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Long-term Clinical Follow-up (long-term + clinical_follow-up)
Selected AbstractsEvidence for prolonged clinical benefit from initial combination antiretroviral therapy: Delta extended follow-upHIV MEDICINE, Issue 3 2001Delta Coordinating Committee Background The findings from therapeutic trials in HIV infection with surrogate endpoints based on laboratory markers are only partially relevant for clinical decisions on treatment. Although the collection of clinical follow-up data from such a trial would be relatively straightforward, this rarely occurs. An important reason for this may be the perception that such data have little value because the number of participants remaining on their original allocated therapy has usually fallen substantially. Methods Delta was an international, multicentre trial in which 3207 HIV infected individuals were randomly allocated to treatment with zidovudine (ZDV) alone, ZDV combined with didanosine (ddI) or ZDV combined with zalcitabine (ddC). Although the trial closed in September 1995, information on vital status, AIDS events, treatment changes and CD4 counts was still collected every 12 months until at least March 1997. This has allowed analyses of the longer term clinical effect of treatment. Results The median follow-up to date of death or last known vital status was 43 months (10th percentile 18 months; 90th percentile 55 months). The proportion of participants remaining on their allocated treatment fell steadily over time; by 4 years after trial entry, 3% remained on ZDV, 20% on ZDV + ddI and 21% on ZDV + ddC. Changes mainly involved the stopping, addition or switching of a nucleoside reverse transcriptase inhibitor (NRTIs). There was little use of protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) before the third year of the trial. Between the third and fourth years, regimens included a drug from one of these classes for approximately 17% of person-time in all treatment groups. Relative to ZDV monotherapy, the beneficial effects of combination therapy on mortality and disease progression rates increased significantly with time since randomization. The maximum effects on mortality were observed between 2 and 3 years, with a 48% reduction for ZDV + ddI and a 26% reduction for ZDV + ddC. These rates were observed when the original allocated treatment was received 42% and 47% of the time in the ZDV + ddI and ZDV + ddC groups, respectively. The mean CD4 count remained significantly higher (approximately 50 cells/,L) in the combination therapy groups 4 years after randomization, suggesting a projection of a clinical benefit beyond this time point. Conclusions The sustained clinical effect of the initial allocation to combination therapy, particularly ZDV + ddI, was remarkable in light of the convergence of drug regimens actually received across the three treatment groups. Interpretation of this finding is not straightforward. One of the possible explanations is that the effectiveness of ddI and ddC is diminished if first used later in infection or with greater prior exposure to ZDV, although the data do not clearly support either hypothesis. This analysis highlights the value of long-term clinical follow-up of therapeutic trials in HIV infection, which should be considered in the planning of all new studies. [source] Highly sensitive detection of the MGB1 transcript (mammaglobin) in the peripheral blood of breast cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Nuno Cerveira Abstract We describe a new one-step RT-PCR assay for the detection of the mammaglobin (MGB1) gene transcript in the peripheral blood of breast cancer patients. With this approach, the MGB1 transcript could be detected in the peripheral blood of 22 of 54 (41%) breast cancer patients prior to any therapy. This method, using specific primers for cDNA synthesis, proved to be more sensitive (10,6 to 10,11, usually 10,7) than previously reported methodologies. This increased sensitivity was achieved without compromising specificity, as the MGB1 transcript was not detected in 38 blood samples of healthy donors and in only 1 of 18 blood samples of patients presenting with hematologic malignancies. A positive correlation was seen between MGB1 positivity and breast cancer stage: 0/3 (0%) in stage 0, 3/13 (23%) in stage I, 6/17 (35%) in stage II, 5/10 (50%) in stage III, 8/11 (73%) in stage IV (p = 0.003). The prognostic and therapeutic implications of MGB1 positivity by one-step RT-PCR in the peripheral blood of breast cancer patients, especially in clinically localized disease (stages I and II), should be evaluated after long-term clinical follow-up of these patients. © 2003 Wiley-Liss, Inc. [source] Large plaque parapsoriasis: clinical and genotypic correlationsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2000Martin Simon Twelve patients with large plaque parapsoriasis (LPP) were investigated for the presence of predominant T-cell clones, analyzing the T-cell receptor (TCR) ,-chain gene. The diagnostic and prognostic significance of TCR gene rearrangement status was assessed by a correlation with the long-term clinical follow-up. Six out of 12 patients showed a clonal T-cell population. Clinically, among the patients with clonal disease one developed clearcut mycosis fungoides (MF) after a follow-up of 8 years, in the other 5 patients no such diagnosis could be made after follow-up of 2,21 years (median: 9 years). In patients with polyclonal infiltrates the lesions remained virtually unchanged. These findings indicate that in LPP TCR gene rearrangement status has no prognostic significance and does not allow distinction of LPP and early MF. Both conditions show a clonal T-cell infiltrate with similar frequency, are very similar in clinical and histologic presentation and according to recent studies share the same low risk to develop overt MF. Therefore both terms refer to the identical clinical situation. This should be designated as early MF and efforts should concentrate on identifying those patients that are at risk to develop aggressive disease. [source] Idiopathic Hypercalcemia in CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2000A.M. Midkiff Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity, and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats. [source] Long-term outcome of tension-free vaginal tape for treating stress incontinence in women with neuropathic bladdersBJU INTERNATIONAL, Issue 6 2010Ahmad Abdul-Rahman Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate the long-term safety and efficacy of the tension-free vaginal tape (TVT) for the treatment of stress urinary incontinence (SUI) in women with neuropathic bladder dysfunction. PATIENTS AND METHODS Twelve women (mean age 53.3 years, range 41,80) with neuropathic bladder dysfunction and SUI confirmed by video-cystometrography (VCMG) were treated with a TVT in one institution by an expert neuro-urologist between November 1997 and December 2000. The patient's notes, clinical annual follow-up and VCMG after the procedure, and the incontinence impact questionnaire (IIQ) forms (Urinary Distress Inventory, and IIQ-7) were assessed during the long-term clinical follow-up for SUI, in addition to a health-related quality of life assessment. The cure of SUI was defined as no loss of urine on physical exercise, confirmed VCMG after the procedure, and by clinical assessment. RESULTS The mean (range) follow-up was 10 (8.5,12) years. Nine patients were using clean intermittent self-catheterization before the insertion of TVT and continued to do so afterward. At 10 years of follow-up, one patient had died (with failed TVT initially), and two were lost to follow-up at 5 years after surgery, but up to 5 years they did not complain of UI and VCMG did not show SUI. The remaining seven of the nine patients were completely dry, and two improved and were satisfied with using one or two pads/day. Two patients showed neurogenic detrusor overactivity confirmed on VCMG, with no evidence of SUI. One patient needed a transient urethral catheter for urinary retention after surgery, one had a bladder injury that required leaving the catheter for 5 days, but no urethral erosions were reported during the follow-up. CONCLUSIONS In women with neuropathic bladder dysfunction secondary to a variety of spinal cord pathologies, and who have SUI necessitating a definitive intervention, insertion of TVT should be considered a desirable treatment, with very good long-term outcomes. [source] COPS3 amplification and clinical outcome in osteosarcomaCANCER, Issue 9 2007Taiqiang Yan MD Abstract BACKGROUND. Amplification of several genes that map to a region of chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These genes were also shown to be overexpressed and may be involved in osteosarcoma tumorigenesis. COPS3 encodes a subunit of the COP9 signalosome implicated in the ubiquitination and ultimately degradation of the P53 tumor suppressor. To determine the relation between COPS3 amplification, P53 mutation, and patient outcome in osteosarcoma, tumors from a large cohort of patients with high-grade osteosarcoma and long-term clinical follow-up were examined. METHODS. Quantitative real-time polymerase chain reaction (PCR) was performed to detect copy number changes for COPS3, as well as additional genes (NCOR1, TOM1L2, and PMP22) from the 17p11.2 amplicon, in 155 osteosarcomas from a prospective collection of tumors with corresponding clinical data. Univariate and multivariate analyses were performed to assess differences in survival between groups. RESULTS. Amplification of COPS3, detected in 31% of the osteosarcomas, was strongly associated with large tumor size (P = .0009), but was not associated with age at diagnosis, site, sex, and tumor necrosis. COPS3 amplification was significantly correlated with a shorter time to metastasis with an estimated hazard ratio (HR) of 1.61 (95% confidence interval [CI], 1.02,2.55) in univariate analysis (log-rank test, P = .042). However, in an a priori multivariate Cox model including the other clinical parameters, the HR for COPS3 amplification decreased to 1.32 (95% CI, 0.82,2.13, P = .25), mainly due to the strong correlation with tumor size. COPS3 amplification and P53 mutation frequently occurred in the same tumors, suggesting that these are not mutually exclusive events in osteosarcoma. Although not statistically significant, patients whose tumors exhibited both molecular alterations tended to be more likely to develop metastasis compared with patients with either COPS3 amplification or P53 mutation alone. CONCLUSIONS. COPS3 is the likely target of the 17p11.2 amplicon. COPS3 may function as an oncogene in osteosarcoma, and an increased copy number may lead to an unfavorable prognosis. Cancer 2007. © 2007 American Cancer Society. [source] | ||||||||||