Biomedical subjects

C M Perry

Publications and source records attributed to C M Perry.

At least 37 records · Page 2Linked to original sources

PubMed1999

Fomivirsen.

Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically inhibits replication of human cytomegalovirus. It achieves this by binding to complementary sequences on messenger RNA transcribed from the major immediate-early transcriptional unit of the virus. It is being developed for the treatment of cytomegalovirus retinitis. Mean maximum retinal concentrations of fomivirsen occurred approximately 2 days after a single intravitreal injection in monkeys. The elimination half-life of fomivirsen (after a single 115 microg dose) in monkey retina was 78 hours. Fomivirsen, administered as an intravitreal injection, significantly delayed progression of cytomegalovirus retinitis in patients with AIDS in preliminary clinical trials. In 18 patients with newly diagnosed, unilateral, peripheral cytomegalovirus retinitis treated with fomivirsen 165 microg once weekly for 3 weeks, then 165 microg every second week, the median time to disease progression was significantly longer than in 10 patients in whom fomivirsen treatment was deferred until early disease progression (71 vs 14 days). In patients with advanced, refractory, sight-threatening disease, treatment with fomivirsen 330 microg once weekly for 3 weeks and then 330 microg every 2 weeks (n = 34) or 330 microg on days 1 and 15 and then monthly (n = 20) significantly delayed disease progression. The interpolated median time to disease progression was 90 days in both treatment groups. The most common adverse events reported in clinical trials of fomivirsen were increased intraocular pressure and mild to moderate intraocular inflammation. These events were generally transient or reversible with topical steroid treatment.

AIDS-Related Opportunistic Infections↗

PubMed1999

Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections.

UNLABELLED: Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia. Combination regimens of piperacillin/tazobactam plus an aminoglycoside are used to treat patients with severe nosocomial (hospital-acquired) infections. In clinical trials, piperacillin/tazobactam was significantly more effective than ticarcillin/clavulanic acid in terms of clinical and microbiological outcome in patients with community-acquired pneumonia. In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia). Piperacillin/tazobactam in combination with amikacin was at least as effective as ceftazidime plus amikacin in the treatment of ventilator-associated pneumonia and was significantly more effective than ceftazidime plus amikacin in the empirical treatment of febrile episodes in patients with neutropenia or granulocytopenia. In other trials, the efficacy of piperacillin/tazobactam was similar to that of standard aminoglycoside-containing and other treatment regimens in patients with intra-abdominal, skin/soft tissue or gynaecological infections. Piperacillin/tazobactam is generally well tolerated. The most frequent adverse events are gastrointestinal symptoms (most commonly diarrhoea) and skin reactions. The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy. CONCLUSION: Because of the broad spectrum of antibacterial activity provided by piperacillin/tazobactam, it is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria. Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group.

Bacterial Infections↗

PubMed1999

Topical imiquimod: a review of its use in genital warts.

UNLABELLED: Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-alpha and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of > or = 50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete or partial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of > or = 1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosuppressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in < or = 67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. CONCLUSION: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies. which are administered in the physician's office, imiquimod cream is a self-administered therapy for outpatient use.

Adjuvants, Immunologic↗

PubMed1999

Tegaserod.

Tegaserod is a serotonin (5-hydroxytryptamine; 5-HT) receptor partial agonist which has been investigated for the treatment of irritable bowel syndrome (IBS). Specifically, it binds with high affinity to human 5-HT4 receptors, thereby stimulating the release of neurotransmitters and the peristaltic reflex in vitro. Small bowel transit (increased colonic filling over 6 hours) was accelerated in patients with constipation-predominant irritable bowel syndrome (IBS) receiving oral tegaserod 2mg twice daily for 1 week compared with those receiving placebo. In addition, there was a mean 20% increase of proximal colonic emptying in these patients. Oral tegaserod 2 (p < 0.05) or 6mg twice daily improved symptoms of abdominal discomfort, bloating and constipation (assessed using a Subjects' Global Assessment Scale) compared with placebo in patients with constipation-predominant IBS in a double-blind, dose-ranging study. The most frequent adverse events in patients with constipation-predominant IBS receiving oral tegaserod were transient diarrhoea and flatulence. No clinically relevant changes in blood pressure, pulse rate, QRS or QTc interval were reported with tegaserod doses of 25 to 100mg.

Clinical Trials as Topic↗

PubMed1999

Gatifloxacin.

Gatifloxacin is a novel extended-spectrum fluoroquinolone with improved gram-positive and anaerobe coverage compared with older agents such as ciprofloxacin. It has good activity (but is slightly less active than ciprofloxacin) against Enterobacteriaceae. Gatifloxacin is generally 2- to 4-fold more active than ciprofloxacin against staphylococci, streptococci and enterococci and 4- to 16-fold more active than ciprofloxacin against anaerobes, including Clostridium and Bacteroides spp. In comparative clinical trials that included patients with lower respiratory tract, urinary tract, skin and soft tissue or gonococcal infections, clinical cure rates of > or = 89% were achieved with oral gatifloxacin 400 mg/day for 7 to 14 days. Data from a subset of North American patients included in a multinational trial showed that oral gatifloxacin 400 mg/day produced a significantly higher clinical cure rate than cefuroxime axetil 250 mg twice daily (89 vs 77%; p = 0.01) in patients with acute exacerbations of chronic bronchitis. The clinical efficacy of gatifloxacin was similar to that of clarithromycin or levofloxacin or ceftriaxone (with or without erythromycin) in the treatment of patients with community-acquired pneumonia. Oral gatifloxacin 400 mg/day showed clinical and bacteriological efficacy similar to that of levofloxacin in patients with skin and soft tissue infections. In patients with urinary tract infections, clinical cure and bacterial eradication rates achieved with a single 400 g oral dose of gatifloxacin were similar to those produced with ciprofloxacin. In a pooled analysis of tolerability data from trials that included 3021 patients treated with oral gatifloxacin 400 mg/day, the most commonly reported adverse events were nausea (8%), diarrhoea (4%), headache (4%) and dizziness (3%). The drug was reported to be well tolerated. Gatifloxacin does not appear to cause phototoxic effects.

Anti-Infective Agents↗

PubMed1999

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↗

PubMed1998

Coxsackievirus B3-induced myocarditis: perforin exacerbates disease, but plays no detectable role in virus clearance.

Viral myocarditis is remarkably common, being detected in approximately 1% of unselected asymptomatic individuals. Many cases are attributable to enteroviral infection, and in particular to coxsackievirus B3. The underlying pathogenesis is controversial, but most studies admit the important immunopathological role of infiltrating CD8+ (cytotoxic) T lymphocytes (CTLs). We have previously shown that CTLs play conflicting roles in coxsackievirus B (CVB) myocarditis; they assist in controlling virus replication, but also are instrumental in causing the extensive inflammatory disease, which often results in severe myocardial scarring. A role for perforin, the major CTL cytolytic protein, in CVB myocarditis has been suggested, but never proven. In the present study we use perforin knockout (PKO) mice to show that perforin plays a major role in CVB infection; in broad terms, perforin is important in immunopathology, but not in CVB clearance. For example, PKO mice are better able to withstand a normally lethal dose of CVB (100% survival of PKO mice compared with 90% death in +/+ littermates). In addition, PKO mice given a nonlethal dose of CVB develop only a mild myocarditis, whereas their perforin+ littermates have extensive myocardial lesions. The myocarditis in PKO mice resolves more quickly, and these mice show minimal histological sequelae; in contrast, late in disease the perforin+ mice develop severe myocardial fibrosis. PKO mice, despite lacking this major CTL effector function, can control the infection and eradicate the virus; growth kinetics and peak CVB titers are indistinguishable in PKO and perforin+ mice. Therefore, the immunopathological and antiviral effects of CTLs can be uncoupled by ablation of perforin; this offers a promising target for therapy of myocarditis. Furthermore, we evaluate the possible roles of apoptosis, and of chemokine expression, in CVB infection. In perforin+ mice, apoptotic cells are detected within the inflammatory infiltrate, whereas in their PKO counterparts, apoptotic myocyte nuclei are seen. Chemokine expression in both PKO and perforin+ mice precedes and parallels the course of myocarditis. Several chemokines are detectable earlier in PKO mice than in perforin+ mice, but PKO mice show reduced peak levels, and chemokine expression decays sooner. In particular, MIP-1alpha expression is barely detectable at any time point in PKO mice, but it is readily identified in perforin+ animals, peaking just before the time of maximal myocarditis; this is particularly interesting, given that MIP-1alpha knockout mice are resistant to CVB myocarditis, but remain able to control viral infection. Thus, the chemokine pathway offers a second route of intervention to diminish myocarditis and its sequelae, while permitting the host to eradicate the virus.

Animals↗

PubMed1998

Improving home care. A survey on physician and nurse communication.

Home health care is growing, and phone calls between physicians and home care nurses are essential to successful home care patient management. This preliminary study analyzed several aspects of the physician and home health nurse telephone communication, including effectiveness, time expenditure, percentage of calls resolved by physicians, and documentation of phone contacts between 90 medical/surgical physicians and six home health nurses in Cleveland, Ohio. The phone conversations involved 154 patient contacts during a 3-month period. Overall, we found 75% of the home calls were effective. Eighty-five percent of calls required 15 minutes or less for completion, 47% of nurse-generated calls were resolved by physicians, and 26% of calls were documented in the patient's medical record. Our results illuminated several aspects of home care communication amenable to improvement.

Communication↗

PubMed1998

Saquinavir soft-gel capsule formulation. A review of its use in patients with HIV infection.

Saquinavir is an HIV protease inhibitor which, formulated as a hard-gel capsule (HGC), was the first drug of its class to become available for the treatment of patients with HIV infection. Despite the beneficial effects that saquinavir HGC-containing combination regimens have shown in the treatment of patients with HIV infection, the HGC formulation has limited oral bioavailability and has shown only modest antiviral activity in vivo. To overcome this limitation (with the aim of improving antiviral efficacy), a soft-gel capsule (SGC) formulation of the drug has been developed. At the recommended dosage of 1200 mg 3 times daily, the SGC formulation of saquinavir achieves plasma concentrations > 8 times higher than those in patients receiving saquinavir HGC 600 mg 3 times daily. Initial results of trials evaluating the therapeutic efficacy of saquinavir SGC-containing combination therapy in patients with moderate to advanced HIV infection are promising. In patients who were previously antiretroviral therapy-naive or -experienced, short term (< or = 36 weeks) treatment with saquinavir SGC in combination with > or = 2 nucleoside reverse transcriptase inhibitors (NRTIs), or nelfinavir, or 2 NRTIs plus nelfinavir led to marked improvements in virological and immunological markers of HIV disease. In comparative trials, saquinavir SGC showed improved antiviral activity compared with the HGC formulation in terms of reducing viral load. Furthermore, saquinavir SGC in combination with 2 NRTIs was as effective as indinavir plus 2 NRTIs in antiretroviral-naive or -experienced patients. Available data suggest that saquinavir SGC-containing combination therapy may be of greatest benefit in patients naive to previous antiretroviral therapy. The SGC formulation of saquinavir appears to be generally well tolerated by adults with HIV infection. Gastrointestinal adverse events, notably diarrhoea, abdominal discomfort, nausea and dyspepsia, are the most common adverse events occurring during treatment with the drug. Initial results of several trials that used surrogate markers to assess treatment efficacy indicate that the SGC formulation of saquinavir, administered in combination with other antiretroviral drugs, is an effective and well-tolerated treatment for patients with moderate or advanced HIV infection. Although further data are required before definitive conclusions can be drawn regarding the comparative efficacy and tolerability of the SGC and HGC formulations, it appears likely that the SGC formulation will replace the conventional formulation as a component of combination regimens for the treatment of patients with HIV infection.

Anti-HIV Agents↗

PubMed1998

Sumatriptan. An updated review of its use in migraine.

UNLABELLED: Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.

Administration, Intranasal↗

PubMed1998

Voices from an Afghan community.

A major role of the community health nurse is advocating to meet the needs of population groups. This article describes how community health nurses utilized two assessment tools, a windshield survey, a semi-structured interview protocol, and the Healthy People 2000 National Health Objectives to collect pertinent information and recommend program strategies at the primary, secondary and tertiary prevention levels to reduce the prevalence of domestic violence in an Afghan community.

Adult↗

PubMed1997

Use of a nonviral vector to express a chimeric tRNA-ribozyme against lymphocytic choriomeningitis virus: cytoplasmic accumulation of a catalytically competent transcript but minimal antiviral effect.

RNA polymerase III promoters direct the ubiquitous, high-level, expression of small, stable RNAs such as tRNAs, and thus are attractive candidates for achieving stable expression of small therapeutic (e.g., antiviral) molecules, such as ribozymes or antisense RNAs. In this article, we describe the use of a nonviral vector containing a tRNA promoter to express an antilymphocytic choriomeningitis virus (LCMV) ribozyme (tRNA-Rib5). The chimeric tRNA-ribozyme is specifically and efficiently transcribed by pol III in cell-free extracts, and the resulting transcript has appropriate ribozyme activity. In tissue culture studies, high levels of chimeric transcripts were readily detectable and were transported to the cytoplasm, the site of LCMV replication. Despite accumulation of tRNA-Rib5 in the cytoplasm of stably transformed cell clones, antiviral effects were minimal or absent. The implications of these findings and the potential use of this vector system for in vivo studies requiring the delivery of small molecules are discussed.

3T3 Cells↗

PubMed1997

Lamivudine. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection.

Lamivudine is a dideoxynucleoside analogue which undergoes intracellular phosphorylation to the putative active metabolite, lamivudine triphosphate. Lamivudine triphosphate prevents HIV replication by competitively inhibiting viral reverse transcriptase. Lamivudine has a unique resistance profile and has the ability to delay resistance to zidovudine and restore zidovudine sensitivity in zidovudine-experienced patients. Combination antiretroviral drug therapy is now generally considered preferable to monotherapy as first-line treatment for patients with HIV infection. In double-blind trials in antiretroviral drug-experienced or -naive adults, improvements in surrogate markers of disease progression were significantly greater in patients receiving lamivudine plus zidovudine combination therapy than in patients who received either drug as monotherapy. Preliminary results of CAESAR, a large multicentre trial in patients with moderately advanced HIV infection receiving zidovudine-based treatment regimens, show a 54% reduction in the rate of disease progression or death with the addition of lamivudine, compared with the addition of placebo. Initial virological data from studies of combination regimens including lamivudine and protease inhibitors are also promising, although the longer term efficacy of these regimens remains to be established. Improvements in surrogate disease markers were also seen in children and adolescents with symptomatic HIV infection who received lamivudine monotherapy. Studies of lamivudine-containing combination therapy in children and adolescents are in progress, but few data have yet been published. Lamivudine is generally well tolerated as monotherapy or in combination with other antiretroviral agents in HIV-infected adults with CD4+ counts > or = 100 cells/microliter. Gastrointestinal disturbances were reported as the most common adverse events during lamivudine monotherapy or combination therapy. Lamivudine appears to be less well tolerated in patients with advanced disease (CD4+ cell counts < 100 cells/microliter), but more data are required to clarify its tolerability in such patients. Pancreatitis has been reported in children with advanced disease during treatment with the drug, but was not directly attributable to lamivudine therapy. Thus, lamivudine, administered in combination with zidovudine, is now established as an effective agent for the treatment of antiretroviral drug-experienced or -naive individuals with asymptomatic or symptomatic HIV disease. Moreover, encouraging preliminary data suggest that lamivudine is poised to become an important component of other regimens, in combination with drugs such as the protease inhibitors.

Adult↗

PubMed1997

Nelfinavir.

Nelfinavir is a protease inhibitor which shows good inhibitory activity against HIV-1. The pattern of HIV-1 resistance to nelfinavir is different from that seen with other protease inhibitors. In healthy male volunteers, administration of single 400 and 800mg doses of nelfinavir with food resulted in area under the plasma concentration-time curve values that were 27 to 50% higher than those achieved in fasted volunteers who received the same doses of the drug. Reductions in plasma HIV RNA to below detectable levels (detection limit 500 copies/ml) were achieved in some patients (number not reported) after 28 days' treatment with nelfinavir 500, 600 or 750 mg twice daily, or 500, 750 or 1000 mg 3 times daily. Combination therapy with nelfinavir and stavudine produced greater reductions in plasma HIV RNA levels that stavudine monotherapy in patients who had not previously received stavudine treatment; mean increases in CD4+ cell counts were also greater in the combination treatment group than in monotherapy recipients. Plasma HIV RNA decreased to below detectable levels in 11 of 12 patients with early onset HIV infection who received a triple regimen of nelfinavir, zidovudine and lamivudine for 16 weeks.

Anti-HIV Agents↗

PubMed1997

Ganciclovir. A pharmacoeconomic review of its use as intravenous or oral maintenance therapy in the management of cytomegalovirus retinitis in patients with AIDS.

Cytomegalovirus retinitis, an opportunistic infection caused by the herpesvirus cytomegalovirus, is a major cause of illness in patients with advanced AIDS. As infected patients require long term drug treatment to delay disease progression and minimise loss of vision, the disease is associated with substantial treatment costs which considerably increase overall expenditure on AIDS-related health care. During the last decade, intravenous ganciclovir has been a mainstay of treatment for patients with cytomegalovirus retinitis. However, notwithstanding its demonstrated efficacy as maintenance therapy for this condition, long term intravenous drug administration is both inconvenient and uncomfortable for many patients. Moreover, neutropenia and catheter-related infections have been reported commonly in patients receiving ganciclovir via the intravenous route. To overcome the limitations of intravenous ganciclovir, an oral formulation of the drug has been developed for use as maintenance therapy. In comparative clinical trials, both intravenous and oral ganciclovir maintenance therapy slowed disease progression and preserved visual acuity in patients with stabilised cytomegalo-virus retinitis, although there was evidence that the intravenous formulation was more effective in terms of delaying recurrence of active disease. This suggests that oral ganciclovir use should be limited to the treatment of patients without evidence of immediately sight-threatening cytomegalovirus retinitis. Three published cost analyses, which were based on efficacy and tolerability data derived from 2 randomised, comparative clinical trials, have shown that oral ganciclovir maintenance therapy offers cost advantages over intravenous maintenance therapy, despite the higher acquisition cost of the oral formulation. The higher overall costs of intravenous maintenance treatment, compared with oral therapy, were attributed to higher drug administration and adverse event treatment costs. In one analysis, estimated lifetime treatment costs of oral maintenance therapy were 25.2% lower than those of intravenous maintenance treatment. As yet, no formal cost-effectiveness evaluations of oral and intravenous ganciclovir have been published. Few published data are available regarding the relative effects of intravenous and oral ganciclovir on quality of life. However, in a health state utility analysis, there was a large overall preference among HIV-infected individuals for oral over intravenous maintenance treatment. In conclusion, oral ganciclovir appears to be a cost-saving and patient-preferred alternative to its intravenous counterpart for the maintenance therapy of AIDS patients with stabilised cytomegalovirus retinitis in whom there is no evidence of sight-threatening disease.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Nursing student practicums in home care.

In the next decades home care will become the setting of choice for health care delivery. Because of this trend, nursing education must begin offering a home care component to nursing degree candidates. One such program strives to better prepare students for the unique care delivery that in-home care demands.

California↗

PubMed1996

Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in benign gynaecological disorders.

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which, during continuous administration, down-regulates the pituitary-ovarian gonadal axis and reduces levels of the gonadotrophins, luteinising hormone and follicle-stimulating hormone. In women, this results in suppression of ovarian steroidogenesis and a decline in estrogen to levels similar to those observed after menopause or following surgical oophorectomy. Thus, goserelin has a useful role in the management of some benign estrogen-dependent gynaecological disorders. Goserelin is available as a biodegradable sustained release depot 3.6mg injection which is administered every 28 days. In women with endometriosis, monthly injections of depot goserelin were effective in achieving resolution of endometriotic implants and in improving pelvic symptoms, including pain and dyspareunia. Randomised clinical comparisons of depot goserelin with danazol indicate that goserelin is at least as effective as danazol and is better tolerated in the treatment of endometriosis. In the management of uterine leiomyomata (fibroids), goserelin depot injections reduce uterine size and the size of uterine leiomyomata, with maximum clinical benefit achieved approximately 3 to 4 months after initiation of treatment. When used as an adjunctive pretreatment for women undergoing surgical removal of uterine leiomyomata, goserelin was associated with technically easier surgical procedures, reduced intraoperative blood loss and reduced transfusion requirements around the time of surgery. As an alternative to surgery, therapeutic use of goserelin is limited by the rapid regrowth of leiomyomata following cessation of treatment. However, goserelin may be a useful treatment for women approaching menopause, in whom uterine leiomyomata shrink naturally as endogenous estrogen levels decline. In women with dysfunctional uterine bleeding, treatment with depot goserelin before surgery facilitates resection and ablative procedures by suppressing endometrial growth and thinning the endometrial mucosa. Goserelin is also an effective alternative to surgery in this patient group. As adjuvant therapy for women undergoing assisted reproduction procedures, goserelin is associated with reduced cycle cancellation rates and with an increase in the rate of oocyte retrieval. The tolerability profile of goserelin is characterised by adverse effects typical of hypoestrogenism, including hot flushes, loss of libido and loss of bone mineral density. However, concomitant 'add-back' hormone replacement therapy appears to effectively reduce these hypoestrogenic symptoms. In summary, the availability of depot goserelin has broadened the spectrum of effective treatments for benign estrogen-dependent gynaecological disorders. As goserelin is effective as a sustained release depot formulation suitable for administration on a monthly basis, it is also a convenient and practical treatment choice.

Antineoplastic Agents, Hormonal↗

PubMed1996

Cefuroxime axetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Cefuroxime axetil is an oral cephalosporin which is rapidly hydrolysed to the active parent compound, cefuroxime. Cefuroxime has a broad spectrum of in vitro antibacterial activity which encompasses methicillin-sensitive staphylococci and the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and group A beta-haemolytic streptococci. Cefuroxime has broad spectrum activity against the beta-lactamase positive respiratory pathogens H. influenzae and M. catarrhalis; it is also active against penicillin-susceptible and -intermediate strains of S. pneumoniae. In clinical trials, cefuroxime axetil (administered twice daily) has been evaluated in the treatment of upper and lower respiratory tract infections and has demonstrated similar efficacy to established antibacterial agents, including amoxicillin/clavulanic acid and cefaclor. Five days' treatment with cefuroxime axetil was recently shown to be as effective as 10 days' treatment with either cefuroxime axetil or amoxicillin/clavulanic acid in patients with acute otitis media or acute bronchitis. Cefuroxime axetil was at least as effective as phenoxymethylpenicillin (penicillin V) in the treatment of patients with group A beta-haemolytic streptococcal tonsillopharyngitis. A number of studies have evaluated the efficacy of cefuroxime axetil as the oral component of intravenous to oral sequential therapy in hospitalised patients with lower respiratory tract infection. In each study patients received parenteral cefuroxime for approximately 2 days followed by cefuroxime axetil for 5 to 10 days. In comparative studies, cefuroxime sequential therapy was as effective as amoxicillin/ clavulanic acid sequential therapy and full courses of parenteral cefuroxime, cefotiam or cefoperazone. Adults with urinary tract infections and skin infections were also effectively treated with cefuroxime axetil, as were adults and adolescents with early stage lyme disease. Cefuroxime axetil is associated with a low incidence of adverse events, with gastrointestinal disturbances being the most frequently observed. Thus, cefuroxime axetil is an effective and convenient treatment for a wide range of infections and may be considered a therapeutic option when empirical treatment of community-acquired infections is required. Moreover, given the promising results of several intravenous/oral sequential treatment studies, cefuroxime axetil may also become established as an oral component of sequential treatment regimens.

Age Factors↗