A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only.

BACKGROUND: Patients with liver-only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first-line treatment for KRAS wild-type mCRC with liver-only metastasis. METHODS: Patients received FOLFOXIRI (5-FU, 3,200 mg/m(2), 48-hour continuous intravenous (i.v.) infusion; leucovorin, 200 mg/m(2) i.v.; irinotecan, 125 mg/m(2); oxaliplatin, 85 mg/m(2) i.v.) and panitumumab (6 mg/kg i.v.) on day 1 of 14-day cycles. Patients were restaged and evaluated for surgery every four cycles. Planned enrollment was originally 49 patients. The primary endpoint was objective response rate. RESULTS: Fifteen patients (median age: 55 years; 87% male) received a median 6 cycles of treatment (range: 1-33 cycles); 10 patients (67%) were surgical candidates at baseline. Twelve patients were evaluable for clinical response; 9 (60%) achieved partial response. Ten patients underwent surgery; all were complete resections and pathologic partial response. Treatment-related grade 3 adverse events included diarrhea (33%) and rash (20%). Enrollment was halted because of emerging data on expanded KRAS/NRAS mutations beyond the region we initially examined, and the potential for negative interaction with oxaliplatin-based therapy. Eight patients underwent expanded KRAS/NRAS analysis outside exon 2; no additional mutations were found. CONCLUSION: KRAS/NRAS mutations outside the region tested in this study were recently shown to be associated with inferior survival on similar treatment regimens. Therefore, this trial was stopped early. This regimen remains a viable option for patients with liver-only mCRC in the KRAS/NRAS wild-type population. Enrollment criteria on future studies should include testing for the newly identified mutations.

Managed care, hospice use, site of death, and medical expenditures in the last year of life.

BACKGROUND: We examined deaths of Medicare beneficiaries in Massachusetts and California to evaluate the effect of managed care on the use of hospice and site of death and to determine how hospice affects the expenditures for the last year of life. METHODS: Medicare data for beneficiaries in Massachusetts (n = 37 933) and California (n = 27 685) who died in 1996 were merged with each state's death certificate files to determine site and cause of death. Expenditure data were Health Care Financing Administration payments and were divided into 30-day periods from the date of death back 12 months. RESULTS: In Massachusetts, only 7% of decedents were enrolled in managed care organizations (MCOs); in California, 28%. More than 60% of hospice users had cancer. Hospice use was much lower in Massachusetts than in California (12% vs 18%). In both states, decedents enrolled in MCOs used hospice care much more than those enrolled in fee-for-service plans (17% vs 11% in Massachusetts and 25% vs 15% in California). This pattern persisted for those with cancer and younger (aged 65-74 years) decedents. Decedents receiving hospice care were significantly (P<.001 for both) less likely to die in the hospital (11% vs 43% in Massachusetts and 5% vs 43% in California). Enrollment in MCOs did not affect the proportion of in-hospital deaths (those enrolled in fee-for-service plans vs MCOs: 40% vs 39% in Massachusetts; and 37% vs 34% in California). Expenditures in the last year of life were $28 588 in Massachusetts and $27 814 in California; about one third of the expenditures occurred in the last month before death. Hospital services accounted for more than 50% of all expenditures in both states, despite 77% of decedents being hospitalized in Massachusetts and just 55% being hospitalized in California. Among patients with cancer, expenditures were 13% to 20% lower for those in hospice. CONCLUSIONS: Medicare-insured decedents in California were more than 4 times more likely to be enrolled in MCOs, were 50% more likely to use a hospice, and had a 30% lower hospitalization rate than decedents in Massachusetts, yet there are few differences in out-of-hospital deaths or expenditures in the last year of life. However, patients with cancer using hospice did have significant savings.

Addressing alcohol problems in primary care: a cluster randomized, controlled trial of a systems intervention. The screening and intervention in primary care (SIP) study.

BACKGROUND: Screening and intervention for alcohol problems can reduce drinking and its consequences but are often not implemented. OBJECTIVE: To test whether providing physicians with patients' alcohol screening results and simple individualized recommendations would affect the likelihood of a physician's having a discussion with patients about alcohol during a primary care visit and would affect subsequent alcohol use. DESIGN: Cluster randomized, controlled trial. SETTING: Urban academic primary care practice. PARTICIPANTS: 41 faculty and resident primary care physicians and 312 patients with hazardous drinking. INTERVENTIONS: Providing physicians with alcohol screening results (CAGE questionnaire responses, alcohol consumption, and readiness to change) and recommendations for their patients at a visit. MEASUREMENTS: Patient self-report of discussions about alcohol use immediately after the physician visit and alcohol use 6 months later. RESULTS: Of 312 patients, 240 visited faculty physicians, 301 (97%) completed the outcome assessment after the office visit, and 236 (76%) were followed for 6 months. Faculty physicians in the intervention group tended to be more likely than faculty physicians in the control group to give patients advice about drinking (adjusted proportion, 64% [95% CI, 47% to 79%] vs. 42% [CI, 33% to 53%]) and to discuss problems associated with alcohol use (74% [CI, 59% to 85%] vs. 51% [CI, 39% to 62%]). Resident physicians' advice and discussions did not differ between groups. Six months later, patients who saw resident physicians in the intervention group had fewer drinks per drinking day (adjusted mean number of drinks, 3.8 [CI, 1.9 to 5.7] versus 11.6 [CI, 5.4 to 17.7]). CONCLUSIONS: Although effects seem to differ by physician level of training, prompting physicians with alcohol screening results and recommendations for action can modestly increase discussions about alcohol use and advice to patients and may decrease alcohol consumption.

Early antidepressant therapy for elderly patients.

PURPOSE: We studied factors affecting the management of depression in older patients, especially the use of early antidepressant therapy. METHODS: We recruited 128 primary care physicians to view one version of a 5-minute videotape of an elderly patient with somatic symptoms that were suggestive of depression, and to complete an interview that assessed decision making. Using an experimental factorial design, 16 versions of the videotape were produced, holding constant the clinical features of the case, while varying the patient's age, race, sex, and socioeconomic status. Dependent variables were the physicians' probability assessment of depression and the recommendation of antidepressant medication after the first visit. RESULTS: Depression was considered a possible diagnosis by 121 physicians (95%) and the most likely diagnosis by 69 (54%). Sixteen physicians (13%) recommended antidepressant therapy after the first visit, and they were less likely than other physicians to order initial laboratory tests to assess the possibility of other conditions. Recommendations for antidepressant therapy was not associated with patient age, sex, race, or socioeconomic status, or with physician sex, race, or experience. Family physicians were more likely than internists to recommend an antidepressant (19% [12/64] vs. 6% [4/64], P = 0.04). CONCLUSION: Based on a 5-minute vignette, physicians were likely to recognize depression, independent of patient characteristics. Those recommending early antidepressant therapy were more likely to be in family medicine and less likely to investigate other diagnoses initially.

Profiling nursing homes using Bayesian hierarchical modeling.

OBJECTIVES: New methods developed to improve the statistical basis of provider profiling may be particularly applicable to nursing homes. We examine the use of Bayesian hierarchical modeling in profiling nursing homes on their rate of pressure ulcer development. DESIGN: Observational study using Minimum Data Set data from 1997 and 1998. SETTING: A for-profit nursing home chain. PARTICIPANTS: Residents of 108 nursing homes who were without a pressure ulcer on an index assessment. MEASUREMENTS: Nursing homes were compared on their performance on risk-adjusted rates of pressure ulcer development calculated using standard statistical techniques and Bayesian hierarchical modeling. RESULTS: Bayesian estimates of nursing home performance differed considerably from rates calculated using standard statistical techniques. The range of risk-adjusted rates among nursing homes was 0% to 14.3% using standard methods and 1.0% to 4.8% using Bayesian analysis. Fifteen nursing homes were designated as outliers based on their z scores, and two were outliers using Bayesian modeling. Only one nursing home had greater than a 50% probability of having a true rate of ulcer development exceeding 4%. CONCLUSIONS: Bayesian hierarchical modeling can be successfully applied to the problem of profiling nursing homes. Results obtained from Bayesian modeling are different from those obtained using standard statistical techniques. The continued evaluation and application of this new methodology in nursing homes may ensure that consumers and providers have the most accurate information regarding performance.

Quality improvement implementation in the nursing home.

OBJECTIVE: To examine quality improvement (QI) implementation in nursing homes, its association with organizational culture, and its effects on pressure ulcer care. DATA SOURCES/STUDY SETTING: Primary data were collected from staff at 35 nursing homes maintained by the Department of Veterans Affairs (VA) on measures related to QI implementation and organizational culture. These data were combined with information obtained from abstractions of medical records and analyses of an existing database. STUDY DESIGN: A cross-sectional analysis of the association among the different measures was performed. DATA COLLECTION/EXTRACTION METHODS: Completed surveys containing information on QI implementation, organizational culture, employee satisfaction, and perceived adoption of guidelines were obtained from 1,065 nursing home staff. Adherence to best practices related to pressure ulcer prevention was abstracted from medical records. Risk-adjusted rates of pressure ulcer development were calculated from an administrative database. PRINCIPAL FINDINGS: Nursing homes differed significantly (p<.001) in their extent of QI implementation with scores on this 1 to 5 scale ranging from 2.98 to 4.08. Quality improvement implementation was greater in those nursing homes with an organizational culture that emphasizes innovation and teamwork. Employees of nursing homes with a greater degree of QI implementation were more satisfied with their jobs (a 1-point increase in QI score was associated with a 0.83 increase on the 5-point satisfaction scale, p<.001) and were more likely to report adoption of pressure ulcer clinical guidelines (a 1-point increase in QI score was associated with a 28 percent increase in number of staff reporting adoption, p<.001). No significant association was found, though, between QI implementation and either adherence to guideline recommendations as abstracted from records or the rate of pressure ulcer development. CONCLUSIONS: Quality improvement implementation is most likely to be successful in those VA nursing homes with an underlying culture that promotes innovation. While QI implementation may result in staff who are more satisfied with their jobs and who believe they are providing better care, associations with improved care are uncertain.

The unexpected influence of physician attributes on clinical decisions: results of an experiment.

UNLABELLED: This experiment was designed to determine: (1) whether patient attributes (specifically a patient's age, gender, race, and socioeconomic status) independently influence clinical decision-making; and (2) whether physician characteristics alone (such as their gender, age, race, and medical specialty), or in combination with patient attributes, influence medical decision-making. METHODS: An experiment was conducted in which 16 (= 2(4)) videotapes portraying patient-physician encounters for two medical conditions (polymyalgia rheumatica (PMR) and depression) were randomly assigned to physicians for viewing. Each video presented a combination of four patient attributes (65 years or 80 years of age; male or female; black or white; blue or white collar occupation). Steps were taken to enhance external validity. One hundred twenty-eight eligible physicians were sampled from the northeastern United States, with numbers balanced across 16 (= 2(4)) strata generated from the following characteristics (male or female; < 15 or > or = 15 years since graduation; black or white; internists or family practitioners). The outcomes studied were: 1) the most likely diagnosis; 2) level of certainty adhering to that diagnosis; and 3) the number of tests that would be ordered. RESULTS: Patient attributes (namely age, race, gender, and socioeconomic status) had no influence on the three outcomes studied (the most likely diagnosis, the level of certainty, and test ordering behavior). This was consistent across the two medical conditions portrayed (PMR and depression). In contrast, characteristics of physicians (namely their medical specialty, race, and age) interactively influenced medical decision-making. CONCLUSION: Epidemiologically important patient attributes (which Bayesian decision theorists hold should be influential) had no effect on medical decision-making for the two conditions, while clinically extraneous physician characteristics (which should not be influential) had a statistically significant effect. The validity of idealized theoretical approaches to medical decision making and the usefulness of further observational approaches are discussed.

Depression management in medical clinics: does healthcare sector make a difference?

Medical providers often fail to treat depression. We examined whether treatment is more aggressive in a setting with accessible mental health resources, the Veterans Health Administration (VA). VA and non-VA primary care physicians and medical specialists viewed a videotape vignette portraying a patient meeting criteria for major depression and then answered interviewer-administered questions about management. We found that 24% of VA versus 15% of non-VA physicians would initiate guideline-recommended treatment (antidepressants or mental health referral, or both) (P = .09). Among those who identified depression as likely, 42% of VA versus 19% of non-VA physicians would treat (P = .002): 23% versus 3% recommended mental health referral (P < .001) and 21% versus 17% an antidepressant (P = .67). Although many patients with major depression may not receive guideline-recommended management, VA physicians do initiate mental health referral more often than do non-VA physicians. Access to mental health services may prove valuable in the campaign to increase physician adherence to depression clinical guidelines.

Technique and outcomes of abdominal incisional hernia repair using a synthetic composite mesh: a report of 455 cases.

BACKGROUND: Abdominal wall hernias are a frequent and formidable challenge for general surgeons. Several different surgical techniques and types of mesh prosthetics are available for repair. We evaluated outcomes of an open ventral hernia repair using a synthetic composite mesh. STUDY DESIGN: We prospectively collected data on consecutive patients undergoing open ventral hernia repair using a synthetic composite mesh from January 1, 2000 to December 31, 2005 at four large medical centers. Four surgeons used a standardized surgical procedure for all patients. RESULTS: The study consisted of 455 patients with an average age of 56 years; 54% were men. Sixty-nine percent of the patients underwent repairs for recurrent hernias. Mean defect size was 44 cm(2), and mean mesh size was 213 cm(2). Average length of hospital stay was 1.1 days. Thirty-one patients had 33 early complications (7%), and 3 patients (0.7%) required reoperation (one each for seroma, bowel injury, and wound breakdown). Early infection occurred in four patients (0.9%), and one patient required reoperation and graft removal. Late complications occurred in nine patients (2%), with two patients requiring reoperation. Late infections occurred in two patients (0.4%); both required antibiotic treatment. Recurrent hernias were observed in 6 patients (1%; 6 of 450 because of 5 patients with unknown recurrence) at a mean followup of 29.3 months. CONCLUSIONS: In this large multicenter series, open ventral hernia repair using a composite mesh resulted in a short hospital stay, moderate complication rate, low infection rate, and low recurrence rate.

Professional satisfaction experienced when caring for substance-abusing patients: faculty and resident physician perspectives.

This survey aimed to describe and compare resident and faculty physician satisfaction, attitudes, and practices regarding patients with addictions. Of 144 primary care physicians, 40% used formal screening tools; 24% asked patients' family history. Physicians were less likely (P <.05) to experience at least a moderate amount of professional satisfaction caring for patients with alcohol (32% of residents, 49% of faculty) or drug (residents 30%, faculty 31%) problems than when managing hypertension (residents 76%, faculty 79%). Interpersonal experience with addictions was common (85% of faculty, 72% of residents) but not associated with attitudes, practices, or satisfaction. Positive attitudes toward addiction treatment (adjusted odds ratio [AOR], 4.60; 95% confidence interval [95% CI], 1.59 to 13.29), confidence in assessment and intervention (AOR, 2.49; 95% CI, 1.09 to 5.69), and perceived responsibility for addressing substance problems (AOR, 5.59; CI, 2.07 to 15.12) were associated with greater satisfaction. Professional satisfaction caring for patients with substance problems is lower than that for other illnesses. Addressing physician satisfaction may improve care for patients with addictions.