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ABSTRACT: Left atrial (LA) enlargement, left ventricular (LV) diastolic dysfunction, and increased arterial stiffness are all associated with adverse cardiovascular outcomes. The rate, magnitude, and concordance of modifiability of these risk markers have not been well characterized. Twenty-one patients (mean age 69 +/- 8 years; 52% women) with isolated diastolic dysfunction and indexed LA volumes > or =32 ml/m(2) were randomly assigned to receive either quinapril at a target dose of 60 mg/day or matching placebo for 12 months. Echocardiographic maximum LA volume and LV diastolic function and arterial stiffness by the augmentation index were measured at baseline and 6 and 12 months. Analysis was based on intention to treat. Baseline characteristics were comparable between the treatment (n = 9) and placebo (n = 12) groups. The mean reduction in LA volume of 4.2 +/- 7.8 ml/m(2) in the quinapril group was significant (p = 0.01) compared with the increase in LA volume in the placebo group (5.5 +/- 8.1 ml/m(2)). This represents a relative improvement of 9.7 ml/m(2). Change in LV filling pressure in terms of E/e' and diastolic function grade did not reach significance. A reduction in the augmentation index was associated with a decrease in indexed LA volume (odds ratio 11, p = 0.046), independent of changes in systolic blood pressure. In conclusion, LA structural remodeling appeared reversible with quinapril, which occurred in parallel with an improvement in arterial stiffness but independent of blood pressure changes.
The American Journal of Cardiology 03/2006; 97(6):916-20. · 3.37 Impact Factor
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ABSTRACT: Malignant phyllodes tumor (MPT) is a rare but aggressive breast malignancy. The aim of this study was to evaluate parameters that influence outcome in patients with MPT.
Fifty women were diagnosed with MPT of the breast and treated between August 1971 and July 2000. All medical records were reviewed retrospectively. The Cox regression model was used for multivariate analysis.
Tumors were classified as borderline (6%), low grade (32%), or high grade (62%). The median patient age was 46 years (range, 14-77 years). The median tumor diameter was 3.5 cm (range, 1.5-18 cm). Twenty-two patients had wide local excision (WLE), and 28 patients had mastectomy. The median follow-up was 91 months (range, 12-360 months). Local recurrence (LR) occurred in 16 patients (32%) an average of 26 months after surgery (median, 17 months; range, 3-72 months). Distant metastasis occurred in 13 patients (26%) at an average of 53.4 months (median, 36 months; range, 4-177 months). Sixteen (32%) patients have died of their disease. LR was significantly increased with stromal overgrowth (P < .0001), large tumor size (P = .0177), and surgical margins <1 cm (P = .0120), but not with WLE (P = .5099). Stromal overgrowth was the only independent variable predictive of systemic metastasis (P < .0001) and patient survival (P < .0001).
Stromal overgrowth in MPT carries a grave prognosis. Close surgical margins and large tumor size, but not type of operation, significantly increased LR. Either WLE with adequate margins or mastectomy is an appropriate treatment for patients with MPT.
Annals of Surgical Oncology 11/2004; 11(11):1011-7. · 4.17 Impact Factor
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ABSTRACT: The toxicity profile of fluorouracil (5-FU)-based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m(2) has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken.
Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher's exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression.
The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P <.0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes.
This study confirms an earlier finding that women receiving 5-FU-based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU-based chemotherapy for women should be lower than that for men.
Journal of Clinical Oncology 03/2002; 20(6):1491-8. · 18.37 Impact Factor
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Aminah Jatoi,
Marisa Tria Tirona, Steven S Cha,
Steven R Alberts,
Kendrith M Rowland,
Roscoe F Morton,
Suresh Nair,
Carl G Kardinal,
Philip J Stella,
James A Mailliard,
Daniel Sargen,
Richard M Goldberg
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ABSTRACT: The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination.
Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals.
The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo.
The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.
International Journal of Gastrointestinal Cancer 02/2002; 32(2-3):115-23.
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ABSTRACT: Several methods are available for the design of phase II clinical trials with binary endpoints. A primary assumption for most methods is that observations on the endpoint of interest are uncorrelated; however, this assumption is violated if an individual patient provides more than one observation on the endpoint of interest. In such cases, one solution is to use a summary measure for each patient; an alternative solution is to perform an observation-specific analysis using a technique that properly accounts for the correlation. In this paper, we investigate the effect that ignoring correlated observations can have on the design properties of the typical phase II clinical trial. In cases in which an observation-specific analysis is desirable, we propose a simple method that adjusts a standard one- or two-stage phase II design to account for loss of information due to correlated observations. Simulations demonstrate that the method ensures that type I and type II error rate design requirements are met even in the presence of strong correlation. We develop the method in the context of phase II oncology trials, but the method applies readily to other clinical areas in which multiple responses per patient are of interest. Control Clin Trials 1999;20:242–252
Controlled Clinical Trials 07/1999;
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ABSTRACT: Telemedicine options for symptom assessment include both telephonic means (call centers) and Internet sites. Although symptom assessment call centers have been available for decades, symptom assessment over the Internet is relatively new. It is not well known what types of symptoms Internet users are seeking assessment for and whether extant telephone triage algorithms would be applicable to Internet users.
Symptom assessments on a heavily used Internet site (MayoClinic.com) were compared with symptom calls to a U.S. call center (Ask Mayo Clinic).
Internet users sought symptom assessments about adult symptoms 13 times more often than children's symptoms. In contrast, over the telephone, adult symptoms were addressed 2.1 times more frequently than children's symptoms. Despite the differences in frequencies of adult and child symptom assessments, users of the Internet and telephone callers asked about specific symptoms with similar relative frequencies. Analysis of 20 adult symptom types shared by the Web and call center revealed that by excluding only 2 assessments (nasal symptoms and leg pain) the remaining 18 showed a significant correlation in counts of use (r(2) = 0.68, p < 0.001 for linear trend).
Internet users have symptoms assessed in similar proportions to callers, with a few exceptions. Compared with callers, Web users are much more likely looking for information about adult symptoms. Callers are proportionally asking more about acute symptoms, whereas Internet users appear more interested in symptom assessment of chronic conditions.
Telemedicine and e-Health 17(1):19-24. · 1.42 Impact Factor
