Prestroke physical activity and early functional status after stroke.

BACKGROUND: The importance of physical activity as a modifiable risk factor for stroke in particular and cardiovascular disease in general is well documented. The effect of exercise on stroke severity and stroke outcomes is less clear. This study aimed to assess that effect. METHODS: Data collected for patients enrolled in the Ischemic Stroke Genetics Study were reviewed for prestroke self-reported levels of activity and four measures of stroke outcome assessed at enrollment and approximately 3 months after enrollment. Logistic regression was used to assess the association between physical activity and stroke outcomes, unadjusted and adjusted for patient characteristics. RESULTS: A total of 673 patients were enrolled; 50.5% reported aerobic physical activity less than once a week, 28.5% reported aerobic physical activity one to three times weekly, and 21% reported aerobic physical activity four times a week or more. Patients with moderate and high levels of physical activity were more likely to have higher Barthel Index (BI) scores at enrollment. A similar association was detected for exercise and good outcomes for the Oxford Handicap Scale (OHS). After 3 months of follow-up, moderate activity was still associated with a high BI score. No significant association was detected for activity and the OHS or Glasgow Outcome Scale at follow-up after adjustment for patient characteristics. CONCLUSIONS: Higher levels of self-reported prestroke physical activity may be associated with functional advantages after stroke. Our findings should be seen as exploratory, requiring confirmation, ideally in a longitudinal study of exercise in an older population.

Effectiveness of health education to increase screening for cervical cancer among eastern-band Cherokee Indian women in North Carolina.

BACKGROUND: The North Carolina Native American Cervical Cancer Prevention Project was a 5-year, National Cancer Institute-funded trial of health education designed to increase screening for cervical cancer among Native-American women in North Carolina. PURPOSE: This study was conducted to evaluate the effectiveness of this education program in the Eastern-Band Cherokee target population. METHODS: Cherokee tribal lands were mapped and all households (N = 2223) were listed to ensure maximum coverage of the eligible population (women, aged 18 years and older, who were enrolled tribal members). Eligible women were identified by the use of a brief questionnaire administered to an adult member of the household. Of the 1279 households with eligible women, 1020 (79.8%) agreed to participate. The intervention was an individualized health education program delivered by female Cherokee lay health educators. The participants were randomly assigned to receive or not to receive the intervention (i.e., to program and control groups, respectively) by use of the Solomon Four-Group design. Data were collected in face-to-face interviews conducted in the participant's home. Of the 996 women who were ultimately enrolled, 540 were randomly assigned to receive a pretest (preintervention) interview that involved administration of a 96-item questionnaire designed to collect data on knowledge, intentions, and behaviors related to cervical cancer; of these 540 women, 263 were randomly assigned to receive the education program. The remaining 456 women did not receive the pretest, but 218 were randomly assigned to receive the education program. Six months after receiving the education program, the women in all four groups were administered a post-test that was identical to the pretest. Logistic regression was used to assess the effects of the pretest and the educational program. All P values resulted from two-sided statistical tests. RESULTS: Eight hundred and fifteen (81.8%) of the 996 participants completed the post-test interview. The remaining 181 women who were lost to follow-up were evenly distributed among the four study groups. At the post-test, 282 (73.2%) of the 385 women who received the education program reported having had a Pap smear following the intervention, compared with 275 (64%) of the 430 control subjects. Women who received the education program were more likely to answer all knowledge items correctly on the post-test (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.08-4.39) and to report having obtained a Pap smear in the past year (OR = 2.06, 95% CI = 1.14-3.72) than women in the control groups. CONCLUSION: Women who received the education program exhibited a greater knowledge about cervical cancer prevention and were more likely to have reported having had a Pap smear within the past year than women who did not receive the program.

Cathepsin D as a prognostic indicator for node-negative breast cancer patients using both immunoassays and enzymatic assays.

This is a retrospective study on 162 node-negative patients, with both biochemical and clinical factors being measured for determination of prognostic markers. Steroid receptors were measured on all tumors, while tumor size, histological grade, ploidy status, and cell cycle kinetics indicators could not be found or measured on 25 or less of the patient group. The primary focus of this study was the measurement of cathepsin D, analyzed by two different procedures, and 161 of the 162 patients had at least one value. The antigenic assay was performed using the US-CIS kit, and it was sensitive and reproducible. A biochemical assay using the enzymatic activity of cathepsin D was developed, and it gave proportional values, compared to the antigenic assay values (r2 = 0.79). Our results indicated that the mean antigenic levels were 20% higher than the biochemical assay levels (P = 0.001). High levels of cathepsin D by the antigenic assay predicted poor relapse-free (P = 0.0001) and overall (P = 0.0004) survival. High levels of cathepsin D by the biochemical assay also predicted poor relapse-free (P = 0.031) and overall (P = 0.0013) survival. The cathepsin D values were still useful as predictors of outcome after multivariate analysis. Several other factors, such as grade and S phase, were useful as additional prognostic indicators. In conclusion, cathepsin D is the most useful marker in node-negative patients, and the analysis can be performed by both a biochemical and an antigenic assay.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PURPOSE: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. METHODS: Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. RESULTS: Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. CONCLUSION: Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. IMPLICATIONS FOR CANCER SURVIVORS: Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Combination chemotherapy (5-fluorouracil, methyl-CCNU, mitomycin C) versus 5-fluorouracil alone for advanced previously untreated colorectal carcinoma. A phase III study of the Piedmont Oncology Association.

One-hundred thirty eligible patients with advanced colorectal carcinoma who had received no prior chemotherapy were randomized to either methyl-CCNU, 70 mg/m2 orally every 6 weeks on day 1, mitomycin C, 10 mg/m2 intravenously every 6 weeks on day 1, and 5-fluorouracil (5-FU), 400 mg/m2 intravenously weekly--(MMF)--or 5-FU, 600 mg/m2 intravenously weekly (5-FU). One hundred twenty-six patients are evaluable for response. Of 62 patients treated with MMF, one (2%) achieved complete remission, and three (5%) attained partial remission. Of 64 patients treated with 5-FU, two (3%) achieved complete remission, and eight (13%) attained partial remission. The median survival for patients receiving MMF was 9.5 months compared with 10.3 months for patients receiving 5-FU. The survival distributions for the two regimens were not significantly different, either unadjusted or adjusted for pretreatment characteristics. Performance status and lactic dehydrogenase (LDH) were both significantly associated with survival. Patients with liver metastases only and normal liver function tests had a median survival of 19.8 months and a 40% response rate. This randomized phase III trial did not show any therapeutic advantage for MMF compared to 5-FU therapy alone in advanced colorectal cancer. In addition, hematologic toxicity was significantly greater with the combination (MMF) regimen.

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.

PURPOSE: To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS: Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS: One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION: In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.

Improvement of long-term survival in extensive small-cell lung cancer.

The effect of adding the epipodophyllotoxin etoposide (VP-16-213) to a standard chemotherapy regimen for patients with extensive stage small-cell lung cancer was evaluated during a randomized trial. Chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide (VAC) alone or with etoposide (EVAC). Of 139 patients enrolled, 136 patients were eligible for study and all but five were evaluable for response. The overall objective response was 46% in the VAC group v 70% in the etoposide-treated group (P = .008) with complete response (CR) rates of 12% v 29%, respectively (P = .030). Although the time to the observation of disease progression was significantly longer in the group of patients receiving etoposide (9.6 v 6.5 months, P = .010), overall survival was similar; this was probably due to administration of other agents including etoposide at the time of VAC failure. However, there were noteworthy differences in long-term (greater than or equal to 2 year) survival. Whereas only four (6%) patients treated with VAC lived 2 years, 11 (16%) of the etoposide-treated group did so (P = .100). Two-year failure-free survival was attained in one (2%) of the VAC patients and eight (11%) of the patients treated with etoposide (P = .034). Long-term survivorship, heretofore usually reported in patients with limited stage disease after a variety of treatments, may be possible with this drug combination in the setting of extensive disease.

VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.

Single agent vincristine by infusion in refractory multiple myeloma.

A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.

GM-CSF and asparaginase potentiate ara-C cytotoxicity in HL-60 cells.

In preparation for a clinical trial using GM-CSF on days 4-10 of sequential high-dose cytarabine (ara-C) and asparaginase (ASNase) on days 1-3 and 8-10, potential interactions between the protein synthesis inhibitor ASNase and GM-CSF were evaluated. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate acute myeloid leukemia (AML) cells to proliferate in vitro and in vivo. Log phase HL-60 cells were exposed to ara-C (10 microM x 3 h) and/or ASNase (10 U/ml during the last 2 h of ara-C). Ara-C and/or ASNase was removed and cells were incubated with or without GM-CSF (10 ng/ml). After 24, 48 and 72 h of GM-CSF there was no significant difference in the S phase fraction of cells exposed to ASNase prior to GM-CSF. Soft agar cloning efficiency was determined after retreatment with ara-C +/- ASNase 24 h into the GM-CSF incubation. GM-CSF enhanced cytotoxicity for all combinations, although this effect was of borderline significance (P = 0.0621); addition of ASNase to the treatment regimen significantly (P = 0.0229) enhanced cytotoxicity without any evidence of a negative interaction with GM-CSF. In addition, ara-C metabolism was assessed during simultaneous exposure to ara-C (10 microM x 3 h) +/- ASNase (10 U/ml the last 2 h) +/- GM-CSF (10 ng/ml beginning 24 h prior to ara-C). Ara-C incorporated into DNA (P = 0.0302) and ara-CTP formation (P = 0.0084 and P = 0.0003 at 2 and 3 h timepoints, respectively) were both increased significantly by GM-CSF, with modest non-significant increases with ASNase exposures. Neither ASNase nor GM-CSF inhibited the effects of the other in this in vitro model. Therefore, when appropriately scheduled, both GM-CSF and ASNase may potentiate ara-C cytotoxicity.

Tumor uptake and elimination of 2',2'-difluoro-2'-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response.

PURPOSE: We hypothesized that tumor uptake and elimination of 2',2'-difluoro-2'-deoxycytidine/2',2'-difluoro-2'-deoxycytidine 5'-triphosphate (dFdCyd/dFdCTP) would be altered after dCK gene transfer and that this change would result in an enhanced cytotoxic effect. To test this hypothesis, we examined dFdCyd/dFdCTP uptake and clearance in HT-29 human colon carcinoma xenografts in nude mice by high-performance liquid chromatography (HPLC) and fluorine-19 magnetic resonance spectroscopy (F-19 MRS). EXPERIMENTAL DESIGN: HT-29 tumors were grown from cells infected with either the retroviral vector alone (LNPO-LacZ) or vector containing the dCK gene (LNPO-dCK). HPLC and F-19 MRS analyses were performed after a single 160 mg/kg i.p. injection of dFdCyd. Tumor response was determined in animals receiving a similar dosing schedule of dFdCyd. RESULTS: HPLC experiments revealed an increased tumor accumulation of dFdCTP in xenografts overexpressing dCK compared with wild-type controls (P < or = 0.05). dFdCTP in the dCK-infected tumors was easily identified at 24 h postinjection. Conversely, no dFdCTP could be detected in the control xenografts 14 h postinjection. Subsequent F-19 MRS experiments confirmed an altered uptake, revealing a 2.5-fold greater accumulation of dFdCyd/dFdCTP in the dCK xenografts. Whereas a modest tumor growth delay was observed in the wild-type tumors receiving dFdCyd, dCK xenografts demonstrated a marked tumor growth delay following treatment (P < or = 0.05). CONCLUSIONS: These data support the hypothesis that increased expression of dCK cDNA in HT-29 xenografts results in an enhanced dFdCTP accumulation and prolonged elimination kinetics, and ultimately a potentiated in vivo tumor response to dFdCyd. Related to these effects, changes in the overall tumor metabolism of dFdCyd/dFdCTP was detectable by noninvasive F-19 MRS. These data are relevant to future preclinical and clinical studies evaluating dCK gene transfer and dFdCyd therapy.

Mortality in intensive care patients with respiratory disease. Is age important?

BACKGROUND: Age has been proposed as a criterion for health care rationing. However, the relationship of age and other prognostic factors to in-hospital mortality in older patients is unclear. The purpose of this study was to examine the effect of age on hospital mortality for patients admitted to the intensive care unit. METHODS: This historical prospective study examined 3050 admissions of patients aged 50 years and older with disease of the lower respiratory tract to intensive care units in 78 hospitals in the United States during an 18-month period (July 1987 through December 1988). The association of age with hospital mortality was examined by means of a multiple logistic regression model that included age, gender, primary discharge diagnosis, severity, and comorbid diseases. RESULTS: Variables significantly predictive of in-hospital mortality included age, severity of illness, diagnosis, and a history of chronic obstructive pulmonary disease. In contrast, gender, diabetes mellitus, congestive heart failure, angina, and stroke/transient ischemic attack were not significant predictors of mortality. Predicted mortalities varied from 0.7% to 40.7% in 50-year-old patients and from 5.5% to 78.6% in 90-year-old patients. CONCLUSIONS: Chronological age is independently associated with in-hospital mortality in patients with disease of the lower respiratory tract admitted to an intensive care unit. However, the clinical importance of this relationship is modulated by other variables, such as the primary diagnosis, the presence of comorbid conditions (chronic obstructive pulmonary disease), and the severity of the acute illness, such that use of age alone is not sufficient to predict hospital outcome.

Validation of self-reported breast and cervical cancer screening tests among low-income minority women.

The objective of the Forsyth County Cancer Screening Project is to assess barriers to breast and cervical cancer screening among low-income women and to develop an educational program to address these barriers. To properly assess the barriers, it was first necessary to determine if self-reported rates of breast and cervical cancer screening were accurate. All women who participated in the baseline survey (n = 555) were asked to provide information regarding if, where, and when they had obtained mammograms and Pap smears. Identified health care facilities were then contacted to verify this information. Approximately 80% of responses were verified for at least one of the exams with the information provided. For mammography, 77% of self-reports were correct, whereas 67% of self-reports of Pap smear screening were correct (kappa = 0.54 and 0.15, respectively). For both tests, women thought they had received them more recently than they actually had, by an average of 3 months for mammography and 23 months for Pap smears. Using validated reports of screening did not substantially change identified predictors of screening for mammography. For Pap smear screening, however, most of the identified predictors of screening became nonsignificant when medical chart reports were used instead of self-reports, suggesting that caution should be used in relying on self-reports to design programs to improve cervical cancer screening practices.

Small-cell lung cancer: a 10-year perspective.

Over the past 10 years, four clinical trials have been conducted with a total of 528 patients with previously untreated small-cell lung cancer. Trials I to III were randomized phase III studies testing the value of prophylactic cranial irradiation, immunotherapy, and etoposide, respectively. They were done in the setting of combined modality treatment with the same local chest radiotherapy (3,000 rad in 10 fractions) and combined agent chemotherapy using a nucleus of CAV (cyclophosphamide, doxorubicin, vincristine). Trial IV was a pilot study evaluating sequential hemibody radiotherapy in a combined modality treatment program with CAV. Overall, the best treatment results to date have been observed following the combination of etoposide with CAV in trial III, particularly for patients with extensive disease. This combination with or without other agents also appears to be a common component of many trials that have reported particularly good survival results in this disease.

Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases.

PURPOSE: To determine the etiology and to evaluate the clinical consequences of an extremely elevated platelet count. PATIENTS AND METHODS: A review of the medical records was performed on all patients encountered during a 5 1/2-year period who had at least one platelet count of 1,000 x 10(9)/L or greater. RESULTS: Of the total of 280 patients with extreme thrombocytosis (EXT), 231 (82%) had reactive thrombocytosis (RT), 38 (14%) had a myeloproliferative disorder (MPD), and 11 (4%) had cases of uncertain etiology. RT was more common than MPD in all age groups except those in the eighth decade and older. Symptoms of bleeding and/or vaso-occlusive phenomena were noted in association with EXT in 21 (56%) of the MPD patients but in only 10 (4%) of the RT patients. Treatment to lower the platelet count and/or inhibit platelet function was employed in 36 MPD patients and 23 RT patients. Eight patients with MPD and 34 with RT are known to have died, but no patient in either group is known to have died of a thrombotic or bleeding event when the platelet count was greater than or equal to 1,000 x 10(9)/L. CONCLUSIONS: Platelet counts greater than or equal to 1,000 x 10(9)/L should not be considered rare events in the general, acute-care hospital population, and usually represent a reactive phenomenon.

Increasing influenza immunization among high-risk patients: education or financial incentive?

PURPOSE: To determine whether an educational brochure or a lottery-type incentive increases influenza immunization rates. PATIENTS AND METHODS: In a prospective, single-blind factorial design randomized trial at an urban community health center, all high-risk patients (n = 797) seen in the preceding 18 months were randomly assigned to one of four groups: a control group; a group mailed a large print, illustrated educational brochure emphasizing factors important to patients in making a decision about influenza immunization; a group mailed a lottery-type incentive announcing that all patients receiving influenza immunization would be eligible for grocery gift certificates; and a group mailed both educational brochure and incentive. Immunization was free, available without an appointment, and recorded by a computerized tracking system. RESULTS: The group mailed the brochure was more likely to be immunized than control (odds ratio [OR] = 2.29, 95% confidence interval [CI] 1.45 to 3.61), as was the group mailed the incentive (OR = 1.68, 95% CI 1.05 to 2.68), but there was no difference between the group mailed both interventions and the control group. The effectiveness of the brochure was more striking for individuals who had not accepted immunization in the prior year (OR = 4.21, 95% CI 2.48 to 7.14), suggesting a true educational effect rather than simply a reminder. CONCLUSION: In this community health center setting, an illustrated educational brochure increased influenza immunization among high-risk patients, a lottery-type incentive was much less effective, and both together was not effective.

A preliminary analysis of health-related quality of life in the first year after permanent source interstitial brachytherapy (PIB) for clinically localized prostate cancer.

PURPOSE: To prospectively assess the health-related quality of life (HRQOL) and changes in HRQOL during the first year after permanent source interstitial brachytherapy (PIB). METHODS AND MATERIALS: Thirty-one men treated with PIB between September 1997 and March 1998 completed a quality of life (functional assessment of cancer therapy-prostate: FACT-P) and a urinary symptom questionnaire (international prostate symptom score: IPSS) prior to treatment (T0), 1 month (T1), 3 months (T3), 6 months (T6), and 12 months (T12) following PIB. All participants were treated with 125I alone. Repeated measures analyses of variance (ANOVA) were conducted on all quality of life and urinary outcome measures for all 31 patients at all time points. RESULTS: The median age of the study population was 66 (range 51-80). All men had clinical T1c-T2b prostate cancer. The Gleason score was < or =6 in 27/31 (87%). Median pretreatment PSA was 7.8 ng/ml (range 1.1-20.6). The mean score (and standard deviation) at T0, T1, T3, T6, and T12 for the FACT-P questionnaire are as follows: 140.5 (13.5), 132.7 (15.3), 137.2 (17.4), 140.1 (16.0), and 142.4 (15.3). For the global test across time, statistically significant differences were observed for the cumulative scores of FACT-P (p<0.0012). The decrease in HRQOL was most marked 1 month following PIB. Examination of the subscales within the FACT-P instrument demonstrated statistically significant changes over time for the following: physical well-being (PWB), functional well-being (FWB), and prostate cancer (PCS). By 3 months, all HRQOL measures had returned to near baseline. The mean score (and standard deviation) at T0, T1, T3, T6, and T12 for the IPSS questionnaire are as follows: 8.3 (5.5), 18.4 (8.0), 15.7 (7.4), 13.7 (7.4), and 10.2 (5.7). For the global test across time, statistically significant differences were observed for the IPSS scores (p<0.0001). The maximum increase in IPSS occurred 1 month following PIB. CONCLUSION: The results of this preliminary analysis suggest that clinically meaningful decreases in HRQOL, as measured by the FACT-P instrument, are evident within weeks after PIB. By 3 months, however, FACT-P scores return to near baseline levels. A validated instrument designed to measure urinary symptoms (IPSS) demonstrates that moderate to severe urinary symptoms persist for at least 3-6 months following PIB. One year following PIB, the scores on the FACT-P and IPSS questionnaires had returned to baseline.

A prospective quality-of-life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy.

PURPOSE: To prospectively assess the health-related quality of life (HRQOL) and changes in HRQOL during the first year after 3 different treatments for clinically localized prostate cancer. METHODS AND MATERIALS: Ninety men with T1-T2 adenocarcinoma of the prostate were treated with curative intent between May 1998 and June 1999 and completed a quality-of-life Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire before treatment (T0) and 1 month (T1), 3 months (T3), and 12 months (T12) after treatment. Forty-four men were treated with permanent source interstitial brachytherapy (IB), 23 received external beam radiotherapy (EBRT), and 23 men were treated with radical prostatectomy (RP). The mean age of the entire study population was 65.9 years (median 67, range 42-79). The mean pretreatment prostate-specific antigen level of the entire study population was 6.81 ng/mL (median 6.25, range 1.33-19.6). The Gleason score was