PDAs and hand-helds: world without wires.
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Computer Communication Networks↗
Biomedical subjects
S Noble
Publications and source records attributed to S Noble.
One woman's tragedy.
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Drug Therapy, Computer-Assisted↗
Mammalian reovirus L3 gene sequences and evidence for a distinct amino-terminal region of the lambda1 protein.
To complement evidence for nucleoside triphosphate phosphohydrolase (NTPase), RNA helicase, RNA 5' triphosphate phosphohydrolase, and nucleic acid-binding activities by the core shell protein lambda1 of mammalian orthoreoviruses (reoviruses), we determined nucleotide sequences of the lambda1-encoding L3 gene segments from three isolates: type 1 Lang (T1L), type 2 Jones (T2J), and type 3 Dearing (T3D). The T1L and T3D L3 gene sequences and deduced lambda1 protein sequences shared high levels of identity (97.7% and 99.3%, respectively). The lambda1 sequences differed at only 9 of 1275 amino acids. Two single-nucleotide insertions relative to a previously published sequence for T3D L3 extended the lambda1 open reading frame to within 60 nucleotides of the plus-strand 3' end for T3D and the other isolates sequenced, in keeping with the short 3' nontranslated regions of the other nine gene segments. Seven of the nine amino acid differences between T1L and T3D lambda1 were located within the amino-terminal 500 residues of lambda1, a region with putative sequence similarities to NTPases and RNA helicases. The T2J L3 and lambda1 sequences were found to be more divergent, especially within the amino-terminal 180 residues of lambda1, preceding the putative CCHH zinc finger motif. The T2J L3 sequence, along with partial sequences for L3 genes from three other reovirus isolates, suggested that one or more of the polymorphisms at amino acids 71, 215, 500, 1011, and/or 1100 in lambda1 contribute to the L3-determined differences in ATPase activities by T1L and T3D cores. The findings contribute to our ongoing efforts to elucidate sequence-structure-function relationships for the lambda1 core protein.
Adenosine Triphosphatases↗
Clodronate: a review of its use in breast cancer.
UNLABELLED: Like other members of its class, the bisphosphonate clodronate (clodronic acid) inhibits bone resorption. The efficacy of oral clodronate 1600 mg/day in reducing the incidence of skeletal complications and metastasis development has been assessed in several clinical trials in patients with breast cancer. Long term use of oral clodronate significantly reduced the total cumulative incidence of skeletal events (including fractures, hypercalcaemia, and the need for radiotherapy for bone pain) compared with that in placebo recipients in 2 randomised double-blind placebo-controlled studies, each involving >100 patients. Significant differences in favour of clodronate were also seen in the frequency of some individual skeletal events in 1 trial. A nonblind trial in 302 patients considered to be at high risk of developing metastases found that, at a 3-year follow-up, significantly fewer patients who received clodronate for 2 years developed skeletal metastases than those in a control group. Clodronate recipients were also significantly less likely than controls to develop visceral metastases, and had significantly higher survival rates. A smaller double-blind placebo-controlled study in women with recurrent breast cancer found that clodronate significantly decreased the total number of new skeletal metastases, but not the number of patients who developed them. In a nonblind trial in 299 patients with node-positive breast cancer, however, the incidence of skeletal metastases did not differ significantly between patients who received clodronate for 3 years and those in a control group. In addition, clodronate recipients had a significantly greater incidence of nonskeletal metastases (local and visceral), and significantly lower survival rates. Intravenous or oral clodronate has been well tolerated in clinical trials. The most common adverse effects reported were mild gastrointestinal disturbances such as nausea, vomiting and diarrhoea. All these events were transient, and usually resolved without stopping treatment. CONCLUSIONS: Clodronate is a well tolerated bisphosphonate, available in both oral and intravenous forms, that significantly reduces the incidence of skeletal complications associated with breast cancer. Further research is needed to establish more clearly its efficacy in reducing metastasis development, to assess its efficacy compared with other bisphosphonates, and to determine which patients will benefit most from treatment. Currently, clodronate is probably most effective in the treatment and prevention of general skeletal complications in patients with breast cancer.
Bone Resorption↗
Aprotinin: an update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery.
UNLABELLED: Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transfusions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority during surgery because of shortages of donor blood, the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue which acts in a number of interrelated ways to provide an antifibrinolytic effect, inhibit contact activation, reduce platelet dysfunction and attenuate the inflammatory response to CPB. It is used to reduce blood loss and transfusion requirements in patients with a risk of haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent with tranexamic acid: high dose aprotinin either reduces blood loss significantly more than, or to an equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage regimens consistently result in similar reductions in blood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerated, and the adverse events seen are those expected in patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in <0.1 to 0.6% of patients receiving aprotinin for the first time. The results of original reports indicating that aprotinin therapy may increase myocardial infarction rates or mortality have not been supported by more recent studies specifically designed to investigate this outcome. However, a tendency to early vein graft occlusion with aprotinin has been shown and care with anticoagulation and vessel grafts is required. No comparative tolerability data between aprotinin and the lysine analogues, aminocaproic acid and tranexamic acid, are available. CONCLUSION: Comparative tolerability and cost-effectiveness data for aprotinin and the lysine analogues are required to more fully assess their individual roles in reducing blood loss and transfusion requirements in patients undergoing CPB during OHS and/or CABG. However, clinical evidence to date supports the use of aprotinin over its competitors in patients at high risk of haemorrhage, in those for whom transfusion is unavailable or in patients who refuse allogenic transfusions.
Aprotinin↗
Isosorbide 5-mononitrate: a review of a sustained-release formulation (Imdur) in stable angina pectoris.
UNLABELLED: Imdur (IMD) is a sustained-release isosorbide 5-mononitrate preparation for the treatment of chronic stable angina pectoris. Controlled medication release is achieved using the Durules principle of insoluble matrix embedding. Data from randomised double-blind trials show that IMD 60 mg once daily (the most widely studied dosage) has significant antianginal and anti-ischaemic effects compared with placebo after 2 weeks' treatment. Efficacy was generally observed approximately 1 to 12 hours after administration, indicating that once-daily administration in the morning will provide effective prophylaxis of symptoms throughout the day. Improvements from baseline are generally maintained during IMD repeated treatment. There was no evidence of classical tolerance to IMD 30 to 240 mg/day in a large well designed study. Although improvements from baseline were maintained over 6 weeks with IMD 30 or 60 mg/day, statistical significance versus placebo was eventually lost because of improved performance in the placebo group. IMD 120 or 240 mg/day were more effective than placebo after 6 weeks. Studies lasting up to 2 weeks found no evidence of tolerance to IMD 60 mg/day. In comparative trials lasting approximately 2 weeks, IMD 60 mg once daily was more effective than isosorbide dinitrate 30 mg 4 times daily and similar to or better than isosorbide dinitrate 20 mg 3 times daily. Preliminary data show that IMD 60 mg once daily has similar efficacy to diltiazem 60 mg 3 times daily and is at least as effective as certain other sustained-release isosorbide 5-mononitrate preparations. There is no evidence for rebound worsening of ischaemia 24 hours after IMD administration. Abrupt discontinuation during long term IMD treatment may exacerbate anginal symptoms. In general, IMD is well tolerated. The most frequently reported adverse event, headache, is usually mild to moderate, improves with long term therapy and rarely leads to treatment withdrawal. Patient compliance is better with once-daily administration of IMD than with twice-daily administration of conventional isosorbide 5-mononitrate. CONCLUSIONS: In patients with chronic stable angina, IMD provides effective antianginal prophylaxis for up to 12 hours and does not seem to be associated with rebound phenomena at the end of the dosage interval. Improvements from baseline are maintained during repeated administration, although loss of statistically significant superiority over placebo was evident during 6 weeks' treatment with IMD < or =60 mg/day in 1 study. Further evaluation of comparative efficacy (particularly with respect to other sustained-release preparations) and long term effects would be beneficial. Nevertheless, the available data suggest that IMD is a useful and convenient agent for the treatment of patients with chronic stable angina pectoris.
Adrenergic beta-Antagonists↗
Eptifibatide: a review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention.
UNLABELLED: Eptifibatide, a cyclic peptide, is a highly specific, intravenously administered glycoprotein (GP) IIb/IIIa receptor antagonist. By preventing fibrinogen binding to the GP IIb/IIIa receptor, eptifibatide inhibits platelet aggregation and prevents thrombus formation. Clinically, the drug is used as an adjunct to heparin and aspirin. The PURSUIT trial, conducted in >10,000 patients with unstable angina or non-Q-wave myocardial infarction (MI), showed that eptifibatide (180 microg/kg bolus then 2 microg/kg/min infusion for < or =72 hours) reduces the 30-day risk of death or nonfatal MI, with this benefit apparent at 96 hours. The absolute reduction in this end-point of 1.5% persisted at 6 months. The drug is effective in patients undergoing percutaneous coronary intervention (PCI), and, as shown in the North American subgroup, in patients in whom medical management is appropriate. Eptifibatide is also beneficial in patients undergoing PCI, whether or not they have unstable angina or non-Q-wave MI. In a dosage of 135 microg/kg then 0.5 microg/kg/min for 24 hours, eptifibatide reduced the 30-day risk of a combined end-point (death, nonfatal MI and urgent or emergency coronary interventions) by 2.5% (absolute reduction) in patients undergoing PCI in the IMPACT-II trial, when measured by per-protocol (patients treated), but not intent-to-treat, analysis. The drug also decreased the incidence of abrupt vessel closure and ischaemic cardiovascular complications in the first 24 hours (the period of greatest risk). Bleeding episodes are the most common adverse event associated with eptifibatide therapy. Although the incidence of major bleeding is increased with eptifibatide, most bleeding episodes are minor and occur at the vascular access site. The drug is not associated with an excess of intracranial bleeds, stroke or thrombocytopenia, does not appear to increase bleeding risk in patients undergoing coronary artery bypass graft (CABG), and does not cause antibody formation. Limited data suggest that eptifibatide may improve coronary flow when combined with alteplase in patients with acute Q-wave MI, but the possibility of increased bleeding with eptifibatide plus thrombolytics should be borne in mind. CONCLUSIONS: Intravenous eptifibatide, when combined with aspirin and heparin, reduces the 30-day risk of ischaemic events in patients with unstable angina and non-Q-wave MI and decreases ischaemic cardiovascular complications at the time of greatest risk in patients undergoing PCI. With its acceptable tolerability profile eptifibatide is a suitable option as a short term adjunct in these clinical settings. Whether eptifibatide in combination with fibrolysis may improve outcome in patients with acute Q-wave MI has yet to be determined.
Angina, Unstable↗
Bivalent cholera and typhoid vaccine.
The live attenuated vaccine strains Vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a can be combined into an oral bivalent vaccine without compromising the immunogenicity of the individual vaccine strains. Seroconversion rates of 87 to 94% for Inaba vibriocidal antibodies and 72 to 91% for anti-S. typhi lipopolysaccharide antibodies (IgG or IgA) were reported in healthy European volunteers receiving a bivalent CVD 103-HgR/Ty21a vaccine-based schedule (bivalent vaccine on day 1 and monovalent Ty21a vaccine on days 3 and 5). The immunogenicity of bivalent CVD 103-HgR/Ty21a vaccine is not adversely affected by concomitant administration of mefloquine, yellow fever vaccine or oral polio vaccine. Chloroquine may reduce the immunogenicity of the CVD 103-HgR component and proguanil may reduce the immunogenicity of the Ty21a component. Bivalent CVD 103-HgR/Ty21a vaccine does not adversely affect the immunogenicity of the yellow fever YF 17D vaccine. The type, incidence and severity of adverse events seen in individuals receiving bivalent CVD 103-HgR/Ty21a vaccine-based schedules are similar to those that occur with the monovalent vaccines.
Bacterial Vaccines↗
Cidofovir: a review of its use in cytomegalovirus retinitis in patients with AIDS.
UNLABELLED: Cidofovir is an antiviral nucleotide analogue with significant activity against cytomegalovirus (CMV) and other herpesviruses. The drug is indicated for the treatment of CMV retinitis, a sight-threatening condition, in patients with AIDS. Cidofovir has a long intracellular half-life which allows for a prolonged interval (2 weeks) between maintenance doses. In contrast, other intravenous treatment options for patients with CMV retinitis (i.e. ganciclovir and foscarnet) must be administered on a daily basis. The efficacy of intravenous cidofovir has been demonstrated in patients with AIDS and previously untreated CMV retinitis in multicentre randomised trials, and in a dose-finding study of cidofovir in patients with AIDS and previously treated relapsing CMV retinitis. Clinical trials have been relatively small (n < or = 100 patients) and no studies have been conducted directly comparing intravenous cidofovir with the more established intravenous agents, ganciclovir or foscarnet. Indirect comparisons of clinical trial data suggest that intravenous cidofovir may have similar efficacy to intravenous ganciclovir or foscarnet in delaying progression of CMV retinitis. However, such comparisons must be made with caution because of potential differences in patient populations, data analysis techniques and interobserver variability in the masked assessment of retinal photographs. Nevertheless, intravenous cidofovir offers a less intrusive administration regimen than intravenous ganciclovir or foscarnet because of its prolonged dosage interval. Since therapy is life-long, patients receiving daily intravenous ganciclovir or foscarnet (but not cidofovir) usually require an indwelling central venous catheter and are therefore at increased risk of serious infection. The relatively long dosage interval for cidofovir may also have favourable implications in terms of overall treatment costs and patient quality of life, although specific data are very limited. Potentially irreversible nephrotoxicity is the major treatment-limiting adverse event associated with intravenous cidofovir in patients with AIDS-related CMV retinitis. Anterior uveitis/iritis has been reported frequently with intravenous cidofovir in postmarketing reports and a small number of patients have developed hypotony. Other treatment options for CMV retinitis are also associated with serious adverse events, and selection of pharmacotherapy will depend on a number of factors including retinitis lesion characteristics, patient quality-of-life issues and efficacy and tolerability profiles of available therapies. CONCLUSION: Although the extent of its use may be limited by its adverse event profile, cidofovir offers a useful addition to the limited number of drugs available for the treatment of CMV retinitis in patients with AIDS.
AIDS-Related Opportunistic Infections↗
Adefovir dipivoxil.
Adefovir dipivoxil is an ester prodrug of the nucleoside reverse transcriptase inhibitor adefovir (PMEA), the prototype compound of the acyclic nucleoside phosphonates. It has better oral bioavailability than the parent compound. Adefovir dipivoxil 120mg once daily significantly reduced viral load compared with placebo when added to standard antiretroviral therapy in a 6-month, double-blind study in patients with HIV infection. Viral suppression was maintained during an additional 6-month nonblind extension phase. The drug was most effective in patients with baseline isolates containing the M184V lamivudine resistance mutation according to data from a virological substudy of a large placebo-controlled trial. Adefovir dipivoxil 60mg was as effective as 120mg (both once daily) after 20 weeks' treatment in a randomised double-blind study in antiretroviral-experienced (protease inhibitor-naive) patients. Viral suppression was generally maintained in patients who developed new reverse transcriptase mutations during adefovir dipivoxil monotherapy or combination therapy for up to 12 months. No clear pattern of particular clinical resistance mutations has emerged. GI disturbances, hepatic effects and delayed renal abnormalities are the principal adverse events seen with adefovir dipivoxil. Reductions in serum free carnitine levels may occur and coadministration of L-carnitine is recommended.
Adenine↗
Oseltamivir.
Oseltamivir is the oral prodrug of GS4071, a selective inhibitor of influenza A and B viral neuraminidase. After absorption from the gastrointestinal tract oseltamivir is efficiently converted to GS4071, which is maintained at high and sustained concentrations in plasma. Based on studies in rats and ferrets, GS4071 appears to be effectively distributed to all tissues, including major sites of infection in the upper and lower respiratory tracts. Oral oseltamivir was an effective treatment in naturally occurring influenza when administered within 36 hours of symptom onset, reducing both the duration and severity of symptoms and the incidence of secondary complications in influenza-infected patients enrolled in 2 large placebo-controlled, double-blind trials. Prophylactic oral administration of oseltamivir was effective in reducing the incidence of influenza illness according to pooled data from 2 large placebo-controlled, double-blind trials of healthy nonimmunised volunteers during periods of seasonal influenza activity. The reported incidence of viral resistance to GS4071 was low in clinical isolates from oseltamivir treatment studies. All known GS4071 resistant genotypes are growth disadvantaged and display significantly reduced infectivity in animals. Oseltamivir was well tolerated in human volunteers and patients in clinical trials. Treatment-related adverse events (primarily gastrointestinal) were mild and transient in nature.
Acetamides↗
Stavudine: an update of its use in the treatment of HIV infection.
UNLABELLED: Stavudine is a thymidine nucleoside analogue which is phosphorylated intracellularly to an active metabolite, stavudine 5'-triphosphate. This metabolite inhibits HIV replication, either by competing with thymidine 5'-triphosphate for incorporation into viral DNA by reverse transcriptase or by causing premature termination of the viral chain after incorporation. Resistance to stavudine, either alone or as part of resistance to multiple nucleoside reverse transcriptase inhibitors, has been reported; however, high-level resistance is uncommon even after long periods of treatment. Initial treatment with stavudine-containing triple therapies reduced HIV RNA levels to below the limit of detection (LOD; 500 copies/ml) in 68 to 100% of antiretroviral-naive patients after at least 20 weeks of treatment. Effects on clinical outcomes have not yet been established, although earlier trials showed significant improvements with stavudine (alone or with 1 other drug) in patients who had previously received zidovudine. Results from 2 randomised nonblind clinical trials indicated that the efficacy of stavudine-containing triple therapy was similar to that of zidovudine-containing triple therapy (when used in combination with the same drugs), although there were no statistical comparisons. Improvements in surrogate end-points have also been seen in trials in antiretroviral-experienced patients receiving stavudine and 2 or 3 other antiretroviral agents. Stavudine-containing combination therapies have also been effective in reducing viral load and increasing CD4+ lymphocyte count in children, although data are limited. Like other nucleoside analogues, stavudine treatment can cause mitochondrial toxicity. The major adverse effect from this observed with stavudine therapy is peripheral neuropathy, which is both dosage- and treatment duration-dependent. Most cases respond to short term cessation of treatment and reintroduction of stavudine at half the previous dosage. CONCLUSION: Stavudine-containing triple therapies are effective in the treatment of antiretroviral-naive adults with HIV infection as assessed by surrogate end-points; earlier trials involving 1 or 2-drug therapy showed that stavudine can significantly improve clinical end-points. Stavudine has also been beneficial as part of combination regimens in antiretroviral-experienced patients and children with HIV infection, although data are limited and more studies are needed. High-level resistance to stavudine is uncommon. The major adverse event associated with treatment is peripheral neuropathy, which may limit its use in some patients. Currently, stavudine has a valuable role as part of initial triple therapy in antiretroviral-naive adults with HIV/AIDS.
Anti-HIV Agents↗
Didanosine: an updated review of its use in HIV infection.
UNLABELLED: Didanosine, like zidovudine, stavudine and lamivudine, is a nucleoside analogue reverse transcriptase inhibitor (NRTI). In the target cell for HIV, didanosine is converted to its active moiety, dideoxyadenosine-5'-triphosphate (ddATP), which inhibits HIV reverse transcriptase and terminates viral DNA growth. It is now well established that didanosine therapy produces beneficial effects on virological and immunological markers of HIV disease and improves clinical outcome in adults or children with HIV infection. In numerous clinical trials, pronounced and sustained decreases in plasma HIV RNA levels and increases in CD4+ cell counts occurred in previously untreated or antiretroviral therapy-experienced patients treated with didanosine in combination with at least 1 other antiretroviral drug; zidovudine, stavudine, lamivudine, nevirapine, nelfinavir and hydroxyurea (hydroxycarbamide) are among the drugs that have been given in combination with didanosine. Of note, HIV RNA levels decreased to below the limits of detection in some patients receiving triple or dual therapy with didanosine-containing regimens. In double-blind, placebo-controlled trials, triple therapy with didanosine, zidovudine and nevirapine was significantly more effective than dual therapy with various combinations of these agents in improving surrogate disease markers in treatment-naive patients and in delaying disease progression or death in treatment-experienced patients with advanced disease. Improvements in virological and immunological markers were greater with didanosine-containing triple regimens than with dual therapy or monotherapy in comparative trials. Triple therapy with didanosine, stavudine and indinavir showed efficacy similar to that of various other triple therapy regimens in nonblind comparative trials. Comparator regimens included combinations of stavudine, lamivudine plus indinavir, zidovudine, lamivudine plus indinavir and didanosine, stavudine and nevirapine. Combination therapy with didanosine plus hydroxyurea as dual therapy or with a third agent produced marked and sustained decreases in HIV RNA levels in the plasma and in lymph nodes. Combination therapy with didanosine and zidovudine delays disease progression and prolongs survival in patients with intermediate or advanced HIV infection. In large, randomised, double-blind, clinical trials, dual therapy with didanosine plus zidovudine was significantly more effective than zidovudine monotherapy in preventing disease progression and prolonging survival in previously untreated or antiretroviral therapy-experienced patients with intermediate or advanced HIV infection. Pancreatitis and peripheral neuropathy are serious adverse effects of didanosine. These effects are dose-related and usually reversible after discontinuation of treatment. Nausea, vomiting, diarrhoea and/or abdominal pain have been reported in patients receiving treatment with the drug. CONCLUSIONS: Didanosine is an effective and generally well tolerated drug in previously untreated and antiretroviral therapy-experienced patients with HIV infection. Given once or twice daily, it has an important role as a component of triple combination regimens for the treatment of patients with symptomatic or asymptomatic HIV infection.
Adult↗
Indinavir: a review of its use in the management of HIV infection.
Indinavir is a protease inhibitor used in the treatment of patients with HIV infection. Combination antiretroviral therapy with indinavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is associated with greater reductions in viral load, greater increases in CD4+ cell counts, and reduced morbidity and mortality when compared with 2 NRTIs alone. In the landmark clinical trial ACTG 320, the rate of progression to AIDS or death (primary end-point) among zidovudine-experienced patients treated with indinavir, zidovudine and lamivudine was approximately half that of patients who received only zidovudine plus lamivudine (6 vs 11%; p < 0.001). The durability of an indinavir-containing regimen was demonstrated in Merck protocol 035, an ongoing trial in which a significant proportion of patients had sustained viral suppression for up to 3 years. Merck protocol 039, also an ongoing trial, showed a greater effect on surrogate markers of HIV disease progression with indinavir-based triple therapy than with zidovudine plus lamivudine or indinavir monotherapy in patients with advanced disease (median baseline CD4+ count 15 cells/microL). Numerous additional clinical trials have established the beneficial antiviral and immunological effects of indinavir in both antiretroviral-naive and -experienced patients with HIV infection. Indinavir is associated with various drug class-related adverse events, including gastrointestinal disturbances (e.g. nausea, diarrhoea), headache and asthenia/fatigue. A lipodystrophy syndrome has been commonly reported with indinavir and other protease inhibitors combined with NRTIs, but it has also been reported in many protease inhibitor-naive patients, and a definitive causal link has not been established between the syndrome and protease inhibitors. Nephrolithiasis may develop in about 9% of patients receiving indinavir but does not appear to be associated with other protease inhibitors; <0.5% of patients receiving indinavir discontinue the drug because of nephrolithiasis, which may be the extreme end of a continuum of crystal-related renal syndromes. Additional renal problems (e.g. nephropathy) have been reported in small numbers of patients receiving indinavir. In summary, indinavir is a protease inhibitor with well documented efficacy when used as part of combined therapy in patients with HIV infection. Both US and UK treatment guidelines continue to recommend protease inhibitor-based regimens including indinavir as a first-line option. Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues. Indinavir-containing triple therapy has demonstrated positive effects not only on surrogate markers of disease progression, but also on clinical end-points of mortality and morbidity in patients with HIV disease. Protease inhibitors are a significant advance in the care of patients with HIV infection, and, in an era of evidence-based medicine, indinavir represents an important component of antiretroviral treatment strategies.
Animals↗
Vinorelbine in advanced non-small cell lung cancer. A pharmacoeconomic review.
UNLABELLED: Vinorelbine is a semisynthetic vinca alkaloid that is effective against advanced non-small cell lung cancer (NSCLC). Myelosuppression is the primary dose-limiting toxicity; vinorelbine is otherwise relatively well tolerated. Two studies assessed the cost effectiveness of vinorelbine with or without cisplatin based primarily on data from a phase III comparison with vindesine plus cisplatin. Survival and cost data from this study were supplemented with those from other sources. One model simulated total management costs for the 4986 patients diagnosed with stage IV NSCLC in Canada in 1992. The other applied US cost data to the outcomes from the phase III trial. Using vinorelbine monotherapy or vinorelbine plus cisplatin produced a survival benefit and net cost savings compared with best supportive care according to the Canadian model (and preliminary data from a third analysis, conducted in the US). In the Canadian analysis, incremental cost effectiveness for inpatient or outpatient vinorelbine plus cisplatin ranged from 7450 Canadian dollars ($Can) to $Can30,770 (1993 values) per year of life saved (YLS) compared with outpatient cisplatin plus either etoposide or vinblastine. Cost-effectiveness ratios for vinorelbine plus cisplatin in the US analysis (1994 values) were $US18,000 (vs cisplatin plus etoposide) and $US15,500 (vs cisplatin plus vindesine) per YLS [all inpatient administration]. Detailed pharmacoeconomic comparisons with other current standard regimens (e.g. paclitaxel plus either cisplatin or carboplatin) are not available. Sensitivity analyses suggest that the cost effectiveness of vinorelbine-based therapy is robust to changes in assumptions regarding efficacy and the cost of managing toxicity. Limitations of the available pharmacoeconomic data include the retrospective nature of the analyses, inclusion of data from sources other than the main phase III trial (e.g. those for best supportive care and some chemotherapy regimens), and exclusion of some costs for hospitalisation and/or management of toxicity. CONCLUSIONS: Although some limitations apply, the available data suggest that vinorelbine alone or in combination with cisplatin is cost saving compared with best supportive care for NSCLC, and that vinorelbine plus cisplatin is cost effective compared with some other combination regimens. The pharmacoeconomic placing of vinorelbine in relation to a number of other currently recommended first-line treatments for NSCLC has yet to be resolved, and data from ongoing multicentre phase III trials are awaited with interest. In the meantime, vinorelbine-based chemotherapy appears to be a suitable choice for first-line treatment of advanced NSCLC from both clinical and pharmacoeconomic perspectives.
Antineoplastic Agents, Phytogenic↗
Zero tolerance for billing errors.
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Abstracting and Indexing↗
Kids under the weather: a rainbow of care for sick children.
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Child↗
Successful steps to enterprisewide integration.
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Hospital Information Systems↗