Yinong Young-Xu

Chemotherapy use among Medicare beneficiaries at the end of life

Context Some worry that physicians prescribe chemotherapy for patients with cancer at the end of life even when treatment is unlikely to prolong life or palliate symptoms. Contribution Among the study sample of Medicare beneficiaries who died of cancer in 1996, the proportions that received chemotherapy were about 30%, 20%, and 10% in the last 6, 3, and 1 months of life. Chemotherapy use was similar for types of cancer that usually respond to chemotherapy and those that do not. Implications During the last 6 months of life, many Medicare beneficiaries with cancer receive chemotherapy, regardless of the type of cancer they have. Unfortunately, this study does not tell us why. The Editors Many people are concerned that patients dying of cancer are frequently overtreated with chemotherapy (1-3). Indeed, some critics contend that oncologists prey on their patients vulnerability, imply that chemotherapy is the vehicle of hope, and press patients to try it before reconciling themselves to death (4). As one managed care executive claimed: My case managers are coming to me and saying that about half my patients are dying within 2 weeks of their last chemotherapy course. So where was the oncologist saying, its time for palliative care? Instead [patients] continue to get treated, and treated, and treated (5). Oncologists respond that they use chemotherapy prudently only when it is likely to extend life or relieve symptoms and that it is terminally ill patients and their families who demand treatment. Although there are some data on treatment of patients with metastatic cancer, data on how frequently patients with cancer receive chemotherapy in the months before death are lacking (6). Furthermore, there are no data on whether chemotherapy is used appropriately for cancer that responds to chemotherapy or for cancer for which chemotherapy is proven to relieve symptoms but not cancer unresponsive to chemotherapy. To provide such data, we examined the use of chemotherapy among Massachusetts and California Medicare beneficiaries who died of cancer. Methods Data Sources We obtained Medicare denominator (Medicare Provider Analysis and Review), outpatient, and carrier files from the Centers for Medicare & Medicaid Services (CMS); death certificate information from Massachusetts; and a random 5% sample of Medicare beneficiaries in California. Identifying the Study Sample We studied fully entitled, fee-for-service Medicare beneficiaries in Massachusetts and California who died in 1996, were at least 66 years of age at death, and were not enrolled in Medicares End Stage Renal Disease program. We merged CMSs denominator files with each states 1996 death certificate files and selected decedents whose underlying cause of death was cancer. Among 42 452 decedents in Massachusetts, 7919 died of cancer and met all other eligibility criteria. In California, Medicares 5% research sample encompassed 4715 decedents, including 956 study-eligible cancer decedents. Identifying Chemotherapy Use Chemotherapy was identified from claims in the inpatient, outpatient, or carrier Medicare files. Identifying codes were intravenous chemotherapy agents (Healthcare Common Procedure Coding System [HCPCS] codes 964xx, 965xx, and J9000 to 9999); chemotherapy administration (International Classification of Diseases, Ninth Revision [ICD-9], code 99.25, HCPCS codes Q0083 to Q0085); and medical evaluation for chemotherapy (ICD-9 codes V58.1, V66.2, and V67.2). Thus, we captured both hospital- and nonhospital-based chemotherapy administration, but could not capture (nonreimbursed) oral chemotherapeutic agents. We identified chemotherapy use for decedents in the six 30-day periods preceding death. Statistical Analysis Results are stated as percentages or means and standard deviations within groups with a reported denominator. Differences discussed are all statistically significant at a P value less than 0.05. Similarity statements are subjective assessments regarding clinical importance of magnitudes, not statistical tests. Statistical analyses were conducted by using SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Source This project was funded by the Department of Clinical Bioethics, Clinical Center, and National Institute of Aging, National Institutes of Health, which have no financial or other interests in the outcome. One author from the Department of Clinical Bioethics contributed to study design, conduct, and reporting. Results Frequency of Chemotherapy in the Last Months of Life In 1996, 33% of Medicare cancer decedents in Massachusetts received chemotherapy in the last 6 months of life, 23% in the last 3 months of life, and 9% in the last month of life (Table 1). In California, the percentages were 26%, 20%, and 9%, respectively. Although chemotherapy use during the last 6 and 3 months is more common in Massachusetts than in California (33% vs. 26% [P < 0.001]; 23% vs. 20% [P = 0.036], respectively), chemotherapy use in the last month of life is similar for the two states (9% vs. 9%; P > 0.2). Table 1. Characteristics of Cancer Decedents in Massachusetts and California by Receipt of Chemotherapy in the Last 6 Months of Life Table 1 shows the proportion of patients with each type of cancer who received chemotherapy in the last months of life. Patients who died of hematologic malignant conditions received chemotherapy most frequently. In both states, patients with breast, colon, or ovarian cancer, which tend to be more responsive to chemotherapy, received chemotherapy about as often as patients with less responsive tumors, such as pancreatic, hepatocellular, or renal-cell cancer or melanoma. None of the patients dying of melanoma or renal-cell cancer in Massachusetts received interferon- in the last 3 months of life. In both states, chemotherapy use decreases significantly with increasing age (Table 1). The use of chemotherapy is two to three times greater for Massachusetts patients 65 to 74 years of age than for patients 85 years of age and older and more than four times higher for the youngest versus oldest age groups in California (Massachusetts: 44% [65 to 74 years of age], 31% [75 to 84 years of age], 16% [ 85 years of age] [P < 0.001 for trend]; California: 39% [65 to 74 years of age], 25% [75 to 84 years of age], 8% [ 85 years of age] [P < 0.001 for trend]). This decrease in chemotherapy use by age was seen across cancer types and for both men and women (Appendix Table). Duration of Chemotherapy in the Last Months of Life Among Massachusetts patients receiving chemotherapy in the last 6 months of life, 41% received no more than 1 month of chemotherapy, 36% received 1 to 3 months of chemotherapy, and 23% received more than 3 months of chemotherapy (Table 2). Mean duration of chemotherapy use was somewhat shorter for men than women (2.2 months for men vs. 2.5 months for women; P = 0.003), and decreased significantly with age (2.5 months for patients 65 to 74 years of age, 2.3 months for patients 75 to 84 years of age, and 1.9 months for patients 85 years of age; P < 0.001 for trend). Only about one third of patients with breast, colon, or ovarian cancer received chemotherapy for 1 month or less; in contrast, half or more of patients with pancreatic, hepatocellular, or renal-cell cancer or melanoma received chemotherapy for 1 month or less (Table 2). Table 2. Massachusetts Cancer Decedents Receiving Chemotherapy in the Last 6 Months of Life and Duration of Chemotherapy Discussion This study examined chemotherapy use for Medicare cancer decedents in Massachusetts and California in their final months of life. Overall, more than one quarter of patients received chemotherapy in the last 6 months of life and more than 20% received chemotherapy in the last 3 months of life. Furthermore, because of the significantly greater use of chemotherapy in the last months of life at younger ages, chemotherapy use is likely to be even higher among all cancer decedents. Nevertheless, these data suggest that the claim that half of patients dying of cancer received chemotherapy within the last few weeks of life is exaggerated (5). Even among patients with hematologic malignant conditions, fewer than 20% received chemotherapy in their last month of life. Patients with pancreatic, hepatocellular, or renal-cell cancer or melanoma, which tend to be unresponsive to chemotherapy, were just as likely to receive chemotherapy in the last 6 months of life as patients with breast, colon, or ovarian cancer, which tend to be responsive to chemotherapy (7, 8). However, decedents with cancer unresponsive to chemotherapy were somewhat more likely to have only a short course of therapy. These findings suggest some selectivity in chemotherapy use at the end of life on the basis of the cancers responsiveness to chemotherapy. It is possible that after one therapy cycle, many patients and oncologists are convinced by ineffectiveness or the side effects to stop treatment for cancer unresponsive to chemotherapy. Nevertheless, many patients receiving chemotherapy for unresponsive cancer, such as pancreatic and hepatocellular cancer, received chemotherapy during 4 or more of the final 6 months of life. Although phase II data showing greater than 20% tumor responsiveness to chemotherapy can be cited for almost any cancer, most studies to date with single-agent or combination chemotherapy have shown little impact on quality of life or survival of the tumors typically classified as unresponsive (7, 8). Many reasons may explain chemotherapy use at the end of life. Desperate patients and families may demand a trial to see whether chemotherapy might shrink the tumor; indeed, patients with cancer are often willing to endure substantial side effects for small prolongations in life (9, 10). Lacking an established relationship and confronting an emotionally distraught patient and family, oncologists may provide one cycle of chemotherapy while the patient and

Racial and Ethnic Differences in End-Of-Life Costs: Why Do Minorities Cost More Than Whites?

BACKGROUNDnRacial and ethnic minorities generally receive fewer medical interventions than whites, but racial and ethnic patterns in Medicare expenditures and interventions may be quite different at lifes end.nnnMETHODSnBased on a random, stratified sample of Medicare decedents (N = 158 780) in 2001, we used regression to relate differences in age, sex, cause of death, total morbidity burden, geography, life-sustaining interventions (eg, ventilators), and hospice to racial and ethnic differences in Medicare expenditures in the last 6 months of life.nnnRESULTSnIn the final 6 months of life, costs for whites average

Long-term statin use and psychological well-being

20,166; blacks,

Systematic Review and Meta-Analysis of the Tolerability and Hepatotoxicity of Antifungals in Empirical and Definitive Therapy for Invasive Fungal Infection

26,704 (32% more); and Hispanics,

Pooling overdispersed binomial data to estimate event rate

31,702 (57% more). Similar differences exist within sexes, age groups, all causes of death, all sites of death, and within similar geographic areas. Differences in age, sex, cause of death, total morbidity burden, geography, socioeconomic status, and hospice use account for 53% and 63% of the higher costs for blacks and Hispanics, respectively. While whites use hospice most frequently (whites, 26%; blacks, 20%; and Hispanics, 23%), racial and ethnic differences in end-of-life expenditures are affected only minimally. However, fully 85% of the observed higher costs for nonwhites are accounted for after additionally modeling their greater end-of-life use of the intensive care unit and various intensive procedures (such as, gastrostomies, used by 10.5% of blacks, 9.1% of Hispanics, and 4.1% of whites).nnnCONCLUSIONSnAt lifes end, black and Hispanic decedents have substantially higher costs than whites. More than half of these cost differences are related to geographic, sociodemographic, and morbidity differences. Strikingly greater use of life-sustaining interventions accounts for most of the rest.

The safety and efficacy of gefitinib versus platinum-based doublets chemotherapy as the first-line treatment for advanced non-small-cell lung cancer patients in East Asia: A meta-analysis

OBJECTIVESnWe sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD).nnnBACKGROUNDnPrevious studies have suggested associations between cholesterol lowering and psychological well-being.nnnMETHODSnStudy subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores.nnnRESULTSnStudy subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs cholesterol-lowering effects.nnnCONCLUSIONSnLong-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility.

Long-term statin use and psychological well-being in the elderly

ABSTRACT To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.

Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease.

BackgroundThe beta-binomial model is one of the methods that can be used to validly combine event rates from overdispersed binomial data. Our objective is to provide a full description of this method and to update and broaden its applications in clinical and public health research.MethodsWe describe the statistical theories behind the beta-binomial model and the associated estimation methods. We supply information about statistical software that can provide beta-binomial estimations. Using a published example, we illustrate the application of the beta-binomial model when pooling overdispersed binomial data.ResultsIn an example regarding the safety of oral antifungal treatments, we had 41 treatment arms with event rates varying from 0% to 13.89%. Using the beta-binomial model, we obtained a summary event rate of 3.44% with a standard error of 0.59%. The parameters of the beta-binomial model took the values of 1.24 for alpha and 34.73 for beta.ConclusionThe beta-binomial model can provide a robust estimate for the summary event rate by pooling overdispersed binomial data from different studies. The explanation of the method and the demonstration of its applications should help researchers incorporate the beta-binomial method as they aggregate probabilities of events from heterogeneous studies.

Discrepancies in the Use of Medications: Their Extent and Predictors in an Outpatient Practice

BACKGROUNDnTo evaluate the risk/benefit profiles of gefitinib in comparison with platinum-based doublets chemotherapy as a first-line treatment for chemonaïve patients with advanced non-small-cell lung cancer in East Asia.nnnMETHODSnWe searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov to identify randomized and non-randomized phase II or III clinical trials of gefitinib or chemotherapy treatment in East Asian patients published before 4/30/2007. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Treatment arms with gefitinib 250mg/day and platinum-based doublets chemotherapy irrespective of dosage and schedule were combined to calculate the pooled estimates for efficacy and safety outcomes of interest.nnnRESULTSnWe identified 7 gefitinib and 41 platinum-based doublets chemotherapy trials with nearly 3000 enrolled patients for planned comparison. The pooled response rate (95% confidence interval) to gefitinib for unselected chemonaïve population was 31% (23-38%), not substantially different from 34% (31-38%) reported by platinum-based doublets chemotherapy trials. Patients with certain characteristics were more likely to benefit from gefitinib treatment, with pooled response rates as high as 75% (60-90%) for patients with epidermal growth factor receptor (EGFR) exon 18-21 mutations; 56% (38-74%) for never smokers; 55% (41-69%) for female; and 43% (30-57%) for adenocarcinoma or bronchioalveolar carcinoma. Severe hematological adverse events related to gefitinib treatment were not observed in any of the included trials. However, the risks of severe liver and lung injury related to gefitinib treatment were both approximately 6%, significantly higher than 1% and 0.2% reported by platinum-based doublets chemotherapy trials.nnnCONCLUSIONnOur data suggest that one third of chemonaïve NSCLC patients in East Asia would respond to oral gefitinib monotherapy while 6% would develop severe liver and lung injury. Although patients with EGFR gene mutations, female gender, non-smokers, or adenocarcinoma were more likely to respond to gefitinib, further study with valid comparison groups are needed to identify the optimal treatment strategy in these subpopulations.

Place Of Death: U.S. Trends Since 1980

Background: The effect of long-term statin use on psychometric measures was studied in a cohort of elderly patients with coronary disease. Methods The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility as measured annually with the Kellner Symptom Questionnaire. The Generalized Estimating Equation and multiple logistic regression estimated the odds ratios (ORs) and 95% confidence intervals (Cl), to represent the association between statin use and nsk of abnormal depression, anxiety. and hostility scores. Results 606 study subjects (average age 67, 80% male) mean follow-up 4 years, maximum 7 years were followed. Comparing the 140 patients with continuous statin use and 231 who did not use cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR, 0.64; 95% Cl, 0.43 0.93), anxiety scores (OR, 0.62; 95% Cl, 0.43-0.90). and hostility scores (OR, 0.65; 95% Cl, 0.45-0.93) after adjustment for confounders. NO association was found when 219 patients with intermittent statin use and non-&tin cholesterol-lowering drug use were compared with 231 patients who did not use cholesterol-lowering drugs. The risk of an abnormal psychometric score decreased over time. The beneficial psychological effects of the statins appeared to be independent of its cholesterol-lowering effect. Conclusions Long-term statin use is associated with reduced risk of anxiety. depression, and hostility in the elderly. Methods. To assess the results of TT in older patients, we analyzed the In-hospital, 6month and 24-month mortality in a cohort of 516 consecutive patients admined to a CCU for a first-time ST-segment/LBBB AMI enrrolled in the PPRIMM75 (Pron6stico del PRimer lnfalto de Miocardio en Mayores de 75 adios) Registry according to the type of treatment received: no reperlusion (n=314). TT (n=118) or primary angioplasty (PA, ll=84). Results. Patients treated with TT were admined earlier (median: 3 vs. 5 hours), nwrs frequently in Killip class I (77% vs 65%) and had a higher LVEF than non-reperfused patients (all pc.01). Compared with patients treated with PA, those who received TT had a significantly lower proportion of diabetes (27% vs 45%), anterior infarcts (42% vs 57%), LVEF < 0.31 (10% vs 24%) and Killip class I (23% vs 46%). The crude in-hospital mortality was 33.8% in non-reperiused patients, 28.8% in those treated with TT and 29.8% with PA. After excluding patients arriving in shock, the figures were: 28%, 27.4% and 17.9% respectively. The graph shows the odds ratio of in-hospital mortality and the hazard ratios for 6. and 24-month mortality for reperfused patients compared with non-reperfused patients after adjustment for baseline differences. Conclusion. Thrombolytic therapy may be associated with an early increase in morlality in elderly patients with AMI, an effect not observed with PA.