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Early-Stage Pipeline continued Aminocandin Aminocandin is an antifungal that attaches to the cell walls of various fungi, killing the fungi rather then inhibiting their growth, which is the mechanism of many antifungal agents on the market. The drug was licensed in from Aventis. The Company will start a Phase I intravenous trial in 2004. Aminocandin also known as HMR 3270 ; belongs to a class of compounds known as the echinocandins. It is a semisynthetic derivative of echinocandin B, a polypeptide yeast fermentation product with antifungal properties. It is being developed as a broad-spectrum systemic antifungal agent. Echinocandins are inhibitors of the enzyme complex -1, 3-glucan synthase that catalyze the synthesis of 1, 3 + glucan polysaccharides, which are components of the cell walls of fungi. The echinocandins are effective mainly against the Candida and Aspergillus species, which are prominent opportunistic fungi, with possible activity against some other species. All members of the class appear to have similar antifungal efficacies, with possible minor species differences, and are generally well tolerated. The main difference between the echinocandins appears to be pharmacokinetic; their bioavailabilites vary, most likely due to their respective lipid solubility, extent of protein binding, and liver metabolism. None of the echinocandins are sufficiently bioavailable upon oral administration and must be administered intravenously. Pharmacokinetic data specific to aminocandin are not available. There does not appear to be any cross-resistance with the polyene or azole antifungals, their main competitors and a main source of concern for any antibiotic treatment. The main competitors for aminocandin are other echinocandins as well as the azole class of antifungals and amphotericin B. Caspofungin Cancidas, Merck ; is currently marketed in the US for the treatment of various Candida infections as well as Aspergillus invasions, which are refractory or intolerant of other therapies. Micafungin Fujisawa ; is currently marketed in Japan and is awaiting US approval. The azole antifungals are the largest class of antifungal agents and include fluconazole Diflucan, Pfizer ; , ketoconazole Nizoral, McNeil ; , and itraconazole Sporanox, Janssen ; . The azole antifungals inhibit the synthesis of ergosterol, the principal sterol in fungal membranes. Amphotericin B belongs to the class of polyene antifungals, which binds to ergosterol, resulting in increased membrane leakage of cellular components. The lack of clinical data with aminofungin does not allow for comparisons with other echinocandins, although there is little reason to believe aminofungin would be more or less efficacious or less tolerable than the others. In general, the echinocandins exhibit similar or better efficacy than other antifungals, yet none of the other antifungals exhibit the same broad spectrum of activity without adverse effects. For instance, amphotericin B is still considered a first-line antifungal and has a broad spectrum of activity, but it has considerable renal toxicity associated with its use, resulting in higher mortality rates and higher cost of treatment. There have also been significant infusion-related toxicities fever, chills, rigors, myalgias, arthralgias, etc. ; associated with its use. The azole antifungals are less toxic than amphotericin B, yet also have a narrower spectrum of activity and resistance is becoming an issue with their use. Thus, echinocandins have the potential to dominate the antifungal market; the market share of aminofungin specifically would depend on its clinical performance relative to the other echinocandins.
Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children' s Hospital Medical Center, Cincinnati OH, USA Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands Received 4 July 2001; accepted 26 September 2001.
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Researcher: patricia berg, phd, associate professor, department of biochemistry and molecular biology, george washington university medical center, washington, dc.
Success has many fathers, but failure is an orphan, " goes the old saying. But that maxim doesn't hold true when it comes to breakthrough prescription drugs, at least as far as the media are concerned. Fifty-three percent of the stories in the study treated prescription drugs in a favorable light, but even then it was rare that the networks mentioned the name of the drug companies producing them. Only 17 of the 70 favorably-slanted stories 24 percent ; named the company responsible for drugs held up as "promising" or a "breakthrough." Although private pharmaceutical firms are essential to medical breakthroughs, a full 80 and parlodel.
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PROJECTIONS OF THE INCIDENCE AND PREVALENCE OF PATIENTS ON RENAL REPLACEMENT THERAPY FROM UNTIL THE YEAR 2010. Y.NA1, L. TRPESKI1, J KAPPEL2, S. FENTON.3 1CANADIAN ORGAN REPLACEMENT REGISTER, CANADIAN INSTITUTE FOR HEALTH INFORMATION, 2UNIVERSITIES OF SASKATCHEWAN AND 3TORONTO and pioglitazone.
The YRBS and Add Health data-sets are among the few available that ask young people about substance use, sexual activity, condom use, and the link between substance use and sex. Because they are both school-based samples, students who were absent or who dropped-out were not included. As these students represent some of the most at-risk teens, findings from these analyses should be viewed critically and may not be generalizable to all adolescents. Additionally, social desirability and confidentiality concerns may prevent adolescents from truthfully disclosing their actual levels of substance use and risky sexual activity. For discussion of sample characteristics, methodology, and variable and measurement descriptions, see Appendix D. 2 CASA analysis of data from the 1997 Youth Risk Behavior Survey. 3 CASA analysis of data from the 1997 Youth Risk Behavior Survey. 4 Henry J. Kaiser Family Foundation & YM Magazine. 1999 ; . 1998 National Survey of Teens: Teens talk about dating, intimacy, and their sexual experiences. Menlo Park, CA: Kaiser Family Foundation. 5 Schuster, M. A., Bell, R. M., & Kanouse, D. E. 1996 ; . The sexual practices of adolescent virgins: Genital sexual activities of high school students who have never had sex. American Journal of Public Health, 86 11 ; , 1570-1576. 6 CASA analysis of data from the 1997 Youth Risk Behavior Survey. 7 Of these, eight percent used marijuana alone and four percent used both marijuana and cocaine; virtually no students used cocaine without also using marijuana during this time period. CASA analysis of data from the 1997 Youth Risk Behavior Survey. 8 Johnston, L.D., O'Malley, P.M. & Bachman, J.G. 1998 ; . The monitoring the future study, 1975-1998, Volume I, secondary school students. U.S. Department of Health and Human Services, National Institute on Drug Abuse 9 CASA analysis of data from the 1997 Youth Risk Behavior Survey. 10 Ode, K. 1999 ; . A date-rape victory, but let's keep a clear head: Most dangerous and widely used drug alcohol is still available everywhere. Star Tribune, 2E, January 30. 11 Multiple regression analysis was conducted to examine the association between substance use and adolescent sexual risk behaviors. Eighteen models were constructed in all, one for each independent substance use variable Ever drank; Drank on 10 + days in lifetime; Drank 5 + drinks on one occasion in past 30 days; Ever used drugs; Used drugs 20 + times in lifetime; Used marijuana or cocaine 10 + times in past 30 days ; on each dependent sexual activity variable Ever had sexual intercourse; Have had sexual intercourse with 4 + partners in lifetime; Used a condom at last sexual intercourse ; . Each model controlled for the independent impact of gender, race, age and parents' educational level. See Appendix E. 12 CASA analysis of data from the 1997 Youth Risk Behavior Survey. 13 A third of the Add Health sample are 14 or younger, compared to 10 percent of the YRBS sample. According to our analysis of the Add Health data, the substance-use sexual activity odds ratios for 15 16 year olds were 1.9 for alcohol users and 4.3 for drug users. For teens 17 and older, 1.7 for alcohol users and 4.0 for drug users. CASA analysis of data from the 1995 Add Health Survey. 14 Brooks-Gunn, J., & Furstenberg, F.F. Jr. 1989 ; . Adolescent sexual behavior. American Psychologist, 44 2 ; , 249257. 15 Cooper, M. L., Peirce, R. S., & Huselid, R. F. 1994 ; . Substance use and sexual risk taking among black and white adolescents. Health Psychology, 13, 251-262; Leigh, B. C., Schafer, J., & Temple, M. T. 1995 ; . Alcohol use and contraception in first sexual experiences. Journal of Behavioral Medicine, 18 1 ; , 81-95. 16 Schuster, M. A., Bell, R. M., & Kanouse, D. E. 1996 ; . The sexual practices of adolescent virgins: Genital sexual activities of high school students who have never had sex. American Journal of Public Health, 86 11 ; , 1570-1576. 17 Elliott, D. S., & Morse, B. J. 1989 ; . Delinquency and drug use as risk factors in teenage sexual activity. Youth & Society, 21, 32-60. 18 Lowry, R., Hotlzman, D., Truman, B. I., Kahn, L., Collins, J. L., & Kolbe, L. J. 1994 ; . Substance use and HIVrelated risk behaviors among U.S. high school students: Are they related? American Journal of Public Health, 84 7 ; , 1116-1120; Doljanac, R. F., & Zimmerman, M. A. 1998 ; . Psychosocial factors and high-risk sexual behavior: Race differences among urban adolescents. Journal of Behavioral Medicine, 21 5 ; , 451-467; Strunin, L., & Hingson, R. 1992 ; . Alcohol, drugs, and adolescent sexual behavior. International Journal of the Addictions, 27 2 ; , 129-146; Chassin, L., & DeLucia, C. 1996 ; . Drinking during adolescence. Alcohol Health & Research World, 20 3 ; , 175178; Shrier, L. A., Emans, S. J., Woods, E. R., & DuRant, R. H. 1996 ; . The association of sexual risk behaviors and, for example, does nlzoral work.
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Results: The most disabling event in the medical history of these patients was the presence of a CSF shunt for the treatment of hydrocephalus. The two patients that needed more than three shunt revisions, mostly for septic complications, were those with evident neurological sequelae. The difference between QOL of patients with or without a CSF shunt was statistically significant. Conclusions: Although operated upon when neurosurgical tools were less sophisticated than today, more than 80% of the patients have a completely "normal" life when matched with control groups for age and sex in the normal population.
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1. What is the overarching goal? Return to independent living in the community with no alcohol dependency. 2. Patient's problems : See Plan of Care Attachment. 3. What is the impact of each problem on the patient's health and quality of life? Key is to focus on ETOH depression as overriding problem and the effects that this has on quality of life for elders. Impact is physical, psychological, social, spiritual. 4. What strengths and resources does the patient have for addressing each problem? Patient's education, intelligence, physical strength, family support system, eligibility for MA. 5. What additional information is needed?.
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Analgesics may also be used, but under controlled conditions to prevent the development of overuse and consequent withdrawal symptoms.15 Certain groups of patients should either not receive triptans, or be prescribed them with caution. Triptans are contraindicated for patients with evidence of existing cardiovascular disease, uncontrolled hypertension, severe renal and hepatic impairment, and for those receiving other triptans, ergotamine and its derivatives and monoamine oxidase inhibitors MAOIs ; . Eletriptan is specifically contraindicated for patients concomitantly using selective serotonin reuptake inhibitors SSRIs ; . Caution should be used when prescribing triptans to patients with risk factors for cardiovascular disease, e.g. history of smoking or men aged 40 years ; , controlled hypertension, any renal or hepatic disease, hypersensitivity reactions and pregnant or breast-feeding women.47, 48 Patients with the rare migraine variants should also not be prescribed triptans. Drugs without good evidence of utility include paracetamol monotherapy due to lack of efficacy ; , and opiates and barbiturates due to safety concerns ; .15 Oral ergotamine has limited efficacy due to poor bioavailability, and is associated with a range of potentially severe side effects ergotism ; .49 Parenteral formulations of ergotamine and dihydroergotamine DHE ; are more effective, 49 but are not available in the UK. Table 6. Summary of the clinical profiles of the different triptan drugs from randomised, placebocontrolled clinical trials.21, 44.
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Guidelines. Fortunately, there is an ongoing dialogue between the medical community and the Centers for Medicare and Medicaid Services CMS ; that provides a forum for changes consistent with current medical knowledge and terminology. Requests by the American Association of Clinical Endocrinologists beginning December 2002 to the National Center for Vital Statistics CDC ; ICD-9 committee, which maintains the U.S. classification system, resulted in CMS adopting new codes for glucose abnormalities. Effective October 1, 2003, the new codes offer separate diagnoses for the various manifestations of glucose abnormalities. As published in the Federal Register in July 2003.
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A monthly publication by The Pharmacy Guild of Australia NT Branch ; and the Top End Division of General Practice, aimed at keeping all NT Pharmacists in-the-loop and up-to-date. From the NT Guild Branch.
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28 patients who had arrhythmias unrelated to digitalis were helped by DPH. In three patients the relationship of the abnormal rhythm to digitalis was unclear, and one of these had a favorable response to DPH. Both supraventricular and ventricular arrhythmias induced by digitalis appeared ~usceptibleto the action of DPH. I n general, the response was rapid, frequently occurring during the infusion period, but on several occasions no result was seen until after the total dose was given. In one instance there was no response until six minutes after cessation of the injection. Although almost half the patients had arteriosclerotic heart disease, reflecting the patient population in a large municipal hospital, etiology of cardiac disease a p peared to play litde role in the response to DPH, except in patients who had multiple pulmonary emboli with cor pulmonale Table 4 ; . Five patients had either atrial flutter or fibrillation. None of these responded with si, pificant slowing of ventricular response or convenion of rhythm, even though one of these arrhythmias was felt to be the result of excess digitalis. This finding is in accord with the experience of Conn."' T y p ical responsg to DPH are illustrated In Fig. 1. Three of the patients with nondigitalis induced arrhythmias who responded to D P merit further comment. T h e first was a 51-year-old man with severe aortic incompetence who experienced five consecutive bouts of ventricular tachycardia over a period of several weeks without evidence of myocardial infarction, all of which responded readily to intravenous DPH. Two subsequent episodes of the same arrhythmia were not corrected by D P and subsided spontaneously. The patient expired shortly after cardiopulmonary bypass for insertion of a n aortic valve pmsthesic. The other two patients with nondigitalis induced disorders had paroxysmal arrhythmias, one an atrial and the second a nodal tachycardia. T h e first was a 62.
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