Search PubMed⌕ Search

Biomedical subjects

M Youle

Publications and source records attributed to M Youle.

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

Measuring the effect of clinical guidelines on patient outcomes.

OBJECTIVES: To identify and examine the methodologic issues related to evaluating the effectiveness of treatment adherence to clinical guidelines. The example of antiretroviral therapy guidelines for human immunodeficiency virus (HIV) disease is used to illustrate the points. METHODS: Regression analysis was applied to observational HIV clinic data for patients with CD4+ cell counts less than 500 per microL and greater than 50 per microL at baseline (n = 704), using Cox proportional hazards time-varying covariates models controlling for baseline risk. The results are compared with simpler models (Cox model [without time-varying covariates] and logistic regression). In addition, the effect of including a measure of exposure to antiretroviral guidelines in the model is explored. RESULTS: This study has three implications for modeling clinical guideline effectiveness. To capture events that are time-sensitive, a duration model should be used, and covariates that are time-varying should be modeled as time-varying. Thirdly, incorporating a threshold measure of exposure to reflect the minimum period of time for guideline adherence required for a measurable effect on patient outcome should be considered. CONCLUSIONS: The methods proposed in this paper are important to consider if guidelines are to evolve from being a tool for summarizing and transferring the results of research from the literature to clinicians into a practical tool that influences clinical practice patterns. However, the methodology tested in this study needs to be validated using additional data on similar patients and using data on patients with other diseases.

Anti-HIV Agents↗
PubMed2000

Participation in clinical studies among patients infected with HIV-1 in a single treatment centre over 12 years.

OBJECTIVE: To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV-positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow-up visit were included. METHODS: The demographics of those participating in a clinical study were compared to those not enrolling using chi2 tests and Wilcoxon tests. Cox models were used to determine factors related to participation in clinical studies. RESULTS: Data from 2703 patients representing 5342.7 person-years' follow-up were assessed. Median time of follow-up was 23.6 months. Six hundred and eighty-seven (33%) patients had ever participated in a clinical study. After adjustment for demographic factors in multivariate analysis using Cox models, homosexuals were more likely to participate compared with heterosexuals or injecting drug users (IDU) (P = 0.0035 and P = 0.0001, respectively). Women were more likely to enter a study (P = 0.02) and there was no difference between Caucasians and black Africans (P = 0.35). Between the three types of studies few differences were seen. CONCLUSION: High rates of participation in clinical trials and epidemiological studies were seen in this cohort. In keeping with other studies, homosexual men were well represented but IDU were under-represented. However, women and black African patients showed good uptake of all clinical studies. Hence in this population there is some success in targeting representative groups to participate in clinical studies, but more effort needs to be made with IDU.

AIDS-Related Opportunistic Infections↗
PubMed2000

Amyl nitrite induced acute haemolytic anaemia in HIV-antibody positive man.

Volatile nitrites (amyl and butyl) are popular recreational drugs, especially in the homosexual population. Haemolytic anaemia is a rare complication of nitrite inhalation and occurs when the reducing capacity of the red cell enzymes is overcome by the oxidizing effect of the nitrite. We describe here a patient with HIV infection who developed a profound haemolytic anaemia after repeated inhalation of large quantities of amyl nitrite.

Acute Disease↗
PubMed1999

Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy.

OBJECTIVE: To investigate the rate of decline of drug resistant viruses after stopping therapy. DESIGN: Twenty-five patients receiving multiple combination therapies (mean five; range three to nine drugs) for more than 3 months were tested for HIV-1 resistance on therapy and off therapy. The sample off therapy was tested 6-175 days after stopping therapy. METHODS: Patients were tested for genotypic changes associated with drug resistance using an in-house automated DNA sequencing assay to detect resistance in the protease and reverse transcriptase genes. RESULTS: All samples tested when patients were on therapy showed evidence of drug resistance (range 1-9 mutations). The patients were divided into three groups: <2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks-2 months, median 6.4 weeks (n = 7, group B) and 2 months-6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 461/L, 82A, 90M; reverse transcriptase: 70R, 184I/V, 215 Y/F) detected on therapy 100% remained after stopping therapy in group A; 68% remained in group B and 15% remained in group C. For secondary mutations 98% remained in group A; 99% remained in group B and 57% in group C. CONCLUSIONS: This study showed a rapid decline in detectability of the majority of primary mutations within 13 weeks of stopping combination therapy. From this data, HIV-1 resistance testing to direct patients' therapy should only be carried out when on existing therapy, or < 2 weeks off therapy, if reliable decisions are to be made relating to future combinations.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Health economics. Perfect combination.

The assumption by some HAs that a shift from mono to combination drug therapies for HIV results in a proportional increase in drug expenditure, regardless of health gains, is misguided. Methods of calculating anti-HIV drug expenditure have failed to keep up with changing treatment regimes. There is an urgent need to change the way data on antiretroviral use is collected and presented to establish the true cost-effectiveness of new drug regimes.

Anti-HIV Agents↗
PubMed1999

Changes in AIDS-defining illnesses in a London Clinic, 1987-1998.

OBJECTIVES: To describe the incidence of AIDS-defining illnesses within a single large clinic setting, to describe temporal changes over a 10-year period in the overall incidence and of individual AIDS-defining illnesses and to investigate the impact of HIV treatment regimen on the incidence of AIDS-defining illnesses. SUBJECTS AND METHODS: A person-years analysis was used to determine the incidence of AIDS-defining illnesses according to calendar year and stratification by CD4 lymphocyte count and treatment regimen in 1806 patients from the Royal Free Centre for HIV Medicine with at least one CD4 lymphocyte count and follow-up visit. RESULTS: Prior to 1992, the incidence of all AIDS-defining illnesses was 27.4/100 person-years of follow-up (PYFU; 95% confidence interval [CI], 22.8-32.0) and during 1997 this incidence had dropped to 6.9/100 PYFU (95% CI, 4.7-9.1; p < .0001, test for trend). The decline in incidence over time occurred in esophageal candidiasis, cytomegalovirus disease (including retinitis), Kaposi's sarcoma, lymphoma, wasting syndrome, and Pneumocystis carinii pneumonia (p < .05, test for trend), but there was no evidence of a decline in AIDS dementia or in Mycobacterium avium complex. In 1997, among patients with CD4 lymphocyte counts of < or =200 cells/mm3, the incidence rates for any AIDS-defining illness was 51.1/100 PYFU for patients taking no therapy (95% CI, 27.9-85.7), 34.5 among patients on monotherapy (95% CI, 4.2-124.6), 13.2 among patients taking dual combination therapy (95% CI, 3.6-33.8) and 6.1 among patients taking triple therapy or more complex regimens (95% CI, 0.7-22.0; p < .0001, test for trend). CONCLUSIONS: There was a considerable decline in AIDS-defining illnesses during 1996 and 1997, coinciding with the rapid development of new antiretroviral treatments and combinations of treatment. Further follow-up of large observational cohorts is essential to monitor the incidence of diagnoses less common than we were able to consider, such as tuberculosis, cryptosporidiosis, and cryptococcosis, and also to investigate whether the incidence of disease continues to fall, or whether it starts to rise again, as toxicities, compliance, drug resistance, and long-term side effects begin to appear.

AIDS Dementia Complex↗
PubMed1999

The changing pattern of admissions to a London hospital of patients with HIV: 1988-1997. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the changes over time in incidence of hospital admissions among patients with HIV, reasons for hospital admission, duration of stay, relationship with CD4 T-cell count and with antiretroviral treatment. METHODS: The incidence of hospital admissions during each calendar year from 1988 to 1997 inclusive was calculated using a person-years analysis. In addition the proportion of patient follow-up spent in hospital and the impact of changing treatment regimens among all patients with HIV aged > or = 14 years and with at least one CD4 T-cell count seen at the Royal Free Hospital, London was also described. RESULTS: A total of 1806 patients were investigated with median follow-up of 21.1 months. Among all patients, the proportion of follow-up time spent as an in-patient decreased from 3.9% in 1988 to 1.3% in 1997 (P = 0.0015; test for trend). Hospital admissions for any cause peaked during 1989 at 72.0 per 100 patient years of follow-up (PYFU) and was 28.5 per 100 PYFU during 1997 (P < 0.0001; test for trend). There was a statistically significant decline in the proportion of follow-up time spent as an in-patient among patients with CD4 T-cell counts of < 50 x 10(6)/l from > 30% before 1990 to < 5% during 1997 (P = 0.026; test for trend). Hospital admissions varied greatly according to treatment regimen; in 1996 and 1997 just 0.1% of follow-up time of patients on triple antiretroviral treatment regimens was spent as a hospital admission. CONCLUSIONS: Admissions to hospital began falling before the introduction of combination therapy and declined strikingly during 1996 and 1997 following the introduction of highly active antiretroviral therapy. These results have important implications for future allocation of resources and for patient management.

Adult↗
PubMed1999

Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease.

OBJECTIVE: To report a novel clinical presentation: a chronic erosive herpes simplex virus (HSV) infection of the penis which developed in AIDS patients following the commencement of highly active antiretroviral therapy (HAART). The lesions were unresponsive to antiviral treatments which had previously been effective, and this could not be accounted for in terms of increased antiviral resistance. DESIGN: Detailed case-note review and investigation of three cases which presented at two large HIV units in London. METHODS: Review of all histology with immunohistochemistry for HSV, HSV drug susceptibility assays, tissue typing and measurement of in vitro lymphocyte functional activity against HSV. RESULTS: The histology of the lesions was the same in each case, with the presence of HSV on immunohistochemistry and an unusual prominence of plasma cell and eosinophils in the inflammatory infiltrate. HSV-specific lymphoproliferative responses were normal in two cases, but subnormal in a third case. All individuals shared the HLA class I molecules B72 and Cw0202 and the class II allele DRB4. CONCLUSION: We believe this to be a previously unreported adverse consequence of HAART, the result of partial immune restoration, reminiscent of the the recently described syndrome of immune recovery vitritis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Changing treatment patterns among patients with HIV: Royal Free Hospital 1987-97.

OBJECTIVE: Following the publication of results of large-scale clinical trials, antiretroviral treatment for HIV has changed dramatically. The aim of this study was to describe changes in antiretroviral treatment and the way treatments were combined among 1806 patients with HIV seen at a single centre at the Royal Free Hospital, London, UK. DESIGN AND METHOD: Each calendar year was divided into quarters, and the number of patients receiving treatment and participating in clinical trials was determined. RESULTS: The proportion of patients on no therapy decreased from over 90% at the beginning of 1988 to under 15% at the end of 1997. Monotherapy was the only form of treatment available before 1992 but its use dropped to 2% by the end of 1997. The standard of care at the end of 1997 was triple combination therapy, used in over 40% of patients. There were dramatic changes in the use of individual agents; use of zidovudine decreased from 50% during 1989 to 25% during 1997, while use of lamivudine and stavudine saw an exponential rise in 1997. The protease inhibitors were used in equal proportions in this clinic population; the use of dual protease therapy began in 1997 and was rising rapidly by the end of the year. CONCLUSIONS: There have been major changes in the use of antiretroviral therapy at this centre, particularly during 1996 and 1997. The long-term cost implications and side-effects of intensive treatment regimens remain to be addressed.

Adult↗
PubMed1999

Poor reduction of HIV-1 RNA titres in nucleoside reverse transcriptase inhibitor experienced patients treated with indinavir combination therapy.

OBJECTIVES: The long term effectiveness of combination therapy at reducing viral loads in seminal fluid and blood plasma obtained from HIV-1 infected men who had undergone previous antiretroviral therapy was assessed. METHODS: Samples of semen and blood were obtained from a cohort of 12 nucleoside reverse transcriptase inhibitor experienced men before and during 25-68 weeks of combination therapy, which included the protease inhibitor indinavir. HIV-1 RNA titres present in the cell free blood and seminal plasma samples were determined using the nucleic acid sequence based amplification (NASBA)/Nuclisens assay system. RESULTS: Viral RNA was detected in 9/12 and 7/12 baseline blood plasma and seminal plasma samples, with median viral titres of 10(4.81) and 10(4.56) per ml, respectively. By the end of the study period the detection rates of HIV RNA in the blood and seminal plasma samples were 5/12 and 2/12, respectively, with the median viral titres below the assay cut off level for both sample types. Of the nine patients who had detectable viral RNA in the baseline sample, only three cleared virus from both compartments by the end of the study. CONCLUSIONS: These data show that stable reduction of blood and seminal fluid viral titres is not achievable in a significant proportion of nucleoside reverse transcriptase inhibitor experienced men.

Drug Therapy, Combination↗
PubMed1999

Health economics in HIV disease. A review of the European literature.

The costs of providing healthcare resources for patients with HIV disease have continued to rise during the last 2 decades since the first outbreak of AIDS. Although new and effective therapies have become available during this time, and are increasingly being used, outcome measures for, and the economic consequences of, differing models of care are poorly documented or understood. Most available economic and clinical data, especially data documenting post-therapy outcomes, are from small, short term studies. This has led to the use of modelling to estimate which determinants can improve the quality and cost effectiveness of HIV care in the future. Although the attempt to provide what is currently perceived to be the standard of care is stretching many healthcare budgets, it is an anachronism that there are few studies of health economics in HIV disease. Most published data relate only to North America, and there remains a paucity of European studies. This paper provides a review of the available data from Europe and attempts to highlight the trends that have taken place to date.

Cost of Illness↗
PubMed1999

A prospective evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing antiretroviral treatment regimens in HIV infection. European perspective.

BACKGROUND: A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that adding lamivudine to zidovudine-containing regimens for 1 year reduced progression to AIDS or death and, in addition, significantly reduced the number of hospitalisations, unscheduled outpatient visits and the requirement for medications for HIV-related illness. Data from all 1840 patients included in the intent-to-treat population of the CAESAR trial were used in the analysis reported in this paper. Because a third-party payer perspective was adopted, possible savings associated with increased productivity (indirect costs) were not taken into account. All costs were adjusted to 1997 prices. RESULTS: The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 3045 Deutschmarks (DM) [German analysis] or 432 pounds sterling (Pound) [UK analysis] per patient for the 1-year time period. These savings partly offset the cost of lamivudine in the 2 countries. The German analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of DM22,405 [95% confidence interval (CI): -DM2199 to DM59,154] for progression to AIDS/death avoided and of DM8869 (95% CI: -DM1047 to DM23,365) for HIV-related illness avoided. The corresponding ratios for the UK analysis were 12,030 Pounds (95% CI: 6752 Pounds to 21,888 Pounds) for progressions avoided and 4762 Pounds (95% CI: 2796 Pounds to 9484 Pounds) for new and recurrent 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 during the period that the treatment is effective. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.

Adult↗
PubMed1999

Health economics in HIV disease.

All illnesses and, by association, all provision of health care in any setting have a cost, whether it is the direct cost to the consumer, to the provider (for example, a national health service) or the indirect cost to an employer or to society in lost production. Disease also has hidden or intangible costs of pain, suffering, and distress for the people affected and for their surrounding support structure such as family and friends. The ability to provide what is currently perceived as the treatment standard of care, in human immunodeficiency virus (HIV) disease, is stretching many health care budgets globally, yet few studies of health economics have been conducted in this area. Such studies are needed and increasingly will become a vital resource regarding health care costs and utilization for optimal provision of health care in HIV disease.

Cost-Benefit Analysis↗