Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer.

PURPOSE: Patients with cancer are more likely to file for bankruptcy than the general population, but the impact of severe financial distress on health outcomes among patients with cancer is not known. METHODS: We linked Western Washington SEER Cancer Registry records with federal bankruptcy records for the region. By using propensity score matching to account for differences in several demographic and clinical factors between patients who did and did not file for bankruptcy, we then fit Cox proportional hazards models to examine the relationship between bankruptcy filing and survival. RESULTS: Between 1995 and 2009, 231,596 persons were diagnosed with cancer. Patients who filed for bankruptcy (n = 4,728) were more likely to be younger, female, and nonwhite, to have local- or regional- (v distant-) stage disease at diagnosis, and have received treatment. After propensity score matching, 3,841 patients remained in each group (bankruptcy v no bankruptcy). In the matched sample, mean age was 53.0 years, 54% were men, mean income was $49,000, and majorities were white (86%), married (60%), and urban (91%) and had local- or regional-stage disease at diagnosis (84%). Both groups received similar initial treatments. The adjusted hazard ratio for mortality among patients with cancer who filed for bankruptcy versus those who did not was 1.79 (95% CI, 1.64 to 1.96). Hazard ratios varied by cancer type: colorectal, prostate, and thyroid cancers had the highest hazard ratios. Excluding patients with distant-stage disease from the models did not have an effect on results. CONCLUSION: Severe financial distress requiring bankruptcy protection after cancer diagnosis appears to be a risk factor for mortality. Further research is needed to understand the process by which extreme financial distress influences survival after cancer diagnosis and to find strategies that could mitigate this risk.

Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis.

BACKGROUND: Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. AIM: To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. MATERIALS & METHODS: We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. RESULTS: The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. CONCLUSION: Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

Impact of prostate cancer on sexual relationships: a longitudinal perspective on intimate partners' experiences.

INTRODUCTION: In this prospective study of localized prostate cancer patients and their partners, we analyzed how partner issues evolve over time, focusing on satisfaction with care, influence of cancer treatment, and its impact on relationship with patient, cancer worry, and personal activities. AIMS: Our study aims were twofold: (i) to determine whether the impact of treatment on patients and partners moderate over time and (ii) if receiving surgery (i.e., radical prostatectomy) influences partner issues more than other treatments. METHODS: Patients newly diagnosed with localized prostate cancer and their female partners were recruited from three states to complete surveys by mail at three time points over 12 months. MAIN OUTCOME MEASURES: The four primary outcomes assessed in the partner analysis included satisfaction with treatment, cancer worry, and the influence of cancer and its treatment on their relationship (both general relationship and sexual relationship). RESULTS: This analysis included 88 patient-partner pairs. At 6 months, partners reported that cancer had a negative impact on their sexual relationship (39%--somewhat negative and 12%--very negative). At 12 months, this proportion increased substantially (42%--somewhat negative and 29%--very negative). Partners were significantly more likely to report that their sexual relationship was worse when the patient reported having surgery (P = 0.0045, odds ratio = 9.8025, 95% confidence interval 2.076-46.296). A minority of partners reported significant negative impacts in other areas involving their personal activities (16% at 6 months and 25% at 12 months) or work life (6% at 6 months, which increased to 12% at 12 months). CONCLUSION: From partners' perspectives, prostate cancer therapy has negative impact on sexual relationships and appears to worsen over time.

Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis.

Much has been written about the relationship between high medical expenses and the likelihood of filing for bankruptcy, but the relationship between receiving a cancer diagnosis and filing for bankruptcy is less well understood. We estimated the incidence and relative risk of bankruptcy for people age twenty-one or older diagnosed with cancer compared to people the same age without cancer by conducting a retrospective cohort analysis that used a variety of medical, personal, legal, and bankruptcy sources covering the Western District of Washington State in US Bankruptcy Court for the period 1995-2009. We found that cancer patients were 2.65 times more likely to go bankrupt than people without cancer. Younger cancer patients had 2-5 times higher rates of bankruptcy than cancer patients age sixty-five or older, which indicates that Medicare and Social Security may mitigate bankruptcy risk for the older group. The findings suggest that employers and governments may have a policy role to play in creating programs and incentives that could help people cover expenses in the first year following a cancer diagnosis.

Referral and treatment patterns among patients with stages III and IV non-small-cell lung cancer.

PURPOSE: Little is known about how referrals to different cancer specialists influence cancer care for non-small-cell lung cancer (NSCLC). Among Medicare enrollees, we identified factors of patients and their primary care physician that were associated with referrals to cancer specialists, and how the types of cancer specialists seen correlated with delivery of guideline-based therapies (GBTs). METHODS: Data from patients with stages III and IV NSCLC included in the SEER-Medicare database were linked to their physicians in the American Medical Association Masterfile database. Using logistic regression, we (1) identified patient and physician factors that were associated with referrals to cancer specialists (medical oncologists, radiation oncologists, and surgeons); (2) identified the types of referral to cancer specialists that predicted greater likelihood of receiving GBT (per National Comprehensive Cancer Network guidelines). RESULTS: A total of 28,977 patients with NSCLC diagnosed from January 1, 2000 to December 31, 2005 met eligibility criteria. Younger age, white race, higher income, and primary physician specialty other than family practice predicted higher likelihood of referrals to medical oncologists (P < .01 for all predictors). Seeing the three types of cancer specialists predicted higher likelihood of GBT (stage IIIA: odds ratio [OR] = 20.6; P < .001; IIIB: OR = 77.2; P < .001; and IV: OR = 1.2; P = .011), compared with seeing a medical oncologist only. Use of GBTs increased over the study period (42% to 48% from 2000 to 2005; P < .001). CONCLUSION: Referrals to all types of cancer specialists increased the likelihood of treatment with standard therapies, particularly in stage III patients. However, racial and income disparities still prevent optimal referrals to cancer specialists.

Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients.

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors- group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.

Adverse events associated with bevacizumab and chemotherapy in older patients with metastatic colorectal cancer.

BACKGROUND: The safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients. PATIENTS AND METHODS: Patients age ≥65 were identified from SEER-Medicare and categorized by mCRC diagnosis pre and post bevacizumab approval (2001-2003 vs. 2005-2007). Preexisting conditions known to increase bevacizumab-related AE risk were identified in the year before diagnosis. Factors associated with bevacizumab receipt were identified using logistic regression. Incidence rates for all AEs and specific serious AEs were determined. Risk factors for first AE were determined by competing risks regression. RESULTS: Of 6821 patients, 3282 (48%) were diagnosed in 2005-2007 of whom 19% received first-line bevacizumab. Likelihood of bevacizumab receipt was lower in patients age ≥ 75 (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.36-0.47), nonwhite patients (OR, 0.67; 95% CI, 0.55-0.81), patients with higher comorbidity index (OR, 0.52; 95% CI, 0.43-0.62), and patients with preexisting cerebrovascular disease (OR, 0.49; 95% CI, 0.33-0.73). AE incidence rate was not increased among first-line bevacizumab recipients relative to first-line chemotherapy recipients. In a competing risk regression adjusting for potential confounders, bevacizumab receipt (2005-2007) was not associated with an increased risk of first AE compared with chemotherapy alone (2001-2007) (hazard ratio, 0.97; 95% CI, 0.87-1.08). CONCLUSION: In an older mCRC population, bevacizumab receipt was less likely in older (age ≥ 75) nonwhite patients with preexisting cerebrovascular comorbidities. First-line bevacizumab was not associated with increased AE incidence or risk of first AE compared with chemotherapy alone.

Health insurer policies toward risk-stratified colorectal cancer screening: a survey of health plan medical directors.

OBJECTIVES: We sought to determine whether health insurance coverage of colorectal cancer (CRC) screening varied based on risk. BACKGROUND: Population-wide screening guidelines for cancer often incorporate risk information, with modified screening recommendations for those at higher risk due to family history or other factors. METHODS: In a nationwide Internet- and mail-based survey of health insurance plan medical directors, respondents were asked about their organization's policies towards coverage of CRC screening for persons at average and higher risk of CRC. Additional questions asked about whether the insurer had a definition of increased risk, and coverage of genetic testing for familial CRC syndromes. RESULTS: Survey invitations were sent to 1158 medical directors; 133 (11%) completed the survey. All plans covered screening for average and high-risk persons. The onset of screening was earlier and intervals were more frequent for higher risk compared to average risk persons, with most respondents stating coverage was determined by "physician discretion." While 75% had a definition of high risk, only 55% covered genetic testing. CONCLUSIONS: Most insurers offer enhanced coverage of CRC screening, most commonly following the discretion of the physician. Whether this coverage results in earlier, more frequent, or more complete screening of higher risk persons remains uncertain.

Complementary and alternative medicine use, patient-reported outcomes, and treatment satisfaction among men with localized prostate cancer.

OBJECTIVE: To evaluate the association between complementary and alternative medicine (CAM) use, satisfaction with treatment, and patient-reported outcomes after treatment. METHODS: The Prostate CAncer Therapy Selection Study prospectively surveyed patients newly diagnosed with localized prostate cancer about their treatment decision-making process and outcomes. The Prostate CAncer Therapy Selection Study recruited patients from 3 geographic areas through hospital-based urology clinics and community urology practices. RESULTS: More than 700 patients completed the baseline and follow-up surveys. More than 50% of respondents reported using CAM; this decreased to 39% if prayer was excluded as a type of CAM. On multivariate analysis, factors related to communication with the treating physician, but not CAM use, were associated with treatment satisfaction. The likelihood of stability or improvement in urinary, bowel, and sexual function at 6 months was related to the choice of primary therapy but was unrelated to CAM use. CONCLUSION: In the present prospective observational study, CAM use was highly prevalent but unrelated to treatment satisfaction or changes in functional status. The effect of CAM on these endpoints remains to be established in comparative effectiveness studies.

Prevalence of alcohol misuse among men and women undergoing major noncardiac surgery in the Veterans Affairs health care system.

BACKGROUND: Patients who screen positive for alcohol misuse on the Alcohol Use Disorder Identification Test Consumption Questionnaire (AUDIT-C ≥5 points) have significantly increased postoperative complications. Severe alcohol misuse (AUDIT-C ≥9 points) is associated with increased postoperative health care use; however, little is known about the prevalence of alcohol misuse in demographic and clinical subgroups of surgical patients. METHODS: The prevalence of alcohol misuse was evaluated among 10,284 patients (9,771 men and 513 women) who underwent major noncardiac surgery in Veterans Affairs (VA) hospitals during the fiscal years 2004 to 2006 and completed the AUDIT-C. Sex-stratified analyses evaluated prevalence rates of alcohol misuse (AUDIT-C ≥5) and severe misuse (AUDIT-C ≥9) across demographic and clinical subgroups. RESULTS: Overall, 1,607 (16%) men and 24 (5%) women screened positive for alcohol misuse (AUDIT-C ≥5) in the year before operation, with 4% and 2% screening positive for severe misuse (AUDIT-C ≥9), respectively. Alcohol misuse was more common among men who were <60 years of age, divorced or separated, current smokers, or American Stoke Association class 1 or 2, and those with cirrhosis/hepatitis or substance use disorders. Among patients with alcohol misuse, 36% of men and 58% of women were American Society of Anesthesiologists class 1 or 2, and most did not have diagnoses that were commonly associated with alcohol misuse. CONCLUSION: Alcohol misuse is relatively common in male surgical patients. Moreover, surgical patients undergoing operation who screen positive for alcohol misuse are often relatively healthy, without health problems that might alert providers to their alcohol misuse in the absence of screening.

A network meta-analysis of therapies for previously untreated chronic lymphocytic leukemia.

BACKGROUND: Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL. METHODS: We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option. RESULTS: Five RCTs were included in our comparison network. Overall, patients were younger (59-65 years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32). CONCLUSION: Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.

Risk factors for financial hardship in patients receiving adjuvant chemotherapy for colon cancer: a population-based exploratory analysis.

PURPOSE: Characteristics that predispose patients to financial hardship during cancer treatment are poorly understood. We therefore conducted a population-based exploratory analysis of potential factors associated with financial hardship and treatment nonadherence during and following adjuvant chemotherapy for colon cancer. PATIENTS AND METHODS: Patients diagnosed with stage III colon cancer between 2008 and 2010 were identified from a population-based cancer registry representing 13 counties in Washington state. Patients were asked to complete a comprehensive survey on treatment-related costs. Patients were considered to have experienced financial hardship if they accrued debt, sold or refinanced their home, borrowed money from friends or family, or experienced a 20% or greater decline in their annual income as a result of treatment-related expenses. Logistic regression analysis was used to investigate factors associated with financial hardship and treatment nonadherence. RESULTS: A total of 284 responses were obtained from 555 eligible patients (response rate, 51.2%). Nearly all patients in the final sample were insured during treatment. In this sample, 38% of patients reported one or more financial hardships as a result of treatment. The factors most closely associated with treatment-related financial hardship were younger age and lower annual household income. Younger age, lower income, and unemployment or disability (which occurred in most instances following diagnosis) were most closely associated with treatment nonadherence. CONCLUSION: A significant proportion of patients undergoing adjuvant chemotherapy for stage III colon cancer may experience financial hardship, despite having health insurance coverage. Interventions to help at-risk patients early on during therapy may prevent long-term financial adverse effects.

Colony-stimulating factor use and impact on febrile neutropenia among patients with newly diagnosed breast, colorectal, or non-small cell lung cancer who were receiving chemotherapy.

STUDY OBJECTIVE: To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC). DESIGN: Retrospective claims analysis. DATA SOURCES: The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records. PATIENTS: A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy. MEASUREMENTS AND MAIN RESULTS: Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia. CONCLUSION: The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes.

Is distance to provider a barrier to care for medicaid patients with breast, colorectal, or lung cancer?

PURPOSE: Distance to provider might be an important barrier to timely diagnosis and treatment for cancer patients who qualify for Medicaid coverage. Whether driving time or driving distance is a better indicator of travel burden is also of interest. METHODS: Driving distances and times from patient residence to primary care provider were calculated for 3,917 breast, colorectal (CRC) and lung cancer Medicaid patients in Washington State from 1997 to 2003 using MapQuest.com. We fitted regression models of stage at diagnosis and time-to-treatment (number of days between diagnosis and surgery) to test the hypothesis that travel burden is associated with timely diagnosis and treatment of cancer. FINDINGS: Later stage at diagnosis for breast cancer Medicaid patients is associated with travel burden (OR = 1.488 per 100 driving miles, P= .037 and OR = 1.270 per driving hour, P= .016). Time-to-treatment after diagnosis of CRC is also associated with travel burden (14.57 days per 100 driving miles, P= .002 and 5.86 days per driving hour, P= .018). CONCLUSIONS: Although travel burden is associated with timely diagnosis and treatment for some types of cancer, we did not find evidence that driving time was, in general, better at predicting timeliness of cancer diagnosis and treatment than driving distance. More intensive efforts at early detection of breast cancer and early treatment of CRC for Medicaid patients who live in remote areas may be needed.

AUDIT-C alcohol screening results and postoperative inpatient health care use.

BACKGROUND: Alcohol screening scores ≥5 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission. STUDY DESIGN: This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status, surgical category, relative value unit, and time from AUDIT-C to surgery. Patients with AUDIT-C scores indicating low-risk drinking (scores 1 to 4) were the referent group. RESULTS: Adjusted analyses revealed that among eligible surgical patients (n = 5,171), those with the highest AUDIT-C scores (ie, 9 to 12) had longer postoperative hospital length of stay (5.8 [95% CI, 5.0-6.7] vs 5.0 [95% CI, 4.7-5.3] days), more ICU days (4.5 [95% CI, 3.2-5.8] vs 2.8 [95% CI, 2.6-3.1] days), and increased probability of return to the operating room (10% [95% CI, 6-13%] vs 5% [95% CI, 4-6%]) in the 30 days after surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS: AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions.

Complementary and alternative medicine use among newly diagnosed prostate cancer patients.

PURPOSE: We surveyed prostate cancer patients about complementary and alternative medicine (CAM) use and evaluated patient factors that correlated with CAM use 6 months following diagnosis. METHODS: The Prostate CAncer Therapy Selection study was a prospective, observational multi-site study of men's treatment decision-making process after a diagnosis of local stage prostate cancer. Recruitment occurred in community urology practices in Washington State, hospital-based urology clinics affiliated with the University of Southern California, and Kaiser Permanente in Northern California. Eligible study participants included men over age 21 diagnosed with local stage prostate cancer between May 1, 2005 and December 31, 2006. RESULTS: Fifty-two percent of survey respondents (379) reported using one or more types of CAM. Of the patients, 51% used one CAM method, 26% used two methods, and 23% used three or more methods. The most commonly reported category was mind-body therapies (65%). Only 43% of patients discussed their CAM use with a health professional; of those, 20% informed their primary care physician and 30% told the doctor managing their prostate cancer care. Less than half thought the CAM they used was "very helpful", but a majority thought it was somewhat helpful for their condition. CONCLUSIONS: Further research is needed to characterize the goals prostate cancer patients have for CAM, whether the treatments met those goals, and how this translates into the perceived helpfulness of these therapies. The implications of patients not discussing CAM use with health professionals at the time of prostate cancer treatment need further studies.

Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients.

Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses administered at the traditional frequency of every 6 hours can be targeted ((T)Bu) to a patient-specific concentration at steady state (C(ss)) using therapeutic drug monitoring (TDM). In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of daily (T)Bu with pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis was conducted in 87 adults receiving daily (T)Bu as part of cyclophosphamide followed by (T)BU (CY/(T)BU), fludarabine monophosphate (fludarabine) followed by (T)BU, or (T)BU concurrent with fludarabine conditioning. The desired C(ss) was achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was not associated with sex or age, but was associated with the day of dosing and conditioning regimen (P = .0016). In patients receiving CY/(T)BU, no differences in clearance were found between dosing days (P > .36); however, clearance decreased significantly in patients receiving fludarabine-based regimens (P = .0016). Busulfan clearance and C(ss) estimates from pharmacokinetic sampling over 8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of individual patient concentration-time data over 6 hours could not reliably estimate busulfan clearance or C(ss).

Association between alcohol screening results and hospitalizations for trauma in Veterans Affairs outpatients.

BACKGROUND: Alcohol consumption is a risk factor for traumatic injury, but it is unknown whether responses to alcohol screening questionnaires administered routinely in primary care are associated with subsequent hospitalization for traumatic injury. OBJECTIVE: We evaluated the association between alcohol screening scores and the risk for subsequent hospitalizations for trauma among Veterans Affairs (VA) general medicine patients. METHOD: This study included VA outpatients (n = 32,623) at seven sites who returned mailed surveys (1997-1999). Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores grouped patients into six drinking categories representing nondrinkers, screen-negative drinkers, and drinkers who screened positive for mild, moderate, severe, and very severe alcohol misuse (scores 0, 1-3, 4-5, 6-7, 8-9, 10-12, respectively). VA administrative and Medicare data identified primary discharge diagnoses for trauma. Cox proportional hazard models were used to estimate the risk of trauma-related hospitalization for each drinking group adjusted for demographics, smoking, and comorbidity. RESULTS: Compared with screen-negative drinkers, patients with severe and very severe alcohol misuse (AUDIT-C 8-9 and ≥10) were at significantly increased risk for trauma-related hospitalization over the follow-up period (adjusted hazard ratios AUDIT-C: 8-9 2.06, 95% confidence interval (CI) 1.31- 3.24 and AUDIT-C≥10 2.13, 95% CI 1.32-3.42). CONCLUSIONS: Patients with severe and very severe alcohol misuse had a twofold increased risk of hospital admission for trauma compared to drinkers without alcohol misuse. SCIENTIFIC SIGNIFICANCE: Alcohol screening scores could be used to provide feedback to patients regarding risk of trauma-related hospitalization. Findings could be used by providers during brief alcohol-related interventions with patients with alcohol misuse.

An inducible cytochrome P450 3A4-dependent vitamin D catabolic pathway.

Vitamin D(3) is critical for the regulation of calcium and phosphate homeostasis. In some individuals, mineral homeostasis can be disrupted by long-term therapy with certain antiepileptic drugs and the antimicrobial agent rifampin, resulting in drug-induced osteomalacia, which is attributed to vitamin D deficiency. We now report a novel CYP3A4-dependent pathway, the 4-hydroxylation of 25-hydroxyvitamin D(3) (25OHD(3)), the induction of which may contribute to drug-induced vitamin D deficiency. The metabolism of 25OHD(3) was fully characterized in vitro. CYP3A4 was the predominant source of 25OHD(3) hydroxylation by human liver microsomes, with the formation of 4ß,25-dihydroxyvitamin D(3) [4ß,25(OH)(2)D(3)] dominating (V(max)/K(m) = 0.85 ml · min(-1) · nmol enzyme(-1)). 4ß,25(OH)(2)D(3) was found in human plasma at concentrations comparable to that of 1α,25-dihydroxyvitamin D(3), and its formation rate in a panel of human liver microsomes was strongly correlated with CYP3A4 content and midazolam hydroxylation activity. Formation of 4ß,25(OH)(2)D(3) in primary human hepatocytes was induced by rifampin and inhibited by CYP3A4-specific inhibitors. Short-term treatment of healthy volunteers (n = 6) with rifampin selectively induced CYP3A4-dependent 4ß,25(OH)(2)D(3), but not CYP24A1-dependent 24R,25-dihydroxyvitamin D(3) formation, and altered systemic mineral homeostasis. Our results suggest that CYP3A4-dependent 25OHD(3) metabolism may play an important role in the regulation of vitamin D(3) in vivo and in the etiology of drug-induced osteomalacia.

Health care use and primary prophylaxis with colony-stimulating factors.

OBJECTIVES: We examined health care use in conjunction with primary prophylaxis use of colony stimulating factors (CSF) during patients' initial course of chemotherapy. METHODS: This retrospective cohort study identified adults aged 25 years and older with a diagnosis of breast, colorectal, or nonsmall cell lung cancer between 2002 and 2005 from the Western Washington Surveillance Epidemiology and End Results Puget Sound registry. We linked these records to health insurance claims from four payers representing 75% of those insured in the state. Claims records were used to determine chemotherapy regimen type, CSF use, febrile neutropenia occurrences, and supportive care. Chemotherapy regimens were categorized as conferring high, intermediate, or low risk of myelosuppression according to the National Comprehensive Cancer Network guidelines. CSF use was described as primary prophylaxis, other, or none. Antibiotics and antifungal and antiviral agents per National Comprehensive Cancer Network guidelines for supportive care for cancer infection were categorized using Healthcare Common Procedure Coding System and National Drug Code assignments. RESULTS: Use of CSF as primary prophylaxis is not significantly associated with a reduction in antibiotic use or inpatient or outpatient visits. Primary prophylactic CSF use was associated with less use of antiviral drugs. CONCLUSIONS: CSF use is not associated with a reduction in health care use, with the exception of antiviral drug use. Given the expense associated with CSF use, pragmatic trials and additional research are needed to further assess the affects of CSF on health care use.