Drugs
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Review
Current drug treatment options in neonatal hyperbilirubinaemia and the prevention of kernicterus.
Neonatal jaundice is a frequent problem in neonatology, but the advent of phototherapy which has simplified its treatment, it no longer represents a major concern. Early hospital discharge of neonates has now resulted in a re-emergence of kernicterus. Neonatal jaundice is principally the result of a transient deficiency of bilirubin conjugation, of a partial deficiency of hepatic bilirubin uptake and intracellular transport and of an increased enterohepatic circulation of the pigment. ⋯ In preterm infants the typical clinical feature of kernicterus is seen very rarely, and kernicterus is now a very infrequent postmortem observation. Since it is very difficult to distinguish the effects of bilirubin from other potentially toxic factors, it is difficult to give guidelines for the treatment of jaundice in very low birthweight infants other than to keep the serum bilirubin levels to a lower level than in full term infant (e.g. 10 mg/dl lower than in full term babies). The intramuscular administration of a single dose of Sn-mesoporphyrin (6 mumol/kg bodyweight) in healthy term or near-term infants seems to be a promising treatment modality for controlling hyperbilirubinaemia.
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Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. ⋯ This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.
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Ganciclovir is a nucleoside analogue which is used to treat and prevent cytomegalovirus (CMV) infection. Most recent clinical studies of ganciclovir in transplant recipients have focused on preventive approaches. When ganciclovir was last reviewed in Drugs in 1994, substantial data on post-transplantation CMV prophylaxis with this drug were available only for patients undergoing allogeneic bone marrow transplantation (BMT). Two strategies had emerged: prophylaxis for all patients or early treatment started after detection of asymptomatic CMV infection. Subsequently, a large double-blind study has shown that ganciclovir prophylaxis is more effective than early treatment in preventing early CMV disease after allogeneic BMT and is not associated with an increased incidence of neutropenia. However, mortality for the 2 strategies was similar. The efficacy of prophylactic intravenous ganciclovir in liver transplant recipients [including high risk donor seropositive/recipient seronegative (D+/R-) or antilymphocyte-treated patients] is now well established. Prophylaxis with oral ganciclovir was effective both overall and in D+/R-patients in a large placebo controlled study, and prolonged intravenous ganciclovir was significantly more effective than high dose aciclovir (acyclovir) in seropositive liver recipients. Early treatment with ganciclovir has proved useful in this setting. More limited data indicate that CMV prophylaxis with intravenous ganciclovir may be useful after heart or lung transplantation but its value in D+/-patients remains unclear. Combined chemoimmunotherapy may be valuable in these high risk patients but controlled data are lacking. Targeted prophylaxis with intravenous ganciclovir is effective in renal transplant recipients receiving antilymphocyte therapy; the role of oral ganciclovir in this setting is less clear. The value of ganciclovir in D+/- renal transplant recipients and its efficacy compared with high dose aciclovir have not been determined. ⋯ Ganciclovir is the only antiviral chemotherapy which reduces the risk of CMV infection or disease after most types of major transplantation. Unresolved issues include the best (and most cost-effective) use of ganciclovir and aciclovir after allogeneic BMT, the efficacy of oral ganciclovir compared with other anti-CMV regiments, the potential clinical effect of viral resistance during prolonged ganciclovir exposure and the value of ganciclovir in certain high risk transplant populations. In the meantime, ganciclovir has an important role in the prevention of CMV infection and disease after bone marrow and liver transplantation and is likely to gain wider clinical use in heart, lung and kidney transplant recipients.