Biomedical subjects

Abdissa Negassa

Publications and source records attributed to Abdissa Negassa.

13 recordsLinked to original sources

PubMed2006

The effect of omitted covariates on confidence interval and study power in binary outcome analysis: a simulation study.

BACKGROUND/OBJECTIVES: The consequence of omitted but balanced covariates on odds ratio point estimation is well-known in the literature. When exposure or intervention has a non-null effect on disease outcome, omitted covariates lead to underestimation of the effect of exposure or intervention. However, the effect of omitted covariates on confidence interval and study power is unknown. STUDY DESIGN AND SETTING: A simulation study is carried out to assess the effect of omitted covariates on confidence interval and study power for a plausible range of scenarios. Coverage probability and study power are assessed systematically over a range of study size, type of omitted covariate and magnitude of effect. A real-life example using a randomised experiment on flies' sexuality is provided. RESULTS: When a balanced covariate is omitted, coverage probability was lowered by 2.9-80%. Likewise study power was reduced by as much as 58%. The impact becomes substantial when the covariate is continuous, has large variability and has a larger effect than the effect of exposure or intervention. The result from a real-life example concurs with the simulation finding. CONCLUSION: Omitting an important balanced covariate lowers both coverage probability and study power. This implies the need for thoughtful consideration of important covariates at the design as well as the analysis stages of a study.

Animals↗

PubMed2006

Access to revascularization among patients with acute myocardial infarction in New York City--impact of hospital resources.

Timely revascularization can improve survival in patients with acute myocardial infarction. Identification of factors associated with increased use of revascularization in appropriate patients could improve outcomes. Using New York City hospital discharge records for 1988-1992 and 1998-2002, we determined revascularization rates for patients hospitalized with MI by neighborhood. Odds ratios for revascularization were estimated using a spatial model adjusting for neighborhood sociodemographic characteristics, while accounting for similarities in the rate of revascularization among geographically adjacent neighborhoods. Only 16 out of 112 New York City hospitals performed coronary revascularization. They were located in 14 of 41 neighborhoods. In general, patients living in neighborhoods with higher percentages of patients admitted to hospitals capable of revascularization service were more likely to be revascularized than those in neighborhoods with low percentages of patients admitted to hospitals with revascularization resources. This was true regardless of neighborhood availability of revascularization, after accounting for neighborhood socioeconomic characteristics and patients' clinical status. Revascularization rates in New York City increased from 1988-1992 to 1998-2002 in every neighborhood and as a whole from 103 to 326 per 1,000 hospitalized AMI patients. This increase was not explained by the addition of new revascularization services. Thus, in New York City, where only certain hospitals can perform revascularization, efficient delivery of patients to hospitals with these resources appears to increase the likelihood of revascularization performance among AMI patients without increasing the number of new hospitals capable of revascularization.

Health Services Accessibility↗

PubMed2005

Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the long-term clinical efficacy of inhaled iloprost as first-line vasodilator mono-therapy in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: Seventy-six IPAH patients were prospectively identified and treated with inhaled iloprost. Clinical, haemodynamic, and exercise parameters were obtained at baseline, after 3 and 12 months of therapy and yearly thereafter. Four endpoints were prospectively defined as follows: (i) death, (ii) transplantation, (iii) switch to intravenous (i.v.) therapy, or (iv) addition of or switch to other active oral therapy. During follow-up (535+/-61 days), 11 patients died, six were transplanted, 25 were switched to i.v. prostanoids, 16 received additional or other oral therapy, and 12 patients discontinued iloprost inhalation for other reasons. Event-free survival at 3, 12, 24, 36, 48, and 60 months was 81, 53, 29, 20, 17 and 13%, respectively. Among haemodynamic and exercise parameters, mixed venous oxygen saturation (P<0.001), right atrial pressure (P<0.001), and peak oxygen uptake (P=0.002) were associated with event-free survival. CONCLUSION: In this study, only a minority of patients could be stabilized with inhaled iloprost mono-therapy during a follow-up period of up to 5 years. In the presence of multiple treatment options, chronic iloprost inhalation as mono-therapy appears to have a limited role.

Administration, Inhalation↗

PubMed2005

Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus granulocyte-macrophage colony stimulating factor (GM-CSF) in non-Hodgkin's lymphoma.

PURPOSE: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). METHODS: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 microg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. RESULTS: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. CONCLUSIONS: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

Adult↗

PubMed2005

The Mayo Clinic Risk Score predicts in-hospital mortality following primary angioplasty.

BACKGROUND: The Mayo Clinic Risk Score (MCRS) is a validated numeric score that predicts outcome following primary percutaneous coronary intervention (PCI). PURPOSE: We evaluated the ability of MCRS to risk stratify patients undergoing primary angioplasty. METHODS: Patients undergoing primary angioplasty within 6 hours of the onset of chest pain in the New York State percutaneous coronary intervention reporting system (n = 3,005) had their MCRS calculated using predictive variables: age, presence of cardiogenic shock, renal failure, class III-IV congestive heart failure, left main coronary disease and multivessel coronary disease. All patients were presumed to have intra-coronary thrombus and undergoing an urgent/emergent procedure. Based on the MCRS, patients were classified into five risk categories: very low-risk (MCRS < 5), low risk (6-8), moderate (9-11), high (12-14) and very high risk (15-25). RESULTS: The mean age of the study population was 62 years, 70% were male; stents were used in 89% and glycoprotein IIb/IIIa antagonists in 72%. The prevalence of cardiogenic shock, multivessel disease and left main disease was higher in patients with MCRS > 12. Overall in-hospital mortality following primary angioplasty was 4.7%; it was 0% in the very low-risk category, 0.9% in the low-risk category, 3.2% in the moderate-risk category, 10.7% in the high-risk category, and 25.1% in the very high-risk category (p < 0.0001). The higher-risk MCRS category predicted increased risk even when 317 (10.5%) patients with cardiogenic shock were excluded from the analysis. The overall c-statistic for the prediction of in-hospital mortality by MCRS was 0.85. CONCLUSION: Increasing MCRS predicts in-hospital mortality following primary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2004

Phase II study of weekly docetaxel alone or in combination with trastuzumab in patients with metastatic breast cancer.

This study was designed to determine the efficacy and toxicity of weekly docetaxel in metastatic breast cancer when given alone (for HER2/neu negative disease) or with trastuzumab (for HER2/neu overexpressing disease). Patients with metastatic breast carcinoma received docetaxel given on 2 different schedules (group 1A, 33 mg/m2 weekly [n = 21]; group 1B, 40 mg/m2 weekly for 3 weeks with 1 week off [n = 14]). Patients with HER2/neu overexpressing disease also received trastuzumab 4 mg/kg on day 1, then 2 mg/kg on days 8 and 15 of each 28-day cycle (group 2). Fifty-two patients were treated with docetaxel alone (group 1A/B, n = 35) or in combination with trastuzumab (group 2, n = 17). Prior taxane therapy given every 3 weeks had been used for metastatic disease in 19 of 35 patients (54%) in group 1A/B and in 2 of 17 patients (12%) in group 2. The mean delivered dose intensity of docetaxel was 29 mg/m2 per week. Partial response occurred in 7 of 35 patients (21%; 95% exact binomial confidence interval [CI], 9%-38%) treated with docetaxel alone, including 3 of 19 taxane-pretreated patients (16%) and 4 of 16 taxane-naive patients (25%). Partial response occurred in 10 of 17 patients (59%; 95% CI, 34%-82%) treated with docetaxel/trastuzumab. The most common grade 3/4 toxicities, occurring in more than or equal to 10% of patients, included neutropenia (21%), pulmonary toxicity (12%), and hyperglycemia (10%). The median times to disease progression were 4.5 months (95% CI, 2.5-6.5 months) in the docetaxel group and 8.5 months (95% CI, 4.5-12.5 months) in the docetaxel/trastuzumab group. Weekly docetaxel/trastuzumab is an effective regimen for patients with HER2/neu overexpressing metastatic breast cancer. Weekly docetaxel may be effective in as many as 20% of patients who had progressive disease after treatment with taxanes given every 3 weeks.

Adenocarcinoma↗

PubMed2003

Modeling the time dependence of the association between human papillomavirus infection and cervical cancer precursor lesions.

The authors studied the time-dependent association between human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among women enrolled in a cohort study in Brazil (1993-2002), using repeated Papanicolaou cytologic examination and HPV testing by polymerase chain reaction. Through simulation with conceivable alternative cohort designs, they investigated different regression modeling approaches using time-varying covariates, time-varying hazard ratio functions, and repeated events to assess the effect of delay in lesion detection. Associations between HPV and early SIL were of high magnitude. The age-adjusted hazard ratios for the association between HPV at enrollment and low-grade SIL decreased gradually with time until 72 months for both oncogenic types of HPV (hazard ratio = 3.96, 95% confidence interval (CI): 2.5, 6.4) and nononcogenic types (hazard ratio = 2.37, 95% CI: 1.3, 4.3). The hazard ratio for incident high-grade SIL remained constant, ranging from 7.15 (95% CI: 2.0, 25.1) at 12 months to 6.26 (95% CI: 2.7, 14.5) at 72 months for oncogenic types of HPV. With oncogenic HPV as the time-dependent predictor variable, the hazard ratios for incident SIL and high-grade SIL events were 14.2 (95% CI: 8.7, 23.1) and 32.7 (95% CI: 8.4, 127.3), respectively. Investigators may underestimate the prognostic value of HPV detection using designs that rely on HPV ascertainment at a single time point. The waning in hazard ratios should be considered in the implementation of HPV testing-based screening programs.

Adult↗

PubMed2003

The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis.

Most human tumors display inactivation of the p53 and the p16(INK4)/pRb pathway. The Ink4a/alternative reading frame (ARF) locus encodes the p16(INK4a) and p14(ARF) (murine p19(ARF)) proteins. p16(INK4a) is deleted in 40-60% of breast cancer cell lines, and p16(INK4a) inactivation by DNA methylation occurs in < or =30% of human breast cancers. In mice genetically heterozygous for p16(INK4a) or Ink4a/Arf, predisposition to specific tumor types is enhanced. Ink4a/Arf(+/-) mice have increased E micro -Myc-induced lymphomagenesis and epidermal growth factor receptor-induced gliomagenesis. ErbB2 (epidermal growth factor receptor-related protein B2) is frequently overexpressed in human breast cancer and is sufficient for mammary tumorigenesis in vivo. We determined the role of heterozygosity at the Ink4a/Arf locus in ErbB2-induced mammary tumorigenesis. Compared with mouse mammary tumor virus-ErbB2 Ink4a/Arf(+/-) mice, mouse mammary tumor virus-ErbB2 Ink4a/Arf(wt) mammary tumors showed increased p16(INK4a), reduced Ki-67 expression, and reduced cyclin D1 protein but increased mammary tumor apoptosis with no significant change in the risk of developing mammary tumors. These studies demonstrate the contribution of Ink4a/Arf heterozygosity to tumor progression is tissue specific in vivo. In view of the important role of Ink4a/Arf in response to chemotherapy, these transgenic mice may provide a useful model for testing breast tumor therapies.

Adenocarcinoma↗

PubMed2003

Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study.

BACKGROUND: Weight loss in chronic heart failure is linked to impaired survival. We aimed to assess the frequency of weight loss in patients with this disease, whether the degree of weight loss predicts mortality, and whether weight loss can be prevented by angiotensin-converting-enzyme (ACE) inhibitors. METHODS: We investigated weight changes in 1929 patients from the SOLVD trial who had chronic heart failure, were free of oedema at baseline, and survived for at least 4 months after trial entry. Meanfollow-up was 35 months (SD 13). We analysed the effect of weight loss at cutpoints of 5%, 7.5%, 10%, 15% (a priori), and 6% (post hoc) to identify which one best predicted outcome. To validate results, we analysed data for 619 patients in the V-HeFT II trial. FINDINGS: 817 (42%) patients in the SOLVD trial had weight loss from baseline of 5% or more. At 8 months follow-up, all cutpoints for weight loss were significantly associated with impaired survival after adjustment for age, sex, New York Heart Association class, left ventricular ejection fraction, and treatment allocation. Weight loss of 6% or more at any time during follow-up was the strongest predictor of impaired survival (adjusted hazard ratio 2.10, 95% CI 1.77-2.49; p<0.0001). Patients on the ACE inhibitor enalapril had a lower hazard of 6% or more weight loss than did those not taking the drug (adjusted reduction 19%, p=0.0054). Results from analyses of V-HeFT II data lent support to our findings. INTERPRETATION: Weight loss occurs frequently in patients with chronic heart disease, its reversal is rare, and when present, it is independently linked to impaired survival. Weight loss of more than 6% should be used to define the presence of cachexia in patients with chronic heart failure. In chronic heart failure, treatment with an ACE inhibitor reduces the risk of weight loss.

Aged↗

PubMed2003

Statistical analysis of correlated data using generalized estimating equations: an orientation.

The method of generalized estimating equations (GEE) is often used to analyze longitudinal and other correlated response data, particularly if responses are binary. However, few descriptions of the method are accessible to epidemiologists. In this paper, the authors use small worked examples and one real data set, involving both binary and quantitative response data, to help end-users appreciate the essence of the method. The examples are simple enough to see the behind-the-scenes calculations and the essential role of weighted observations, and they allow nonstatisticians to imagine the calculations involved when the GEE method is applied to more complex multivariate data.

Body Height↗

PubMed2003

Phase II trial of infusional cyclophosphamide, idarubicin, and etoposide in poor prognosis non-Hodgkin's lymphoma.

The purpose of this study was to determine the complete response (CR) rate, failure-free survival (FFS), and overall survival (OS) of patients with poor-prognosis intermediate-grade non-Hodgkin's lymphoma (NHL) after treatment with cyclophosphamide, idarubicin, and etoposide given as a continuous intravenous infusion (CIVI) over 96 hours (infusional CIE), including patients with relapsed/refractory disease and patients with no prior therapy but at least two poor-risk features by the age-adjusted International Prognostic Index. Forty-two patients with previously untreated NHL (N = 24) or relapsed/refractory (N = 18) NHL received cyclophosphamide (200 mg/m2/d), idarubicin (2.5-3.0 mg/m2/d) and etoposide (60 mg/m2/d) given by a 96-hour CIVI every 3 weeks for a maximum of 8 cycles. All patients also received granulocyte-colony-stimulating factor. CR occurred in 10 of 24 patients (42%; 95% confidence intervals [CI] 22%, 62%) treated with CIE as first-line therapy, and in 3 of 18 patients (17%; 95% CI 20%, 32%) treated with CIE as second-line or greater therapy. One-year FFS and OS were 42% and 64%, respectively, in patients with no prior therapy, and 17% and 56% in patients with prior therapy. Severe (grade III) or life-threatening (grade IV) toxicity included leukopenia (59%), anemia (61%), thrombocytopenia (31%), and infection (10%). Two patients (4%) died due to treatment related infectious complications. It is unlikely that infusional CIE produces a CR rate more than about 60% in poor-risk patients with intermediate-grade NHL when used as first-line therapy, or more than about 30% in patients receiving the regimen as second-line therapy. Substitution of idarubicin for doxorubicin in this setting, therefore, is not associated with an improved response rate.

Adult↗

PubMed2002

Choice of clinical outcomes in randomized trials of heart failure therapies: disease-specific or overall outcomes?

BACKGROUND: There are different views regarding the appropriateness of using cause-specific events or all events as the primary outcome of clinical trials. METHODS: This is a methodologic essay in which we discuss the pros and cons of the 2 approaches and provide illustrative examples. RESULTS: Our preference is the use of cause-specific outcomes (as long as they can be classified with reasonable reproducibility and without bias) because they are more likely to be sensitive to change, less likely to lead to spurious conclusions by random variations in categories of outcomes that are unlikely to be affected by treatment, and relatively free from confounding. Overall benefit-risk ratios can be derived by examining the impact of treatment on various categories of outcomes and then developing a general judgment. Such an approach will also allow judgments to be made regarding generalizability of results across various groups of patients who are at differing risks for an event. CONCLUSIONS: In general, cause-specific outcomes sensitive to the effects of a treatment are to be preferred as the principal outcome in trials of heart failure, as long as they are biologically sensible and can be classified without bias. Other outcomes, not expected to be affected, should also be reported separately.

Bias↗

PubMed2002

Randomized phase II trial of embolization therapy versus chemoembolization therapy in previously treated patients with colorectal carcinoma metastatic to the liver.

Locoregional therapies are useful in treating patients with colorectal cancer metastatic to the liver. A prospective randomized phase II trial of hepatic artery embolization versus hepatic artery chemoembolization was conducted to evaluate the response rates and toxicities of these therapies in the second-line setting. Patients were required to have biopsy-proven adenocarcinoma of the colon or rectum metastatic to the liver, with the liver as the sole or predominant site of metastatic disease. All patients had measurable disease and had failed at least one prior systemic chemotherapy treatment for metastatic disease. Patients were randomized to receive either embolization therapy with polyvinyl alcohol foam (Ivalon) administered as a single agent or chemoembolization using polyvinyl alcohol foam mixed with 750 mg/m2 of 5-fluorouracil and 9 million units of interferon. Drugs and embolic material were administered via the hepatic artery as a slurry with polyvinyl alcohol foam. Fifty eligible patients were enrolled. There were 24 patients in the chemoembolization arm and 26 in the embolization arm. Sixty-four percent of patients in both treatment arms had the liver as the sole metastatic site. The most common National Cancer Institute common toxicity criteria grade 3/4 toxicities were diarrhea (17%) and hepatic toxicity (8%). There was 1 (4%) treatment-related mortality due to a hepatic abscess. Four patients (15.4%) treated with embolization had a partial response (PR), and 5 patients (20.8%) treated with chemoembolization had a PR. The median survival for all patients was 11 months (95% confidence interval [CI], 8-15 months). Survival in patients with extrahepatic disease was 8 months (95% CI, 6-10 months). Survival in patients with liver-only metastases was 15 months (95% CI, 10-17 months). Embolization of the liver as second-line therapy in patients with liver-predominant metastases is safe and effective. Median survivals are comparable to other second-line therapies

Adenocarcinoma↗