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David Goldstein

Publications and source records attributed to David Goldstein.

At least 19 recordsLinked to original sources
PubMed2022

Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence.

Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC's recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.

Humans↗
PubMed2006

The controversial association of ABCB1 polymorphisms in refractory epilepsy: an analysis of multiple SNPs in an Irish population.

Controversy has surrounded the reported association of the single nucleotide polymorphism (SNP) C3435T of the ATP-binding cassette subfamily B member 1 (ABCB1, MDR1) gene, with refractory epilepsy. Here we examine this question by: (1) attempting to replicate the original association, (2) assessing the association of other variants in high linkage disequilibrium (LD) with C3435T, and (3) evaluating and comparing our findings with other published studies. We defined drug-responsiveness as seizure freedom or a 50% or more reduction in seizure frequency in the preceding year. Drug resistance was defined as a less than 50% reduction in seizure frequency in the preceding year. We used a combination of map-based (tagging SNPs) and direct sequence-based methods allowing a comprehensive assessment of variation across the associated interval. Genotypic data on 8 SNPs was collected on 440 patients, of whom 242 were drug-responsive and 198 were drug-resistant. We were unable to observe the original association of drug-resistant epilepsy with C3435T, nor any association with other functional variants at SNP or haplotype level in the ABCB1 gene. Evaluation of other attempted replication studies suggest that if the original C3435T association is indeed real, it would appear highly sensitive to the phenotype used. Alternatively, the discrepant results of this and other association attempts may be indicative of the original report of the CC genotype at C3435T in ABCB1 being a false positive finding. Variability in phenotypic descriptions in genetic association studies may partly explain the inconsistency of attempted replications.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Fatigue states after cancer treatment occur both in association with, and independent of, mood disorder: a longitudinal study.

BACKGROUND: Persistent fatigue is recognised as one of the most common, ongoing symptoms reported by patients following cancer treatment and may have profound effects on the quality of life. However, recent cross-sectional studies also highlight the close relationship between cancer related fatigue (CRF) and diagnoses of depression or anxiety disorder. There is currently limited information about the relationships between these conditions over time. We sought to examine the longitudinal relationships between fatigue and mood disorder in women treated with adjuvant therapy for early stage breast cancer. METHODS: Women who had recently completed adjuvant therapy for Stage I or II breast cancer (n = 212) were sent a questionnaire with established case thresholds for clinically-significant fatigue and psychological disorder, as well as a questionnaire assessing disability. Potentially relevant variables linked to fatigue states, including age, treatment modality, menopausal status, and hematological indices were recorded. The illness outcomes were assessed over 48 months of follow-up. RESULTS: The 176 women who responded to the questionnaire (84%) had a mean age of 55 (range 24-83) years and had completed adjuvant treatment on average 10 (range 4.7-16.3) months previously. Radiotherapy had been administered, either alone (50% of women) or in combination with chemotherapy (36%). Responses from 87 women (48%) indicated a significant fatigue state (termed here post-cancer fatigue; PCF), and from 59 women (33%) responses indicated significant psychological distress. Thirty-four women (19%) were cases of fatigue alone (i.e. unaccompanied by psychological disorder), whereas 52 (30%) were cases of both disorders. Multivariate analysis did not reveal any association between demographic, clinical or laboratory variables, and caseness for PCF. Self-reported functional disability was significantly associated with fatigue. Follow-up at 24, 36 and 48 months revealed high rates of ongoing PCF in conjunction with psychological distress, despite falling rates of psychological distress alone and fatigue alone. CONCLUSION: Post-cancer fatigue was prevalent and sustained on follow-up. Concurrent psychological disorder was evident in the majority, but not all, cases of PCF and tended to be sustained over time. Further prospective cohort studies to define the longitudinal co-morbid relationships between fatigue, mood disorder, and ongoing disability after cancer treatment are indicated.

Adult↗
PubMed2006

Oxaliplatin and axonal Na+ channel function in vivo.

PURPOSE: The aim of the study was to investigate the pathophysiology of oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques that provide information about axonal ion channel function. EXPERIMENTAL DESIGN: Excitability studies were combined with standard nerve conduction studies and clinical assessment in 22 patients undergoing treatment with oxaliplatin. RESULTS: Excitability studies recorded before and immediately after oxaliplatin infusion for 89 treatment cycles revealed significant increases in refractoriness and relative refractory period postinfusion in all patients, consistent with an effect of oxaliplatin on axonal Na(+) channels. However, those patients that developed chronic neuropathy had significantly greater changes. Following cessation of oxaliplatin treatment, 41% of patients had persistent symptoms and nerve conduction abnormalities consistent with the development of chronic neuropathy. CONCLUSION: The present study provides evidence that oxaliplatin-induced neurotoxicity is mediated through an effect on axonal Na(+) channels. Clinical nerve excitability techniques may prove beneficial in monitoring for early signs of neurotoxicity and in the assessment of future prophylactic therapies.

Adult↗
PubMed2006

Primary pancreatic lymphoma--pancreatic tumours that are potentially curable without resection, a retrospective review of four cases.

BACKGROUND: Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. METHODS: Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. RESULTS: All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. CONCLUSION: Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes.

Aged↗
PubMed2006

Half of patients with obstructive sleep apnea have a higher NREM AHI than REM AHI.

BACKGROUND AND PURPOSE: To determine the percentage of sequential patients with obstructive sleep apnea with a higher non-rapid eye movement (NREM) apnea-hypopnea index (AHI) than rapid eye movement (REM) AHI and those with a higher REM AHI than NREM AHI, and to look for factors that might influence the AHI to be higher in one of these two groups versus the other and thus ascertain the factors that cause an AHI to be higher in NREM than REM. A high body mass index (BMI) and a supine body position are well known as exacerbating factors for obstructive sleep apnea (OSA). Males, as well as older individuals, are generally more predominantly affected with OSA than females. Usually OSA is worse in REM sleep than in NREM sleep, although this is not always true. METHODS: A retrospective study of sequential patients from one month's admission to a single sleep laboratory was conducted. We determined the age, sex, BMI, body position, duration of apnea, amount of time spent in REM and oxygen desaturation in patients who had a higher NREM AHI than REM AHI versus those who had a higher REM AHI than NREM AHI. To minimize variability, the sleep studies were scored by a single individual. RESULTS: A higher NREM AHI than REM AHI was found in 50% of the 66 patients with OSA. Males predominated in each group and there was no age difference between the groups. Although AHI for both groups tended to become higher with an increase in BMI, the BMI was not statistically different between the two experimental groups. OSA was worse in the supine position in both experimental groups consistent with previous literature. Percentage of time spent in REM or the duration of the apnea did not determine whether a patient fell into the NREM AHI>REM AHI group versus the REM AHI>NREM AHI. The severity of oxygen desaturation was not significantly different between the NREM AHI>REM AHI versus the REM AHI>NREM AHI group. However, when we combined and analyzed the two groups as a whole, the apneas were longer in REM, consistent with previous literature. CONCLUSIONS: Although it is well known that OSA is generally worse in REM sleep because of the degree of desaturation and duration of apnea, a higher NREM AHI than REM AHI is found in up to one half of individuals. Most of the usual predictors for severity of OSA as a whole did not discriminate these groups. Further work needs to be done to determine the factors that discriminate these two groups and thus make AHI higher in NREM than REM.

Adult↗
PubMed2006

The utility of videoconferencing to provide innovative delivery of psychological treatment for rural cancer patients: results of a pilot study.

The unmet psychological needs of rural cancer patients are numerous. Telepsychology is a novel and feasible option that may provide cost-savings and help overcome inequalities in access to specialists. This is the first known study of psychological treatment for people with cancer delivered entirely via videoconferencing. We hypothesized that a telepsychology service would improve rural cancer patients' anxiety and depression levels and quality of life, and would be an acceptable, satisfactory, and practical mode of service delivery. Twenty-five cancer patients attended an average of three sessions with a clinical psychologist providing brief cognitive-behavioral therapy. Questionnaires were completed at pre-, post-, and 1-month follow-up. Patients benefited in terms of anxiety (P=0.01) and quality of life (P=0.04). The service was both practical and acceptable. These preliminary positive results provide a firm basis to conduct a randomized controlled trial of face-to-face interaction vs. videoconferencing.

Adult↗
PubMed2006

Update on pharmacogenetics in epilepsy: a brief review.

Recent developments in the pharmacogenetics of antiepileptic drugs provide new prospects for predicting the efficacy of treatment and potential side-effects. Epilepsy is a common, serious, and treatable neurological disorder, yet current treatment is limited by high rates of adverse drug reactions and lack of complete seizure control in a significant proportion of patients. The disorder is especially suitable for pharmacogenetic investigation because treatment response can be quantified and side-effects can be assessed with validated measures. Additionally, there is substantial knowledge of the pharmacodynamics and kinetics of antiepileptic drugs, and some candidate genes implicated in the disorder have been identified. However, recent studies of the association of particular genes and their genetic variants with seizure control and adverse drug reactions have not provided unifying conclusions. This article reviews the published work and summarises the state of research in this area. Future directions for research and the application of this technology to the clinical practice of individualising treatment for epilepsy are discussed.

Anticonvulsants↗
PubMed2006

Toward cultural competence in cancer genetic counseling and genetics education: lessons learned from Chinese-Australians.

PURPOSE: In societies such as Australia with a strong multicultural makeup, culturally determined attitudes to genetics, testing, and counseling may be incompatible with current genetics service provision. METHODS: An ethnographic investigation using purposive sampling to increase subject diversity was used to explore the range of beliefs about kinship and inheritance using Chinese-Australians as a case. Participants comprised a sample of 15 Chinese-Australians who had been recruited through several community-based organizations. RESULTS: The level of acculturation does not correlate with holding beliefs about inheritance, kinship, and causes of hereditary cancer that are based on "Western" biomedical or traditional concepts. Mismatch between beliefs may exist within families that can impact participation in cancer genetic testing. Family history taking that underpins the surveillance, management, and referral to genetic counseling where there is a strong family history of breast, ovarian, or colorectal cancer can also be impacted unless recognition is made of the patrilineal concept of kinship prevalent in this Chinese-Australian community. CONCLUSION: This community-based study confirmed and validated views and beliefs on inheritance and kinship and inherited cancer attributed to senior family members by Chinese-Australians who attended cancer genetic counseling. Barriers to communication can occur where there may be incompatibility within the family between "Western" and traditional beliefs. The findings were used to develop strategies for culturally competent cancer genetic counseling with Australian-Chinese patients. These include nonjudgmental incorporation of their belief systems into the genetic counseling process and avoidance of stereotyping. They have also influenced the development of genetics education materials to optimize family history taking.

Adult↗
PubMed2006

An educational workshop program for rural practitioners to encourage best practice for delivery of systemic adjuvant therapy.

BACKGROUND: The Rural Systemic Adjuvant Therapy Project was initiated to encourage best practice in the treatment of women from rural areas who have breast cancer. METHOD: We developed an educational program, piloted it and conducted it in 5 regions. In a pre-evaluation/post-evaluation, we assessed participants' perceived knowledge about systemic adjuvant therapy. RESULTS: A statistically significant increase occurred in participants' reported knowledge about all program topics. Improved communication links with the local or visiting medical oncologist were planned. CONCLUSION: The workshop program was found to be a successful tool for delivering evidence-based information about the use of systemic adjuvant therapy.

Analysis of Variance↗
PubMed2006

Colorimetric evaluation of facial skin and free flap donor sites in various ethnic populations.

OBJECTIVE: To determine the optimal colour match for free tissue donor sites transferred to defects of the cheek and neck in a multicultural population. DESIGN: A prospective measurement of the colour of potential free flap donor sites and recipient sites in healthy volunteers. SETTING: A tertiary care academic health science centre. METHODS: Sixty-four healthy volunteers (Caucasian, black, South Asian, Southeast Asian) underwent noninvasive skin colour measurement of the cheek and neck, as well as a standard set of potential free tissue donor sites using a Minolta CR 300 (Konica-Minolta Canada; Markham, ON, Canada) chromameter. MAIN OUTCOME MEASURES: Measurement was done using derived colour measurements based on the Commission Internationale de l'Eclairage or International Commission on Light (CIE) L*a*b* tristimulus values. E* is a derived value of colour difference between sites using the L*a*b* measures. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Variations exist between optimal donor sites in individuals of different ethnic backgrounds. Mean E* values suggest that in Caucasians, Southeast Asians, and South Asians, the upper extremity and trapezius flaps most closely approximate the recipient sites. In blacks, the variation in mean E* values is small and a wide variety of flaps provide a colour match to the cheek and neck. Luminance values support the observations regarding E*. DISCUSSION: Wide variations exist between individuals of different ethnic backgrounds in terms of optimal donor sites for the best colour match to surgical defects of the cheek and neck. In Caucasians, it appears that upper extremity sites, including the forearm and lateral arm flaps, provide the best colour match. Similar observations can be made in South Asians and Southeast Asians, with upper extremity flaps providing the best colour match. In blacks, there does not seem to be much variation in colour across the commonly used donor site, and a larger panel of flaps will provide an appropriate colour match in this subset of patients.

Adult↗
PubMed2006

Morbidity and cost differences between free flap reconstruction and pedicled flap reconstruction in oral and oropharyngeal cancer: Matched control study.

BACKGROUND: To compare morbidity and cost in patients who underwent primary reconstruction with free tissue transfer with those with pectoralis major myocutaneous flap (PMMF) reconstructions after ablation of oral and oropharyngeal squamous cell carcinoma. METHODS: Over a 6-year period, 36 patients had PMMF reconstructions and 127 patients had a variety of free flap (FRF) reconstructions after oral and oropharyngeal cancer ablation. Correction for confounding patient and disease variables was performed by matching all PMMF patients to a randomly selected cohort of FRF patients for age, sex, International Union Against Cancer-American Joint Committee on Cancer T category, tumour subsite, and radiotherapy status. This resulted in two groups of 32 patients each, with the flap reconstruction being the only variable. The following outcome variables were analyzed: operative time; blood loss; admission length, including intensive care unit and coronary care unit stay; complications; secondary interventions; readmissions; and feeding status. Cumulative costs of nursing care, hospital supplies and charges, surgeon's fees, and anesthesiologist's fees were calculated. Statistical analysis applied the paired Student's t-test and the chi-square test. RESULTS: Of all morbidity parameters, only operative time was significantly longer for FRF (p < .0001). Analysis of other outcome variables and costs showed no statistically significant differences (p > .05). CONCLUSION: There is no evidence that morbidity and cost differ between the pedicled flap and free tissue transfer reconstruction strategies, other than lengthier operating room time for FRF.

Adult↗
PubMed2006

Addition of gabapentin to a modified FOLFOX regimen does not reduce oxaliplatin-induced neurotoxicity.

BACKGROUND: Sensory neurotoxicity is dose limiting for oxaliplatin, an effective drug in the treatment of colorectal cancer (CRC) and other malignancies. This study assessed the impact of gabapentin on oxaliplatin dose intensity and neurotoxicity. PATIENTS AND METHODS: Patients with previously untreated metastatic CRC were recruited sequentially to 2 cohorts: the first used a modified FOLFOX6 (fluorouracil/leucovorin/oxaliplatin) regimen alone with oxaliplatin 100 mg/m(2) every 2 weeks (mFOLFOX; n = 40), and the second included the addition of gabapentin (mFOLFOX+G; n = 41). Gabapentin commenced at 300 mg daily, increasing to a maximum of 600 mg 3 times daily to decrease neurotoxicity. RESULTS: Doses of gabapentin were increased in 31 of 41 patients, with 39% of patients receiving >or= 900 mg daily. The median relative dose intensity of oxaliplatin and requirement for dose reductions or delays because of neurotoxicity were similar in the 2 cohorts. There was no grade 4 neurotoxicity. Whereas grade 3 neurotoxicity was observed in 10% of patients treated with gabapentin versus 21% of patients treated with mFOLFOX alone, there was no statistically significant difference in the severity of neurotoxicity between the 2 cohorts (P = 0.89) or the time to recover from grade 2/3 neurotoxicity (P = 0.97). There were also no significant differences in nonneurologic toxicity or antitumor efficacy between the 2 cohorts. CONCLUSION: This study does not support a role for gabapentin in reducing the incidence or severity of oxaliplatin-induced sensory neurotoxicity.

Amines↗
PubMed2005

Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response--an AGITG study.

BACKGROUND: Malignant gastrointestinal stromal tumours (GISTs) are a rare subset of aggressive mesenchymal tumours specific to the gastrointestinal system. They are both locally aggressive and can metastasize. The aim of this analysis was to report on our experience of the utility of coincidence positron emission tomography (co-PET) based on an 18F-FDG gamma camera in assessing treatment response to imatinib using CT as the comparator and the final clinical outcome as the end point. METHODS: We compared the results of CT and PET scans as predictors of outcome in a consecutive series of patients treated at the Prince of Wales hospital. All patients had biopsy-proven malignant GIST and were on treatment with the targeted pharmacotherapeutic agent imatinib. The majority of the patients were receiving treatment as part of the randomized trial of the European Organization for Research and Treatment of Cancer, the Australian Gastrointestinal Trials Group and the Italian Sarcoma Group, comparing 400 with 800 mg (400 mg b.i.d.). The monitoring of tumour response was achieved by serial CT measurements according to the RECIST criteria. Concurrent 18F-FDG co-PET studies were performed within a mean of 2.8 days from the CT scan and were interpreted by a consensus panel of 2 nuclear medicine physicians. RESULTS: A total of 18 patients were recruited into the study, with a total of 74 lesions. There were 47 liver lesions, 31 of which were identified on the initial 18F-FDG co-PET scans (63%). There were 10 primary lesions (4 stomach, 4 duodenal, 2 small bowel), 9 of which were demonstrated on initial 18F-FDG co-PET examinations (90%). There were 17 extrahepatic metastatic sites, 15 of which were visualized on the initial 18F-FDG study (88%). Of the 18 patients, 8 showed concordant improvement on both CT and (18)F-FDG co-PET criteria. One patient showed concordant worsening and 1 was not FDG avid. Eight patients initially showed discordance. 18F-FDG co-PET studies demonstrated changes preceding CT findings in all 8 patients with subsequent concordant improvement. CONCLUSION: 18F-FDG co-PET is a useful modality to monitor treatment response to imatinib in patients with malignant GIST. Although there is a relatively reduced sensitivity when compared with CT for the detection of lesions especially in the liver, co-PET changes in several instances precede the changes on CT scanning. This modality has the potential to influence clinical decision making and should be considered as part of the standard care of patients on imatinib.

Antineoplastic Agents↗
PubMed2005

Interferon-alpha promotes the anti-proliferative effect of gefitinib (ZD 1839) on human colon cancer cell lines.

OBJECTIVE: Interferon-alpha (IFN alpha) treatment is associated with up-regulation of epidermal growth factor receptor (HER 1/EGFR) expression and marked growth inhibition of colon cancer cell lines in vitro. We aimed to determine the effect of combining IFN alpha and gefitinib on colon cancer cell line growth. METHODS: A panel of nine colon cancer cell lines were characterised for expression of HER 1/EGFR and then treated with gefitinib alone, or IFN alpha alone, or IFN alpha plus gefitinib, following a pre-treatment using vehicle or IFN alpha. Crystal violet staining and flow cytometry were used to assess cell proliferation and expression of HER 1/EGFR. The indexes and statistical assays were used to evaluate significant differences between treatment groups against vehicle control. RESULTS: All cell lines except SW 620 were HER 1/EGFR positive. IFN alpha treatment was associated with significant up-regulation of cell surface HER 1/EGFR expression in all HER 1/EGFR-positive cell lines except KM 12 SM. Concurrent treatment with IFN alpha and gefitinib, or IFN alpha pre-treatment followed by gefitinib, or IFN alpha pre-treatment followed by a combination of IFN alpha plus gefitinib, additively or supra-additively/synergistically enhanced the sensitivity of the seven HER 1/EGFR-up-regulated cell lines. CONCLUSION: IFN alpha improves the anti-proliferative effect of EGFR inhibition in colorectal cancer cell lines. This approach may have clinical implications for improving treatment based on targeting of HER 1/EGFR.

Analysis of Variance↗
PubMed2005

Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study.

PURPOSE: The aim of this study was to identify factors predicting initial and late resistance of GI stromal tumor (GIST) patients to imatinib and to document the dose-response relationship in the prognostic subgroups. This study is based on the European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group randomized trial comparing two doses of imatinib in advanced disease. PATIENTS AND METHODS: Initial resistance was defined as progression within 3 months of randomization, and late resistance was defined as progression beyond 3 months. Investigated cofactors include imatinib dose, age, sex, performance status, original disease site, site and size of lesions at trial entry, and baseline hematologic and biologic parameters. RESULTS: Initial resistance was recorded for 116 (12%) of 934 assessable patients and was independently predicted by the presence of lung and absence of liver metastases, low hemoglobin level, and high granulocyte count. Among 818 patients who were alive and progression free at 3 months, 347 subsequent progressions were recorded, and late resistance was independently predicted by high baseline granulocyte count, primary tumor outside of the stomach, large tumor size, and low initial imatinib dose. The impact of initial dose on late resistance was mainly significant in patients with a high baseline granulocyte count (> 5.10(9)/L) and in patients with tumors of GI origin outside of the stomach and small intestine. CONCLUSION: Our study identifies patients for whom initial and/or long-term treatment needs to be improved and patients who require a high initial dose. Correlation of these results with immunohistochemistry and molecular parameters may further help to understand the biologic mechanisms of resistance.

Adult↗
PubMed2005

Hemoglobin A1c measurements over nearly two decades: sustaining comparable values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications study.

BACKGROUND: Clinical trials require assays that provide consistent results during the course of a study. The hemoglobin A1c (HbA1c) assay, a measure of chronic glycemia, is critical to the study of diabetes control and complications. METHODS: The Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), required 20 years of consistent HbA1c results, measured by three different ion-exchange HPLC procedures. To maintain and document consistent HbA1c results measured in the DCCT and EDIC Central Biochemistry Laboratory, a backup laboratory used frozen hemolysates as long-term calibrators and a HPLC method with a single lot of Bio-Rex 70 resin. RESULTS: Over 20 years, long-term quality-control values have remained constant. Four studies of nondiabetic ranges produced nearly identical values [mean (SD), 5.1 (0.5)%, 4.9 (0.3)%, 5.0 (0.4)%, and 5.0 (0.3)%]. CONCLUSION: The overall consistency of the HbA1c assays during the 20-year course of the DCCT and EDIC has been critical in establishing the benefits of intensive therapy and in understanding the relationship between long-term glycemia and the development and progression of the complications of diabetes.

Chromatography, High Pressure Liquid↗