Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer.
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Humans↗
Biomedical subjects
Charles L Bennett
Publications and source records attributed to Charles L Bennett.
Literacy, self-efficacy, and HIV medication adherence.
OBJECTIVE: We examined the relationship between patient literacy level and self-reported HIV medication adherence, while estimating the mediating roles of treatment knowledge and self-efficacy on this relationship. METHODS: Structured patient interviews with a literacy assessment, supplemented by medical chart review, were conducted among 204 consecutive patients receiving care at infectious disease clinics in Shreveport, Louisiana and Chicago, Illinois. Literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), while the Patient Medication Adherence Questionnaire (PMAQ) was used to assess medication self-efficacy and adherence to antiretroviral regimens in the past 4 days. RESULTS: Approximately one-third of patients (30.4%) were less than 100% adherent to their regimen, and 31.4% had marginal to low literacy skills. In multivariate analyses, low literate patients were 3.3 times more likely to be non-adherent to their antiretroviral regimen (p < 0.001). Patients' self-efficacy, but not knowledge, mediated the impact of low literacy on medication adherence (AOR 7.4, 95% CI 2.7-12.5). CONCLUSION: While low literacy was a significant risk factor for improper adherence to HIV medication regimens in our study, self-efficacy mediated this relationship. PRACTICE IMPLICATIONS: Comprehensive intervention strategies that go beyond knowledge transfer may be needed to address self-efficacy among patients across all literacy levels to be successful in the management of difficult medication schedules.
Adult↗
Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) project.
Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) and granulocyte colony-stimulating factor (G-CSF) promote haematopoietic progenitor cell maturation. We reviewed the findings for healthy volunteers/donors who developed haematological malignancies following PEG-rHuMGDF or G-CSF administration. Information was reviewed for three of 538 volunteers who received PEG-rHuMGDF in clinical trials and two of 200 donors who underwent G-CSF mobilised stem cell harvesting procedures for sibling stem cell transplants. Mantle cell, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia were diagnosed 1-5 years after PEG-rHuMGDF exposure among three volunteers. For one patient, thrombocytopenia due to autoantibodies to PEG-rHuMGDF developed shortly after PEG-rHuMGDF administration and persisted until chemotherapy was administered. All three achieved complete remission, although one patient relapsed. Acute myeloid leukaemia was diagnosed 4 and 5 years after G-CSF mobilisation in two donors who underwent peripheral blood stem cell donation for sibling allogeneic haematopoietic stem cell transplantation. Following intensive chemotherapy, one died from acute leukaemia and the second is in complete remission. Controversy exists over the appropriateness of administering haematopoietic growth factors to healthy individuals. While a causal relationship with haematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive haematopoietic growth factors is needed.
Adult↗
Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project.
Gemtuzumab ozogamicin (GO) was approved for marketing in 2000 by the United States Food and Drug Administration (FDA) for older patients with relapsed acute myeloid leukemia (AML). Four months later, 14 phase II clinical trial participants who received novel GO-containing combination chemotherapy regimens developed an unexpected hepatic toxicity termed sinusoidal obstructive syndrome (SOS) or hepatic veno-occlusive disease (VOD). Investigators associated with the Research on Adverse Drug Events and Reports (RADAR) project reviewed safety reports for GO included in reports of clinical trials and observational studies, interim reports from an FDA mandated Prospective Observational Registry, and the Food and Drug Administration's Adverse Event Reporting System. Medline searches provided incidence estimates of GO-associated SOS and comparative rates of SOS without GO. SOS is characterized by hyperbilirubinemia, painful hepatomegaly, ascites, and sudden weight gain developing at a median of 10 days following GO administration for patients who did not undergo an allogeneic SCT procedure and 13 days following an allogeneic SCT for patients who had previously received GO. Among adult AML patients who received GO in clinical trials, SOS incidence was 3% at doses < or =6 mg/m(2) if administered as monotherapy or in combination with non-hepatotoxic agents versus 28% if administered with thioguanine and 15% when administered as monotherapy at a dose of 9 mg/m(2). Observational studies identified SOS rates between 15% and 40% if an SCT is performed within 3 months of GO administration. The FDA mandated Prospective Observational Registry of patients who receive care at 60 medical centers has identified GO-associated SOS rates of 14% if an SCT is performed and 9% otherwise. Caution is advised when administering GO in routine clinical practice, particularly if administered with other hepatotoxic agents, at doses and schedules more intensive than those approved by the FDA, or within 3 months of a SCT procedure.
Acute Disease↗
Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients.
This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.
Anemia, Hypochromic↗
When the risk of febrile neutropenia is 20%, prophylactic colony-stimulating factor use is clinically effective, but is it cost-effective?
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Antineoplastic Agents↗
2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.
PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). UPDATE METHODOLOGY: The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. RECOMMENDATIONS: The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.
Age Factors↗
Clinical features and correlates of gemcitabine-associated lung injury: findings from the RADAR project.
BACKGROUND: Gemcitabine is a commonly used chemotherapeutic agent structurally and pharmacologically similar to cytarabine. Recently, instances of severe gemcitabine-associated lung injury have been reported. Herein, investigators affiliated with the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program evaluated clinical characteristics of gemcitabine-associated severe acute lung injury from clinical trial reports, medical literature case reports, and spontaneous reports to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). METHODS: Clinical data were obtained by reviewing adverse event case reports for gemcitabine-associated lung injury as reported in the medical literature and in the FDA AERS database. Upper limit estimates of ADE rate were derived from review of published clinical trials reporting gemcitabine-associated lung injury rates of 10% or higher. RESULTS: A total of 178 reports of gencitabine-associated lung injury were identified; in AERS, there were 55 cases from clinical trials and 92 spontaneous reports. A comprehensive search revealed 31 medical literature reports. Clinical features of gemcitabine-associated lung injury included dyspnea, fever, pulmonary infiltrate, and cough with recognition of toxicity occurring after a median duration of 48 (range, 1-529) days after initiation of gemcitabine. The taxanes, docetaxel and paclitaxel, were frequently reported as coadministered therapies. Eleven Phase II or Phase III clinical trials with 317 patients identified gemcitabine-associated lung injury rates of greater than 10%, with the highest rates (22% and 42%) being observed in Phase III clinical trials where Hodgkin disease patients were treated with a regimen that included gemcitabine and bleomycin. CONCLUSIONS: High rates of gemcitabine-associated severe lung injury were observed when gemcitabine was combined with other therapies known to also cause lung injury. Physicians should have a high index of suspicion for this toxicity and report the relevant clinical findings to the FDA's AERS.
Antimetabolites, Antineoplastic↗
Cosmology from start to finish.
Cosmology is undergoing a revolution. With recent precise measurements of the cosmic microwave background radiation, large galaxy redshift surveys, better measurements of the expansion rate of the Universe and a host of other astrophysical observations, there is now a standard, highly constrained cosmological model. It is not a cosmology that was predicted. Unidentified dark particles dominate the matter content of our Universe, and mysteries surround the processes responsible for the accelerated expansion at its earliest moments (inflation?) and for its recent acceleration (dark energy?). New measurements must address the fundamental questions: what happened at the birth of the Universe, and what is its ultimate fate?
Journal Article↗
Local perspective of the impact of the HIPAA privacy rule on research.
BACKGROUND: The operational and economic impact of the Health Insurance Portability and Accountability Act (HIPAA) of 1996 was evaluated. The setting was a natural experiment which involved a single-site, clinical research study that was initiated before the enactment of HIPAA and subsequently modified to be compliant with the new policy. METHODS: A formative assessment was conducted of the recruitment process to a clinical trial evaluating the efficacy of an educational strategy to inform Veterans about the National Cancer Institute/Department of Veterans Affairs cosponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT). Personnel time and costs were determined based on weekly accrual for study periods before and after the implementation of HIPAA. Root cause analysis was used to assess the recruitment protocol and to identify areas for improvement. RESULTS: The implementation of HIPAA resulted in a 72.9% decrease in patient accrual (7.0 patients/wk vs. 1.9 patients/wk, P < 0.001), and a threefold increase in mean personnel time spent recruiting (4.1 hrs/patient vs. 14.1 hrs/patient, P < 0.001) and mean recruitment costs (49 US dollars/patient vs. 169 US dollars/patient, P < 0.001). Upon review of the modified HIPAA-compliant protocol, revisions in the recruitment procedure were adopted. The revised protocol improved weekly accrual by 73% (1.9 patients/wk vs. 7.1 patients/wk, P < 0.001) and resulted in improvements in personnel time (5.4 hrs/patient) and recruitment costs (65 US dollars/patient). CONCLUSION: Enactment of HIPAA initially placed a considerable burden on research time and costs. Establishing HIPAA-compliant recruitment policies can overcome some of these obstacles, although recruitment costs and time are likely to be greater than those observed before HIPAA.
Confidentiality↗
Literacy, race, and PSA level among low-income men newly diagnosed with prostate cancer.
OBJECTIVES: Among men with newly diagnosed prostate cancer, prostate-specific antigen (PSA) levels are higher and the cancer stage more advanced for African Americans than for whites. An earlier study found that after adjustment for literacy, race was no longer a significant predictor of advanced stage at presentation. We investigated whether, after adjusting for literacy, race was a significant independent predictor of greater PSA levels among men with newly diagnosed prostate cancer. METHODS: Consecutive patients with newly diagnosed prostate cancer from four outpatient care facilities in Chicago were interviewed and given a literacy assessment (n = 308). The PSA level at diagnosis was obtained from the medical charts. Logistic regression models were used to identify predictors of high PSA levels (greater than 20 ng/mL) at presentation. RESULTS: African-American men were three times more likely to have low literacy skills (sixth grade or less: 22.9% versus 7.1%; P <0.001) than were white men. In turn, men with low literacy skills were more than twice as likely to have a PSA level greater than 20 ng/mL at diagnosis (33.3% versus 13.5%; P = 0.009). On multivariate analyses, significant predictors of high PSA levels included low literacy (adjusted odds ratio 2.5, 95% confidence interval 1.5 to 4.2) and older age (age 65 to 74 years, adjusted odds ratio 2.6, 95% confidence interval 2.1 to 3.1 versus older than 74 years, adjusted odds ratio 3.4, 95% confidence interval 1.8 to 6.6), but not African-American race. CONCLUSIONS: In the current era in which PSA testing is common, low literacy may be an important and potentially overlooked factor associated with higher PSA levels at prostate cancer diagnosis among African-American and white men.
Aged↗
Social stigma concerns and HIV medication adherence.
The threat of social stigma may prevent people living with HIV from revealing their status to others and serve as a barrier to HIV treatment adherence. We evaluated the effect of such concerns on self-reported treatment adherence using a short, three-item measure among 204 people living with HIV. Overall, the mean age of participants was 40.1 years, 45% were African American, and 80% were male. People with high HIV stigma concerns were 2.5 times less likely to define and interpret the meaning of CD4 count correctly and 3.3 times more likely to be nonadherent to their medication regimen than those with low concerns. Concern over revealing HIV status was the only statistically significant, independent predictor of adherence in multivariate analysis. Clinical care directed to individuals living with HIV should therefore include considerations for patient sensitivity to social stigma, such as modifications to medication schedules and referrals for counseling prior to enrollment in antiretroviral therapies.
Adult↗
Low literacy impairs comprehension of prescription drug warning labels.
BACKGROUND: Adverse events resulting from medication error are a serious concern. Patients' literacy and their ability to understand medication information are increasingly seen as a safety issue. OBJECTIVE: To examine whether adult patients receiving primary care services at a public hospital clinic were able to correctly interpret commonly used prescription medication warning labels. DESIGN: In-person structured interviews with literacy assessment. SETTING: Public hospital, primary care clinic. PARTICIPANTS: A total of 251 adult patients waiting for an appointment at the Louisiana State University Health Sciences Center in Shreveport (LSUHSC-S) Primary Care Clinic. MEASUREMENTS: Correct interpretation, as determined by expert panel review of patients' verbatim responses, for each of 8 commonly used prescription medication warning labels. RESULTS: Approximately one-third of patients (n=74) were reading at or below the 6th-grade level (low literacy). Patient comprehension of warning labels was associated with one's literacy level. Multistep instructions proved difficult for patients across all literacy levels. After controlling for relevant potential confounding variables, patients with low literacy were 3.4 times less likely to interpret prescription medication warning labels correctly (95% confidence interval: 2.3 to 4.9). CONCLUSIONS: Patients with low literacy had difficulty understanding prescription medication warning labels. Patients of all literacy levels had better understanding of warning labels that contained single-step versus multiple-step instructions. Warning labels should be developed with consumer participation, especially with lower literate populations, to ensure comprehension of short, concise messages created with familiar words and recognizable icons.
Adolescent↗
Venous thromboembolic disease. Clinical practice guidelines in oncology.
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Female↗
Reducing adverse drug events in the outpatient chemotherapy setting: attention must be paid.
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Antineoplastic Agents↗
Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project.
OBJECTIVES: We undertook the review of all available cases of hypersensitivity reactions after placement of a drug-eluting stent (DES) and classified potential causes. BACKGROUND: Six months after the approval of the first DES, the Food and Drug Administration (FDA) reported 50 hypersensitivity reactions after stent placement but later concluded these were due to concomitantly prescribed medications such as clopidogrel. Nevertheless, the FDA continued to receive reports of hypersensitivity. METHODS: Reports available from April 2003 through December 2004 for hypersensitivity-like reactions associated with the sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) and paclitaxel-eluting stent (TAXUS, Boston Scientific Corp., Natick, Massachusetts) were reviewed. Sources of reports included the FDA's adverse-device-event database, the published literature, and investigators from the Research on Adverse Drug/Device events And Reports (RADAR) project. Causality was assessed using standardized World Health Organization criteria. RESULTS: Of 5,783 reports identified for the DES in the FDA database, 262 unique events included hypersensitivity symptoms. Of these reports, 2 were certainly and 39 unlikely caused by clopidogrel and 1 was certainly, 9 probably, and 13 unlikely caused by the DES. From all sources, we identified 17 distinct cases that were probably or certainly caused by the stent, of which 9 had symptoms that lasted longer than four weeks. Four autopsies confirmed intrastent eosinophilic inflammation, thrombosis, and lack of intimal healing. CONCLUSIONS: The FDA reports and autopsy findings suggest that DES may be a cause of systemic and intrastent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death.
Coronary Vessels↗
Caveat medicus: consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs.
In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide.
Antineoplastic Agents↗
Costs and cost effectiveness of a health care provider-directed intervention to promote colorectal cancer screening among Veterans.
PURPOSE: Colorectal cancer screening is underused, particularly in the Veterans Affairs (VA) population. In a randomized controlled trial, a health care provider-directed intervention that offered quarterly feedback to physicians on their patients' colorectal cancer screening rates led to a 9% increase in colorectal cancer screening rates among veterans. The objective of this secondary analysis was to assess the cost effectiveness of the colorectal cancer screening promotion intervention. METHODS: Providers in the intervention arm attended an educational workshop on colorectal cancer screening and received confidential feedback on individual and group-specific colorectal cancer screening rates. The primary end point was completion of colorectal cancer screening tests. Sensitivity analyses investigated cost-effectiveness estimates varying the data collection methods, costs of labor and technology, and the effectiveness of the intervention. RESULTS: Rates of colorectal cancer screening for the intervention versus control arms were 41.3% v 32.4%, respectively (P < .05). The incremental cost-effectiveness ratio was dollar 978 per additional veteran screened based on feedback reports generated from manual review of records. However, if feedback reports could be generated from information technology systems, sensitivity analyses indicate that the cost-effectiveness estimate would decrease to dollar 196 per additional veteran screened. CONCLUSION: An intervention based on quarterly feedback reports to physicians improved colorectal cancer screening rates at a VA medical center. This intervention would be cost effective if relevant data could be generated by existing information technology systems. Our findings may have broad applicability because a 2005 Medicare initiative will provide the VA electronic medical record system as a free benefit to all US physicians.
Aged↗