PubMed Health⌕ Search

Biomedical subjects

V Miller

Publications and source records attributed to V Miller.

At least 73 records · Page 4Linked to original sources
PubMed2000

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Virological failure among patients on HAART from across Europe: results from the EuroSIDA study.

OBJECTIVES: To monitor the response to highly active antiretroviral therapy (HAART) over time and the proportions of patients with poor virological control in order to help provide some insight into drug resistance. DESIGN: Analysis of data from the EuroSIDA study; an observational study initiated in 1994 of almost 8500 patients with HIV from across Europe. METHODS: Patients who initiated HAART, and had both a CD4 lymphocyte count and viral load measured in the 3 months prior to starting HAART, were included in analyses. The proportion of patients with a poor virological response (defined as a viral load of > 10,000 copies/ml, using either a single measure or two consecutive measures) at 16 and 48 weeks was determined. Multivariate logistical regression was used to determine the factors associated with a poor virological response at both time points. RESULTS: Median CD4 cell count at starting HAART was 218 cells/mm3 [interquartile range (IQR), 113-327 cells/mm3] and median viral load was 4.36 log10 copies/ml (IQR, 3.57-5.04 log10 copies/ml). At 16 weeks, 16% had a viral load of > 10,000 copies/ml based on a single viral load measure and 10% if the more stringent definition of two consecutive viral loads above this level was used. At 48 weeks these proportions were 19% and 13%, respectively. Compared with patients from Southern Europe, patients from both Central and Northern Europe had approximately half the chance of a poor virological response at 16 weeks (odds ratios 0.53 and 0.47, P = 0.0015 and P < 0.0001, respectively), while at 48 weeks both regions still had approximately a 25% reduced chance of a poor virological response, but this was no longer statistically significant (odds ratio 0.77 and 0.75, P = 0.17 and P = 0.13, respectively). CONCLUSIONS: There were marked difference in virological response to HAART across regions of Europe, which may be partly explained by regional differences in access to HAART and utilisation. If drug resistance is closely related to virological failure, these results may help to provide an early insight into the potential problem of drug resistance across Europe. Continued follow-up is essential to monitor patients with poor virological control.

Anti-HIV Agents↗
PubMed1999

Regional survival differences across Europe in HIV-positive people: the EuroSIDA study.

OBJECTIVES: To analyse the survival differences between macro-regions of Europe (northern, central and southern Europe) between 1994 and early 1999, and their possible association with antiretroviral treatment differences. DESIGN: From September 1994 the EuroSIDA study has prospectively followed non-selected HIV-infected people from 50 clinical sites in 18 European countries (n = 7331). METHODS: Cox proportional hazards models were used to compare death rates between regions and to investigate the relationship between treatment usage and regional mortality rates. Kaplan-Meier curves were used to compare survival from the first CD4 lymphocyte count of < 200 x 10(6)/l or < 50 x 10(6)/l. RESULTS: At the time of analysis, the median follow-up was 21 months and there was a total of 1544 deaths. In people with a CD4+ cell count that fell below 200 or 50 x 10(6)/l those from central Europe had a better prognosis compared with those from the two other regions (P < 0.05). Patients from central Europe were more frequently exposed to reverse transcriptase inhibitors and protease inhibitors compared with patients from other regions (P < 0.001). There was a significant difference in risk of death between regions after adjustment for baseline differences in demography, presence of AIDS and level of immunodeficiency (risk of death in central Europe was 37% lower than that in southern Europe (P < 0.0001) and 33% lower than in northern Europe (P < 0.0001)). After adjustment for use of individual antiretroviral agents, intensity of treatment regimen, CD4 lymphocyte count, weight, haemoglobin and development of AIDS as time-dependent covariates, the differences became much smaller (risk in central Europe 13% lower than that in southern Europe (P = 0.071) and 15% lower than in northern Europe (P = 0.054). CONCLUSION: Antiretroviral therapy has been used more aggressively in Europe in recent years, resulting in improved prognosis. In this study we observed that the HIV mortality rate in central Europe was significantly lower than those in northern and southern Europe in the period 1994 to early 1999. This finding appears to be due to the effect on survival of different treatment policies and drug availability in the three regions of Europe during this time period, with central European countries, on average, having introduced more aggressive treatment strategies earlier.

Adult↗
PubMed1999

Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy.

OBJECTIVE: HIV-induced CD4 lymphocyte depletion is partially reversed by antiretroviral therapy but it is unclear if the degree to which the CD4 count rises depends on viral suppression (if so, the extent of viral suppression required to achieve a maximal CD4 count rise), whether the rise is sustainable and whether it occurs in patients with CD4 count <10 x 10(6) cells/l. We aimed to address these issues. METHODS: We studied CD4 count and plasma HIV RNA values every 4 weeks for 72 weeks in 154 patients starting indinavir-containing regimens. RESULTS: Mean baseline HIV RNA and CD4 count were 4.8 log10 copies/ml and 180 x 10(6) cells/l, respectively. Overall, there was a mean increase in CD4 count of 143 x 10(6) cells/l by 72 weeks. The adjusted mean increase (adjusted for initial viral load, CD4 count and age) was strongly related to the mean viral suppression over the follow-up period (P < 0.0001). Importantly, there was a highly significant difference (P = 0.0004) in the rise in CD4 count between those with 2-3 log suppression (161 x 10(6) cells/l) and those with > 3 log suppression (314 x 10(6) cells/l; mean 3.6 log suppression in this group), suggesting that with even greater suppression the rise in CD4 lymphocytes may be still larger. We also studied whether CD4 counts were still rising after 72 weeks in patients with sustained suppression of at least 3 log in viral load. There was a significant (P = 0.004; paired t-test) rise in count of 43 x 10(6) cells/l between weeks 64 and 72 in these patients, suggesting that regeneration continues at least up to 72 weeks after therapy, provided virus replication continues to be suppressed. Patients with initial CD4 counts < 10 x 10(6) cells/l experienced no smaller rises than those at higher levels, even after adjustment for other factors. CONCLUSION: These results strongly support a direct causal relationship between HIV replication and CD4 lymphocyte count depletion. The rise in those with > 3 log suppression provides the best available indicator of the potential for natural CD4 regeneration in HIV-infected patients. However, since still greater CD4 count rises may be seen with more suppressive regimens, it may not be possible to study the intrinsic CD4 regenerative capacity until such regimens are available.

Adult↗
PubMed1999

Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study.

BACKGROUND: The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated. OBJECTIVE: To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3. DESIGN: Prospective, observational multicenter study. SETTING: 52 HIV outpatient clinics in Europe. PATIENTS: Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4). MEASUREMENTS: Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional hazards models. RESULTS: The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively. CONCLUSIONS: Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.

Adult↗
PubMed1999

Virological response to protease inhibitor therapy in an HIV clinic cohort.

OBJECTIVE: New antiretroviral strategies aim to reduce plasma HIV RNA (viral load) to below the limits of detectability of assays with the objective of reducing viral replication in order to stop or reverse the pathogenic process and prevent development of drug resistance. First use of a protease inhibitor might offer the most realistic chance of achieving this aim. Our objective was to study the virological response to protease inhibitors in patients taking them for the first time. METHODS: A total of 901 patients from a large outpatient clinic were followed a mean of 15 months from the time of starting a protease inhibitor until 1 May 1998. Viral load and CD4 cell count measurements were made on average every 34 days. RESULTS: Overall there was a 79% [95% confidence interval (CI), 76-82] probability of the patients achieving a viral load < 500 copies/ml by 24 weeks after starting the protease inhibitor. In a multiple Cox regression model, those with lower initial viral load [relative hazard (RH), 0.72; P < 0.0001], higher CD4 cell count (RH, 1.07; P = 0.002), those starting other new drugs at same time as the protease inhibitor (RH, 1.46 for two versus none; P = 0.003), those who were antiretroviral-naive, and those using indinavir or nelfinavir were more likely to achieve such levels. In those 651 patients achieving viral load < 500 copies/ml within 24 weeks, there was an estimated 53% (95% CI, 51-55) probability of rebound of viral load to > 500 copies/ml by 52 weeks from the first undetectable value. Again, those who had started other new drugs at the same time as the protease inhibitor (RH, 0.57; P = 0.003 for starting two versus none) tended to experience a lower probability of viral load rebound, as did those with higher initial CD4 cell count (RH, 0.87 per 100 x 10(6)/l higher; P = 0.0007). Those who took saquinavir achieved less durable virological responses than those who took other protease inhibitors. CONCLUSIONS: Starting protease inhibitor therapy with two other new antiretroviral drugs simultaneously with protease inhibitor therapy offers a better best chance of achieving sustained viral load < 500 copies/ml than starting fewer new drugs.

Adult↗
PubMed1999

Perioperative care of the older adult with auditory and visual changes.

Perioperative nurses can initiate measures during the perioperative period when working with older adults who have hearing and visual deficits. There are methods of assessing perioperative patients by interview and observation to provide indicators for nursing intervention. Caring and advocacy interventions include environmental modifications to enhance the patient's ability to hear, see, and understand what is happening during this anxiety-promoting time.

Age Factors↗
PubMed1999

Effects of age on distally and proximally generated drawing movements: a kinematic analysis of school children and adults.

The effects of age on basic fine motor functions were assessed using a kinematic analysis of simple repetitive drawing movements in a sample of 53 right-handed children aged 7 to 14 years 11 months and 16 adults aged 27 to 54 years with no detectable abnormality with neurological examination. Lines, circles, and half-circles were drawn at a self-chosen and maximum velocity with a pressure-sensitive pen on a computer graphics tablet. Patterns generated by finger, wrist, and arm movements, and those generated by combined finger-wrist movements with and without a change in the drawing direction were analysed. The frequencies of all movement patterns increased until adulthood: 0.1 Hz per year for half-circles, 0.15 to 0.2 Hz per year for circles and lines generated by arm and wrist movements. The greatest increase (0.35 Hz per year) was observed for lines produced by finger movements. Differences in movement frequencies between finger versus wrist or arm movements when drawing lines decreased from about 3 Hz in 7- to 8-year-olds to 0.5 to 1 Hz in adolescents. In adults the difference between maximum finger, wrist, and arm movement frequencies decreased to almost zero. In contrast, the differences in movement patterns with and without change in direction remained stable until adulthood. Based on these results it is hypothesized that the differential effects of finger and more proximally generated movements on age reflect maturation of distinct neuronal sites of the corticostriatal-cerebellar circuit rather than acquisition of motor skills or myelinization of corticospinal pathways.

Adolescent↗
PubMed1999

CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to </=500 copies/mL. The Kaplan-Meier method estimated viral rebound in 42.5% of patients by 24 weeks and in 64.3% by 84 weeks. Risk of viral rebound was independently associated with baseline and changes from baseline CD4 cell count. The achieved CD4 cell count was the most important factor for prediction of viral rebound (relative hazard, 5.4 for an updated CD4 cell count of <20 vs. >500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.

Adult↗
PubMed1999

Quality of life in children with Crohn's disease: a pilot study.

BACKGROUND: Focus group meetings were held with two groups, each containing 12 children with Crohn's disease aged 8 to 12 and 12 to 17 years. The children were asked broad questions about how Crohn's disease and its treatment affected their lives. To explore these areas in more detail, an 88-item questionnaire was developed and read to an additional 16 of 20 children with Crohn's disease selected at random from outpatients. At first, many of the children denied that Crohn's disease affected their lives at all, but it soon became apparent that many were frustrated or angry about physical symptoms, lack of understanding about Crohn's disease, unpleasant investigations, treatment, and hospitalisation. METHODS: The questionnaire covered six domains of health-related quality of life including symptoms and treatment, social, emotional, family, educational, and future aspects. RESULTS: Elemental diet was the preferred treatment, although surgery was more effective in controlling symptoms. Children receiving steroids had more depressive symptoms. Absenteeism from school and inability to engage in school sports, swimming, and running were frequent problems. There were also difficulties with taking holidays and staying at friends' houses. Worry was reported in 14 of 16 children, anger and frustration and feeling fed up in 12 of 16. CONCLUSIONS: In addition to being a symptomatically disabling condition, Crohn's disease has a great impact on the health-related quality of life of affected children. Future studies of treatment in children with inflammatory bowel disease should include an attempt to assess the impact on the child's health-related quality of life.

Adolescent↗
PubMed1999

Quality of life of parents and siblings of children with inflammatory bowel disease.

BACKGROUND: Few investigators have reported on the quality of life of family members of children with inflammatory bowel disease. Psychological symptoms have been reported in parents and siblings, but the problems that which give rise to these symptoms are seldom examined. In this pilot study, some of the issues that affect the quality of life of parents and siblings of children with inflammatory bowel disease were examined. METHODS: Focus group meetings were held separately with 20 parents and 7 siblings of children with inflammatory bowel disease. The participants were encouraged to identify voluntarily problems related to the disease that affected their lives, and the discussions were tape recorded. Each participant subsequently wrote down the three most important concerns. RESULTS: Thirteen (65%) parents were very concerned about the effect of the disease on the child's future jobs, marriage, independence) and 11 (55%) were worried about problems the ill child was encountering at school. Other issues of most concern to parents included side effects of medication (n = 7), limited job prospects (n = 3), persistent feelings of guilt (n = 3), and restricted family lifestyle (n = 1 ). Most siblings (57%) were concerned about their parents' keeping information about the illness from them, and three (43%) of them were also concerned about others bullying the ill child at school. Other issues of concern to siblings included fear about the disease and treatment (n = 3), parents overprotecting the ill child, and feelings of jealousy (n = 1). CONCLUSION: Families of children with inflammatory bowel disease experience many problems that may affect their quality of life. Resources should be made available to help families with these concerns.

Adolescent↗
PubMed1999

A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance.

To investigate the occurrence of multinucleoside analog resistance during therapy failure, we surveyed the drug susceptibilities and genotypes of nearly 900 human immunodeficiency virus type 1 (HIV-1) samples. For 302 of these, the 50% inhibitory concentrations of at least four of the approved nucleoside analogs had fourfold-or-greater increases. Genotypic analysis of the reverse transcriptase (RT)-coding regions from these samples revealed complex mutational patterns, including the previously recognized codon 151 multidrug resistance cluster. Surprisingly, high-level multinucleoside resistance was associated with a diverse family of amino acid insertions in addition to "conventional" point mutations. These insertions were found between RT codons 67 and 70 and were commonly 69Ser-(Ser-Ser) or 69Ser-(Ser-Gly). Treatment history information showed that a common factor for the development of these variants was AZT (3'-azido-3'-deoxythymidine, zidovudine) therapy in combination with 2',3'-dideoxyinosine or 2',3'-dideoxycytidine, although treatment patterns varied considerably. Site-directed mutagenesis studies confirmed that 69Ser-(Ser-Ser) in an AZT resistance mutational background conferred simultaneous resistance to multiple nucleoside analogs. The insertions are located in the "fingers" domain of RT. Modelling the 69Ser-(Ser-Ser) insertion into the RT structure demonstrated the profound direct effect that this change is likely to have in the nucleoside triphosphate binding site of the enzyme. Our data highlight the increasing problem of HIV-1 multidrug resistance and underline the importance of continued resistance surveillance with appropriate, sufficiently versatile genotyping technology and phenotypic drug susceptibility analysis.

Anti-HIV Agents↗
PubMed1999

An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets.

Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. Bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised.

3-Hydroxysteroid Dehydrogenases↗