKD and diabetes, even small volumes of contrast medium can have adverse effects on renal function.

Acute Kidney Injury↗

Strategies to reduce the risk of contrast-induced nephropathy.

In view of the clinical importance of contrast-induced nephropathy (CIN), numerous potential risk-reduction strategies have been evaluated. Adequate intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for 3-12 hours before the procedure and continued for 6-24 hours afterward can lessen the probability of CIN in patients at risk. There are insufficient data on oral fluids (as opposed to intravenous volume expansion) as a CIN-prevention strategy. No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing risk for CIN. Prophylactic hemodialysis and hemofiltration have not been validated as effective strategies. The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), ascorbic acid, and prostaglandin E(1) deserve further evaluation. N-acetylcysteine is not consistently effective in reducing the risk for CIN. Fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and l-arginine have not been shown to be effective. Use of furosemide, mannitol, or an endothelin receptor antagonist is potentially detrimental. Nephrotoxic drugs should be withdrawn before contrast administration in patients at risk for CIN.

Acute Kidney Injury↗

High-risk situations and procedures.

With the wider use of imaging and interventional techniques that require the use of iodinated contrast media in seriously ill patients, many clinical situations occur where patients may be at increased risk for contrast-induced nephropathy (CIN). There is little guidance for clinicians in these areas. The aim of this review is to assess the available literature. Acute renal failure is a common complication following coronary artery bypass surgery, and exposure to contrast medium may increase the risk for this condition, although there is insufficient evidence to make a definitive statement. Evidence is also limited for patients with liver disease: in those undergoing transarterial chemoembolization, cirrhosis may be a risk factor for renal failure. There is some evidence that periprocedural hypotension may be a risk factor for CIN after percutaneous coronary intervention, but no published information was identified on the significance of shock or hypotension in other groups of patients. The published evidence on the risk of CIN in renal transplant recipients is inconsistent. In emergency situations, the course of action is usually dictated by clinical circumstances; the renal status of a patient is likely to be unknown and it is important to ensure adequate volume expansion, especially after the procedure. In all clinical situations that are potentially associated with a high risk for CIN, the decision to administer contrast medium is a matter for clinical judgment, based on the clinical status of the patient and the expected benefits of the investigation or procedure.

Acute Kidney Injury↗

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗

Adjuvant chemotherapy in 2005: standards and beyond.

The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with "standard efficacy" (ACx4, CMFx6) and those with "superior efficacy" (FA(E)Cx6, CA(E)Fx6, A(E)-->CMF, TACx6, ACx4--> paclitaxel (P)x4 or docetaxel (D)x4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the "superior" regimens and 5-year benefits reported in taxane trials, including those of a "new" sequential regimen, FECx3--> docetaxelx3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule.

Antineoplastic Combined Chemotherapy Protocols↗

Recommendations of the international guidelines 2000 conference on cardiopulmonary resuscitation and emergency cardiac care: an overview.

The greatest potential for survival of sudden cardiac arrest can be achieved only by providing early intervention using evidence-based therapies that have been studied over time. Emergency cardiac care and the 2000 advanced cardiac life support guidelines encompass all therapies that have been shown to improve outcomes in patients who experience life-threatening events that involve the cardiovascular, cerebrovascular, and pulmonary systems. Early recognition of warning signs, activation of emergency medical systems within the community, basic cardiopulmonary resuscitation, early defibrillation, airway management, and intravenous medication administration are key factors in improving resuscitation outcomes.

Algorithms↗

Intervention strategies for neonatal hypoxic-ischemic cerebral injury.

BACKGROUND: Accumulating evidence points to an evolving process of brain injury after intrapartum hypoxia-ischemia that initiates in utero and extends into a recovery period. It is during this recovery period that the potential for neuroprotection exists. OBJECTIVE: This discussion briefly reviews the cellular characteristics of hypoxic-ischemic cerebral injury and the current and future therapeutic strategies aimed at ameliorating ongoing brain injury after intrapartum hypoxia-ischemia. METHODS: As part of the Newborn Drug Development Initiative, the National Institute of Child Health and Human Development and the US Food and Drug Administration cosponsored a workshop held March 29 and 30, 2004, in Baltimore, Maryland. Information for this article was gathered during that workshop. Literature searches of MEDLINE (Ovid) and EMBASE (1996-2005) were also conducted; search terms included newborn, infant, hypoxia-ischemia, hypoxic-ischemic encephalopathy, asphyxia, pathogenesis, treatment, reperfusion injury, and mechanisms, as well as numerous interventions (ie, therapeutic hypothermia, magnesium, and barbiturates). RESULTS: The acute brain injury results from the combined effects of cellular energy failure, acidosis, glutamate release, intracellular calcium accumulation, lipid peroxidation, and nitric oxide neurotoxicity that serve to disrupt essential components of the cell, resulting in death. Many factors, including the duration or severity of the insult, influence the progression of cellular injury after hypoxia-ischemia. A secondary cerebral energy failure occurs from 6 to 48 hours after the primary event and may involve mitochondrial dysfunction secondary to extended reactions from primary insults (eg, calcium influx, excitatory neurotoxicity, oxygen free radicals, or nitric oxide formation). Some evidence suggests that circulatory and endogenous inflammatory cells/mediators also contribute to ongoing brain injury. The goals of management of a newborn infant who has sustained a hypoxic-ischemic insult and is at risk for injury should include early identification of the infant at highest risk for evolving injury, supportive care to facilitate adequate perfusion and nutrients to the brain, attempts to maintain glucose homeostasis, and consideration of interventions to ameliorate the processes of ongoing brain injury. Recent evidence suggests a potential role for modest hypothermia (ie, a reduction in core body temperature to -34 degrees C) administered to high-risk term infants within 6 hours of birth. Either selective (head) or systemic (body) cooling reduces the incidence of death and/or moderate to severe disability at 18-month follow-up. Additional strategies-including the use of oxygen free radical inhibitors and scavengers, excitatory amino acid antagonists, and growth factors; prevention of nitric oxide formation; and blockage of apoptotic pathways-have been evaluated experimentally but have not been replicated in a systematic manner in the human neonate. Other avenues of potential neuroprotection that have been studied in immature animals include platelet-activating factor antagonists, adenosinergic agents, monosialoganglioside GM1, insulin-like growth factor-1, and erythropoietin. CONCLUSIONS: Much progress has been made toward understanding the mechanisms contributing to ongoing brain injury after intrapartum hypoxia-ischemia. This should facilitate more specific pharmacologic intervention strategies that might provide neuroprotection during the reperfusion phase of injury.

Consensus Statements as Topic↗

Cardiovascular support in preterm infants.

BACKGROUND: Despite increasing investigation in the area of cardiovascular instability in preterm infants, huge gaps in knowledge remain. None of the current treatments for hypotension, including the use of inotropic agents, have been well studied in the preterm population, and data regarding safety and efficacy are lacking. Thus, the labeling information regarding the use of inotropes as therapeutic agents in this population is inadequate. OBJECTIVE: This article reviews the current deficiencies in knowledge with respect to measuring and achieving normal organ perfusion; summarizes the clinical, methodological, and ethical issues to consider when designing trials to evaluate medications for hemodynamic instability in the preterm neonate; and proposes 2 possible trial designs. Unanswered questions and potential obstacles for the systematic study of drugs to treat cardiovascular instability in preterm neonates are discussed. METHODS: The neonatal Cardiology Group was established in 2003 by the US Food and Drug Administration (FDA) and the National Institute of Child Health and Human Development (NICHD) as part of the Newborn Drug Development Initiative. The Cardiology Group conducted a number of teleconferences and one meeting to develop a document addressing gaps in knowledge regarding cardiovascular drugs commonly used in low-birth-weight neonates and possible approaches to investigate these drugs. This work was presented at a workshop cosponsored by the NICHD and the FDA held in March 2004 in Baltimore, Maryland. Information for this article was gathered during this initiative. RESULTS: To develop rational, evidence-based guidelines corroborated by robust scientific data for cardiovascular support in newborns, well-designed and adequately powered pharmacologic studies and clinical trials are needed to evaluate the safety and efficacy of inotropic agents and to determine the short- and long-term effects of these drugs. Trials investigating the currently available and novel therapies for cardiovascular instability in neonates will provide information that can be incorporated into product labeling and a scientific framework for cardiovascular management in critically ill neonates. The Cardiology Group identified and prioritized 2 conditions for investigation of therapeutic options for the management of neonatal cardiovascular instability: (1) cardiovascular instability in preterm neonates; and (2) cardiac dysfunction in neonates after cardiopulmonary bypass surgery. Key research questions in the area of cardiovascular instability in the preterm infant include determining optimal blood pressure (BP) in preterm infants; identifying better measures than BP to determine organ perfusion; optimizing hemodynamic treatments; and clarifying any associations between BP or therapy for low BP and mortality, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and neurodevelopmental outcome. The Cardiology Group concluded that the study of inotropic agents in neonates using outcomes of importance to patients will require a complicated trial design to address the elements discussed. The group proposed 2 clinical trial designs: (1) a placebo-controlled trial with rescue therapy for symptomatic infants; and (2) a targeted BP trial. CONCLUSION: This summary is intended to stimulate and assist future research in the area of cardiovascular support for preterm infants.

Cardiotonic Agents↗

Delivery room resuscitation past, present, and the future.

Delivery room resuscitation guidelines evolved in the late 1980s in the United States, based largely on clinical experience with some supportive experimental evidence. Subsequently over time, there has been an increasing emphasis toward the practice of evidence-based medicine. Despite difficulties in conducting research in the delivery room, several large randomized studies have been undertaken over the past two decades that have provided a scientific basis for some of the new guidelines.

Consensus Statements as Topic↗

Management of cardiovascular disease in the elderly: a review of the Canadian Cardiovascular Society Consensus Conference.

Although Joan and Edward are fictitious characters, it is very likely we have encountered or will encounter patients with similar health concerns and daily life issues. As the population ages and our lifestyles continue to promote the development of cardiovascular disease, there is an increasing need to focus on the best ways to deal with this looming crisis. The CCS recognizes this pressing concern. The publication of the 2002 Consensus Conference assists all practitioners to work with their elderly patients to manage their heart disease most effectively. The CCS also recognizes the need for additional research. Throughout the document there is a continuous call for further study of best practice in the management and treatment of older adults with cardiovascular disease-stay tuned.

Aged↗

Frequently asked questions about medical abortion.

The development of methods of inducing abortion medically (nonsurgically) has created alternative options to make abortion available to women in a variety of health-care settings. Medical abortion is induced with a regimen of mifepristone followed by a prostaglandin analogue. Since its first introduction in the late 1980s, the regimen has undergone some modifications based on research evidence, and, in many countries, clinicians are using regimens that may differ from the one that has been licensed. This causes confusion among providers, also because only a few countries have developed national guidelines for the provision of medical abortion. We approached health care personnel providing abortion services in various countries and asked them to send us questions that they, or their colleagues, might have concerning the clinical practice of medical abortion in the early first trimester (up to 63 days since the first day of the last menstrual period). These questions were sent to experts representing the fields of biomedical and clinical research, clinical practice and family planning, who conducted literature reviews so that, whenever possible, the answers could be based on existing evidence. A consensus meeting was held in Bellagio, Italy, between November 1 and 5, 2004, to review the questions and to discuss the answers. The aim of this article is to provide a brief overview of some of the questions asked and the answers discussed.

Abortifacient Agents, Steroidal↗

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception.

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

Female↗

Background to Eusoma guidelines and statements.

The European Society of Mastology (Eusoma) is committed in writing and diffusing guidelines on Breast Cancer, aiming at harmonising the quality of Breast Cancer care throughout Europe. To achieve this Eusoma organises scientific meetings, "workshops" or "Consensus meeting", inviting European experts from the different disciplines involved in the multidisciplinary management of Breast Cancer patients, to give their contribution in drafting "guidelines" or "consensus statements". In this regard Eusoma Executive Committee members found it appropriate to define the rules to organise its scientific meetings and to write the documents resulting from these meetings, i.e guidelines or statements. This will guarantee an homogeneity in the meeting organisations and in drawing up the scientific documents.

Breast Neoplasms↗