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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0002-8703(00)90313-2 Byline: Giovanni Gambassi, Daniel E. Forman, Kate L. Lapane, Vincent Mor, Antonio Sgadari, Lewis A. Lipsitz, Roberto Bernabei Abstract: Background Increasing prevalence, use of health services, and number of deaths have made congestive heart failure (CHF) a new epidemic in the United States. Yet there are no adequate data to guide treatment of the more typical and complex cases of patients who are very old and frail. Methods Using the SAGE database, we studied the cases of 86,094 patients with CHF admitted to any of the 1492 long-term care facilities of 5 states from 1992 through 1996. We described their clinical and functional characteristics and their pharmacologic treatment to verify agreement with widely approved guidelines. We evaluated age- and sex-related differences, and we determined predictors of receiving an angiotensin-converting enzyme (ACE) inhibitor by developing a multiple logistic regression model. Results The mean age of the population was 84.9 [+ or -] 8 years. Eighty percent of the patients 85 years of age or older were women. More than two thirds of patients underwent frequent hospitalizations related to CHF in the year preceding admission to a long-term care facility. Coronary heart disease and hypertension were the most common causes. Half of the patients received digoxin and 45% a diuretic, regardless of background cardiovascular comorbidities. Only 25% of patients had a prescription for ACE inhibitors. The presence of cardiovascular comorbidity, already being a recipient of a large number of medications, a previous hospitalization for CHF, and admission to the facility in recent years were associated with an increased likelihood of receiving an ACE inhibitor. The presence of severe physical limitation was inversely related to use of ACE inhibitors, as were a series of organizational factors related to the facilities. Conclusions Patients in long-term care who have CHF little resemble to those enrolled in randomized trials. This circumstance may explain, at least in part, the divergence from pharmacologic management consensus guidelines. Yet the prescription of ACE inhibitors varies significantly across facilities and depends on organizational characteristics. (Am Heart J 2000;139:85-93.) Author Affiliation: Rome, Italy; Providence, RI; and Boston, Mass From the.sup.aIstituto di Medicina Interna e Geriatria, Universita Cattolica del Sacro Cuore, Rome..sup.bCenter for Gerontology and Health Care Research and.sup.cDepartment of Community Health, Brown University Medical School, Providence..sup.dDivision of Cardiology, Department of Medicine, Miriam Hospital, Providence; and.sup.eHebrew Rehabilitation Center for Aged, Harvard Medical School, Boston Article History: Received 3 September 1998; Accepted 11 June 1999 Article Note: (footnote) [star] Members of the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) Study Group are listed in the acknowledgment. , [star][star] Funded in part by the National Institute on Aging through grant no. 11624 and Health Care Financing Administration through grant no. 17C90428 to University of Michigan with Brown University as a subcontractor. , a Reprint requests: Kate Lapane, MD, Center for Gerontology and Health Care Research, Brown University, Box G-B222, 171 Meeting St, Providence, RI 02912. E-mail: Kate_Lapane@brown.edu , aa 0002-8703/2000/$12.00 + 0 4/1/101108

Byline: Michael W. Rich, Kristin Brooks, Priya Luthera Abstract: The objectives of this study were to assess current practice patterns in pharmacotherapy for congestive heart failure at an academic medical center and to analyze temporal trends in management of congestive heart failure from 1990 to 1995. Records of all patients discharged from the hospital in 1990 or 1995 with a primary diagnosis of congestive heart failure who also underwent echocardiography were found by a search of the hospital's medical records database. All charts were reviewed, and relevant clinical data, including all discharge medications, were recorded. On the basis of echocardiograms, patients were classified as having preserved or impaired left ventricular systolic function (estimated ejection fraction [greater than or equal to]45% versus Author Affiliation: St. Louis, Mo Article History: Received 4 February 1997; Accepted 12 August 1997 Article Note: (footnote) [star] From the aGeriatric Cardiology Section, Division of Cardiology, Barnes-Jewish Hospital at Washington University, and bDepartment of Pharmacy, Barnes-Jewish Hospital, St. Louis College of Pharmacy., [star][star] Supported by a grant from Merck & Co., a Reprint requests: Michael W. Rich, MD, Director, Geriatric Cardiology Program, Barnes-Jewish Hospital, North Campus, 216 S. Kingshighway, St. Louis, MO 63110., aa 0002-8703/98/$5.00 + 0 4/1/86046

A novel multispecific organic anion transporting polypeptide (oatp2) has been isolated from rat brain. The cloned cDNA contains 3,640 bp. The coding region extends over 1,983 nucleotides, thus encoding a polypeptide of 661 amino acids. Oatp2 is homologous to other members of the oatp gene family of membrane transporters with 12 predicted transmembrane domains, five potential glycosylation, and six potential protein kinase C phosphorylation sites. In functional expression studies in Xenopus laevis oocytes, oatp2 mediated uptake of the bile acids taurocholate ([K.sub.m] [approximately equal to] 35 [[micro]molar]) and cholate ([K.sub.m] [approximately equal to] 46 [[micro]molar]), the estrogen conjugates 17[Beta]estradiol-glucuronide ([K.sub.m] [approximately equal to] 3 [[micro]molar]) and estrone-3-sulfate ([K.sub.m] [approximately equal to] 11 [[micro]molar]), and the cardiac gylcosides ouabain ([K.sub.m] [approximately equal to] 470 [[micro]molar]) and digoxin ([K.sub.m] [approximately equal to] 0.24 [[micro]molar]). Although most of the tested compounds are common substrates of several oatp-related transporters, high-affinity uptake of digoxin is a unique feature of the newly cloned oatp2. On the basis of Northern blot analysis under high-stringency conditions, oatp2 is highly expressed in brain, liver, and kidney but not in heart, spleen, lung, skeletal muscle, and testes. These results provide further support for the overall significance of oatps as a new family of multispecific organic anion transporters. They indicate that oatp2 may play an especially important role in the brain accumulation and toxicity of digoxin and in the hepatobiliary and renal excretion of cardiac glycosides from the body.

The three-dimensional structures of the antigen-binding fragment of the anti-digoxin monoclonal antibody do not alter in the process of forming the complex. Digoxin responds to the antibody heavy chain, carbohydrate groups are open to solvent and the lactonic ring is located deep in the combining site. The 26-10 digoxin complex is special with specificity and high affinity arising from shape complementarity.