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Biomedical subjects

M J Gill

Publications and source records attributed to M J Gill.

At least 37 records · Page 2Linked to original sources
PubMed2000

The momentary realist.

Research suggests that people initially take their subjective experience of an object as an accurate reflection of the object's properties, and only subsequently, occasionally, and effortfully consider the possibility that their experience was influenced by extraneous factors. The two studies reported here demonstrate that this is true even when the extraneous factors are the person's own dispositions. Dispositionally happy and unhappy participants were falsely told that they had been subliminally primed with words that might have influenced their moods, and were then asked to identify those words. Dispositionally happy participants were more likely than dispositionally unhappy participants to conclude that they had been primed with positive words, but only when they made these judgments under time pressure. The results are discussed in terms of correction models of human judgment.

Adult↗
PubMed2000

Long-term patient adherence to antiretroviral therapy.

OBJECTIVE: To measure patient adherence to antiretroviral therapy over a two-year period and to identify factors impacting adherence. METHODS: In a regional HIV treatment center, 100 consecutive patients starting any new antiretroviral agent were enrolled in this study, which consisted of a one-year retrospective data review and a one-year prospective component. The tools used for evaluating adherence were the monthly prescription refill data and a patient questionnaire. Data analyzed included overall adherence, adherence to individual antiretrovirals, and change in adherence over time, as well as factors reported as influencing adherence. RESULTS: Greater than 80% adherence in taking prescribed doses was seen in 75% of patients during the retrospective phase of the study; adherence increased to 84% in the prospective phase. Throughout the prospective phase of the study, monthly median adherence rates were 98-100%. Suboptimal adherence secondary to pill fatigue or number of daily pills did not occur. Reported nonadherence to dietary restrictions varied among drugs. The primary cause given for poor adherence was difficulty remembering followed by inconvenient dosing schedule and difficulty scheduling administration times around meals. At least one adherence tool was used by 61% of patients. A diagnosis of AIDS was associated with lower adherence in our patient population (p = 0.039); substance abuse and psychiatric history had no influence. CONCLUSIONS: Adherence to antiretroviral treatment regimens did not diminish over the two years studied. Several patients with poor adherence were identified, emphasizing the importance of addressing this issue both prior to and throughout treatment. A personalized approach by healthcare providers can optimize patient adherence to antiretroviral therapy by providing careful drug selection in addition to routine follow-up and the provision of information, feedback, and reminder systems.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Predictors of survival and eradication of Mycobacterium avium complex bacteremia (MAC) in AIDS patients in the Canadian randomized MAC treatment trial. Canadian HIV Trials Network Protocol 010 Study Group.

OBJECTIVE: To assess the importance of baseline characteristics including medical history, indicators of current disease status, therapeutic drug use, in vitro drug susceptibility, immune status and mycobacterial load on bacteriologic response and survival in HIV-positive patients with Mycobacterium avium complex (MAC) bacteremia. DESIGN: An observational substudy of an open-label randomized controlled trial of two alternative therapeutic regimens for MAC. SETTING: Twenty-four hospital-based HIV clinics in 16 Canadian cities. MAIN OUTCOME MEASURES: The main outcome measures were survival and bacteriologic response, defined by consecutive negative blood cultures for MAC at least 2 weeks apart within 16 weeks of study entry. RESULTS: Prior AIDS diagnosis, low Karnofsky score, active unstable AIDS-related conditions, absence of antiretroviral therapy and absence of Pneumocystis carinii pneumonia prophylaxis were associated with shorter survival by univariate regression using the proportional hazards model. On multivariate analysis, antiretroviral therapy was not an independent predictor of mortality, and previous rifabutin prophylaxis was independently associated with poor survival outcomes, a result consistent across study treatment. Using a logistic regression model, baseline quantitative mycobacterial load [relative odds of clearing, 1.97 for a decrease of 1 log10 colony forming count; 95% confidence interval (CI), 1.36-2.87; P < 0.001] and Karnofsky score were the only statistically significant univariate predictors of clearance, although previous prophylaxis with rifabutin was also a significant predictor in a multivariate model (relative odds of clearing, 0.39; 95% CI, 0.17-0.88; P < 0.05). CONCLUSIONS: This study indicates that although the level of MAC bacteremia is an important predictor of clearance, it is not associated with survival.

AIDS-Related Opportunistic Infections↗
PubMed1999

The use of antiretroviral agents in patients with renal insufficiency.

Current guidelines for the dosing of antiretroviral agents in HIV-positive patients with renal insufficiency including those requiring dialysis are limited, as revealed by a literature search performed using Health Knowledge Network MEDLINE and HealthSTAR. Pharmacokinetic and chemical aspects were taken into consideration to develop further recommendations. Results showed reverse transcriptase inhibitor dosage adjustment guidelines are available, but for patients receiving dialysis, guidelines are limited to zidovudine and didanosine. There are limited clinical data on dosage adjustments required for the use of protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Indinavir appears to require no dose modification. For nelfinavir, ritonavir and saquinavir, the chemical and pharmacokinetic characteristics along with the pathophysiology of renal dysfunction and dialysis suggest that these agents can likely be given at usual doses with close monitoring for toxicities. More data is required to make recommendations for use of NNRTIs in renal insufficiency. Combining the information from previous dosing guidelines and the pharmacokinetic data of antiretroviral agents allows for preliminary recommendations to be made until confirmed by definitive clinical data.

Anti-HIV Agents↗
PubMed1999

Plasmid heterogeneity and identification of a Tn5281-like element in clinical isolates of high-level gentamicin-resistant Enterococcus faecium isolated in the UK.

Ten clinical isolates of high-level gentamicin-resistant (HLGR) Enterococcus faecium, collected from six hospitals throughout the UK, were studied to determine whether HLGR was attributed to widespread dissemination of a single plasmid or whether different plasmid types were implicated in the dissemination of this phenotype. HLGR was attributed to the presence of the AAC6'-APH2" bifunctional aminoglycoside modifying enzyme. The aac6'-aph2" gene was present on a 70 kb plasmid in all ten isolates. Conjugation studies indicated that the HLGR marker could transfer with varying frequency, with or without the associated 70 kb plasmid. Detailed molecular genetic analysis suggested that four of the isolates harboured a transposon similar to Tn5281, originally identified in Enterococcus faecalis strain HH22 isolated in the USA. The UK transposon, however, lacked the two symmetrically located HaeIII sites found in Tn5281. The six remaining isolates appeared to have a Tn5281-truncated structure in which the aac6'-aph2" gene is flanked by an IS256 element at the 5' end. Further studies with nine restriction endonucleases showed that the aac6'-aph2" gene was associated with two different plasmid types in E. faecium. Pulsed-field gel electrophoresis (PFGE) analysis identified three different patterns. The four E. faecium isolates harbouring the Tn5281-like structure were indistinguishable from each other, while the remaining six isolates exhibited two distinct PFGE patterns. This is the first study to indicate that there is heterogeneity among the plasmids that confer the HLGR phenotype in E. faecium isolates in the UK and to report on the presence of a transposon, similar to Tn5281, in E. faecium harbouring the aac6'-aph2" gene.

Acetyltransferases↗
PubMed1999

Reduced glutaraldehyde susceptibility in Mycobacterium chelonae associated with altered cell wall polysaccharides.

Glutaraldehyde-resistant Mycobacterium chelonae have been isolated from endoscope washer disinfectors and endoscope rinse water. The mechanism of glutaraldehyde resistance is not well understood. Two spontaneous, glutaraldehyde-resistant mutants of the sensitive type strain, NCTC 946, were investigated. The colony morphology of the two mutants differed from that of the the type strain: colonies of the former were dry and waxy whereas those of the latter were smooth and shiny. Increased resistance to glutaraldehyde of the mutants was matched by small increases in the MICs of rifampicin and ethambutol but not isoniazid. Both mutants showed increased surface hydrophobicity. No changes were identified in the extractable fatty acids or the mycolic acid components of the cell wall but a reduction in each of the resistant strains in the arabinogalactan/arabinomannan portion of the cell wall was detected.

Aldehydes↗
PubMed1999

Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae.

An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.

Amino Acid Sequence↗
PubMed1999

Lamivudine reduces healthcare resource use when added to zidovudine-containing regimens in patients with HIV infection.

BACKGROUND: The impact on healthcare resource use of adding lamivudine to concurrent zidovudine-containing antiretroviral regimens was studied as a part of a 52-week multinational study [CAESAR (Canada, Australia, Europe and South Africa)] in HIV-infected patients with moderate to severe immunodeficiency (25 to 250 CD4+ cells/mm3). RESULTS: Significantly fewer lamivudine than placebo recipients required hospitalisations (p = 0.002), unscheduled outpatient visits (p = 0.013) or prescribed medications for HIV-related illness (p < 0.001). The mean number of hospitalisations and the mean duration of hospitalisation for HIV-related illness were 47% and 51% lower, respectively, with lamivudine than with placebo. The mean number of unscheduled outpatient visits was 32% lower with lamivudine than with placebo. Lamivudine was also associated with a significant reduction in the number of patients who were hospitalised (p = 0.04) or required unscheduled outpatient visits (p = 0.02) as a result of adverse events. CONCLUSIONS: Notwithstanding the fact that retrospective studies have suggested that more effective antiretroviral treatments reduce healthcare use, the CAESAR study is one of the few prospective controlled trials to demonstrate that by slowing disease progression with combination therapy it is possible to reduce healthcare resource use in patients with HIV infection. Although the combination of lamivudine and zidovudine alone is not likely to be sufficient to achieve complete long term suppression of viral replication and to halt disease progression, the study demonstrates the immediate economic benefits of preventing HIV progression in HIV-infected patients with moderate to severe immunodeficiency (25 to 250 CD4+ cells/mm3). These findings suggest that treatment regimens that slow progression of HIV infection have the potential to produce savings in non-drug healthcare costs, which may partly or fully offset the drug costs.

Adult↗
PubMed1999

An evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing regimens in HIV infection. Canadian perspective.

BACKGROUND: A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that the addition of lamivudine to zidovudine-containing regimens for 1 year reduced progression of HIV infection to AIDS or death, as well as significantly reducing the number of hospitalisations, outpatient visits and the requirement for medications for HIV-related illness and adverse events. Data from all 1840 patients included in the 'intent-to-treat' population of the CAESAR trial were used for the present analysis. A Canadian third-party payer perspective was adopted, and all costs were adjusted to 1997 prices. RESULTS: The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 1123 Canadian dollars ($Can) per patient, over the year. These savings partly offset the cost of lamivudine. The analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of $Can 14,225 [95% confidence interval (CI): $Can4383 to $Can29,577] for progression to AIDS/death avoided and of $Can5631 (95%CI: $Can2010 to $Can12,929) for HIV-related illness avoided. CONCLUSIONS: Our findings indicate that treatments that slow the progression of HIV infection to AIDS or death have the potential to facilitate healthcare savings, which partly offset the drug acquisition costs. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.

Adult↗
PubMed1998

Predictors of a viral response and subsequent virological treatment failure in patients with HIV starting a protease inhibitor.

OBJECTIVES: To investigate the factors related to viral load becoming undetectable among patients from Southern Alberta who started a protease inhibitor for the first time, and to determine the factors related to subsequent re-emergence of detectable viral load amongst those patients whose viral load initially became undetectable. SUBJECTS AND METHODS: A total of 243 patients from the Southern Alberta Clinic had started a protease inhibitor for the first time and had been followed up for a median time of 32 weeks. Standard survival techniques including Kaplan-Meier techniques and Cox proportional hazards models were used to determine which factors were related to viral load becoming undetectable. RESULTS: At 24 weeks after first exposure to a protease inhibitor, 52.8% of the patients [95% confidence interval (Cl), 45.2-56.6] had achieved an undetectable viral load. In a multivariate analysis, those with a higher initial viral load were less likely to become undetectable [relative hazard (RH), 0.50; 95% Cl, 0.35-0.70; P < 0.0001], whereas those starting more new drugs (RH per new drug, 1.54; 95% Cl, 1.01-2.11; P = 0.048) were significantly more likely to achieve an undetectable viral load. Amongst 111 patients whose viral load became undetectable, Kaplan-Meier analysis indicated that 15.5% of patients experienced re-emergence of detectable viral load at 24 weeks after the first undetectable viral load. A higher CD4 cell count was associated with a lower risk of viral load becoming detectable (RH, 0.73; 95% Cl, 0.53-1.00; P = 0.049), as was treatment with indinavir (versus any other protease inhibitor RH, 0.17; 95% Cl, 0.03-0.86; P = 0.033). CONCLUSIONS: A significant proportion of patients in a routine clinic setting achieved an undetectable viral load measurement after first starting a protease inhibitor; viral load in patients with a higher CD4 cell count was more likely to become and stay undetectable. There was no evidence that patients who were drug-naive experienced significantly worse virological effects than drug-experienced patients, as long as the same number of new drugs was started at the date of first exposure to a protease inhibitor. Further follow-up of these patients is warranted to study the longer term effects of treatment with protease inhibitors.

Adult↗
PubMed1998

Activity of the soft gelatin formulation of saquinavir in combination therapy in antiretroviral-naive patients. NV15355 Study Team.

OBJECTIVE: A Phase II, open-label, randomized, parallel-arm, multicentre trial to compare the antiviral activity and safety of two formulations of saquinavir (SQV), soft gelatin (SQV-SGC) and hard gelatin (SQV-HGC) capsules, in combination with two nucleoside reverse transcriptase inhibitors (NRTI), in antiretroviral-naive, HIV-1-infected individuals. PARTICIPANTS: A total of 171 people of > or = 13 years, with plasma HIV-1 RNA levels > or = 5000 copies/ml, who had received no protease inhibitor therapy, < or = 4 weeks NRTI therapy and no antiretroviral treatment within 28 days of screening. Eighty-one people were randomized to the SQV-HGC group and 90 to the SQV-SGC group. A total of 148 patients completed 16 weeks of therapy. INTERVENTION: Therapy for 16 weeks with either SQV-SGC 1200 mg or SQV-HGC 600 mg, both three times a day, in combination with two NRTI. RESULTS: Using an on-treatment analysis, patients taking SQV-SGC had a larger reduction in plasma HIV-1 RNA than those taking SQV-HGC (-2.0 versus -1.6 log10 copies/ml). Eighty per cent of those on SQV-SGC had < 400 copies HIV RNA/ml, compared with 43% in the SQV-HGC group (P = 0.001). A statistically significant difference in the area under the curve (AUC) values between the SQV-SGC and SQV-HGC arms (-1.7 versus -1.5 log10 copies/ml, respectively; P = 0.0054) was observed when withdrawals prior to week 12, major protocol violators and patients with < 75% compliance were excluded from the analysis; however, the difference between the values for the intent-to-treat population was not significant (P = 0.1929). Adverse events (mostly mild) included diarrhoea and nausea. CONCLUSIONS: SQV-SGC was generally well tolerated and gave significantly more potent suppression of plasma HIV-1 RNA in antiretroviral-naive patients than SQVHGC.

Adolescent↗
PubMed1998

Active immunization of patients with HIV infection: a study of the effect of VaxSyn, a recombinant HIV envelope subunit vaccine, on progression of immunodeficiency.

Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its administration was beneficial with respect to slowing disease progression. A 3-year multicenter, randomized, placebo-controlled, double-blinded, efficacy and safety trial of repeated immunization with VaxSyn was used to evaluate the long-term impact on the progression of immunodeficiency. VaxSyn in alum, or alum alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4 counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both virological and immunological parameters were followed. No significant differences were observed between the treatment and placebo control groups in rate of CD4 T cell decline, time to initiation of antiretroviral therapy, incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral infectivity as measured by quantitative HIV coculture assay, and death. This study revealed no effect on either clinical or laboratory virological parameters from the administration of VaxSyn.

AIDS Vaccines↗