Fargo VA Health Care System

BACKGROUND: Fenfluramine and phentermine have been individually approved as anorectic agents by the Food and Drug Administration (FDA). When used in combination the drugs may be just as effective as either drug alone, with the added advantages of the need for lower doses of each agent and perhaps fewer side effects. Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million. METHODS: We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. RESULTS: Twenty-four women (mean [+/-SD] age, 44+/-8 years) were evaluated 12.3+/-7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right-sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical to those seen in carcinoid or ergotamine-induced valve disease. CONCLUSIONS: These cases arouse concern that fenfluramine-phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine-phentermine therapy should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above ~44°N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.

OBJECTIVE: To describe the quality of life (QOL) over time for adults with newly diagnosed high-grade gliomas and to examine the relationship between QOL and outcome data collected in three prospective cooperative group clinical trials. METHODS: The QOL study was a companion protocol for three Phase II high-grade glioma protocols. Five self-administered forms were completed by patients to assess QOL at study entry, 2 months, and 4 months after enrollment. RESULTS: QOL data were available for baseline, first, and second subsequent follow-up evaluations for 89%, 71%, and 69% of patients, respectively. A significant proportion of patients (47.1%) experienced impaired QOL (QOL < or = 50) in at least one measure at subsequent evaluations, whereas most patients (88%) with impaired QOL at baseline continued to have impaired QOL at subsequent evaluations. On multivariable analyses, baseline QOL measures were predictive of QOL at the time of follow-up. In addition, patients who underwent a gross total resection were much less likely to have impaired QOL (P = 0.006), were less likely to experience worsening depression (P = 0.0008), and were more likely to have improved QOL (P = 0.003) at their first follow-up evaluation. Changes in QOL measures over time were not found to be associated with survival in multivariable analyses that adjusted for known prognostic variables; variables that were independently associated with improved survival were better performance status (P < 0.001), younger age (P < 0.001), and greater extent of resection (P < 0.001). CONCLUSION: Baseline QOL was predictive of QOL over time. Gross total resection was associated with longer survival and improved QOL over time for patients with high-grade gliomas.

BACKGROUND: Since its introduction in 1999, West Nile virus has rapidly become the most common arboviral infection in North America. Little is known about the long-term clinical sequelae of West Nile virus infection. METHODS: A total of 49 patients with laboratory-confirmed West Nile virus infection were identified through state-based surveillance. Stratification for disease severity was based on hospitalization during the infection episode. Assessment occurred a mean of 13 months after diagnosis. Medical records were reviewed, and a complete neurologic examination was performed. Standardized surveys for quality of life, functional ability, fatigue, and depression were performed for all subjects. An extensive battery of neuropsychological tests was performed to assess cognitive function. RESULTS: Self-reported fatigue, memory problems, extremity weakness, word-finding difficulty, and headache were common complaints. Standardized survey data confirmed an overall sense of poor physical health, fatigue, depression, and moderate-to-severe disability in 24 (49%), 24 (49%), 12 (24%), and 4 (8%) patients, respectively. New tremor was seen or reported for 10 (20%) of the patients. Neuropsychological testing showed abnormalities of motor skills, attention, and executive functions. Univariate analysis of multiple risk factors did not identify any predictors of adverse outcomes. CONCLUSIONS: Multiple somatic complaints, tremor, and abnormalities in motor skills and executive functions are common long-term problems among patients who have had West Nile virus infection. Patients with milder illness are just as likely as patients with more-severe illness to experience adverse outcomes.

Benzodiazepine (BZD) abuse has reached epidemic levels and results in poor outcomes, particularly when combined with concomitant central nervous system depressants. BZDs are abused most commonly in combination with opioids and alcohol. Emergency department visits and related deaths have soared in recent years. In the absence of other medications or illicit substances, BZDs are rarely the sole cause of death. Prescription drug abuse has received more attention in recent years, yet much remains unknown about BZD abuse. BZDs have low abuse potential in most of the general population. A subset is at elevated risk of abuse, especially those with a history of a substance use disorder. Education, prevention, and identification are vital in reducing BZD abuse.

West Nile virus (WNV) was first recognized in the USA in 1999. We estimated the cumulative incidence of WNV infection in the USA from 1999 to 2010 using recently derived age- and sex-stratified ratios of infections to WNV neuroinvasive disease (WNND) and the number of WNND cases reported to national surveillance. We estimate that over 3 million persons have been infected with WNV in the USA, with the highest incidence rates in the central plains states. These 3 million infections would have resulted in about 780 000 illnesses. A substantial number of WNV infections and illnesses have occurred during the virus' first decade in the USA.

BACKGROUND: Few studies have reported the epidemiological characteristics of Haemophilus influenzae disease among adults. METHODS: Public health surveillance and hospital discharge data from Illinois were examined to determine the descriptive epidemiological characteristics and trends of invasive H. influenzae disease, and mortality data from Illinois were compared with data from several other states. RESULTS: During January 1996-December 2004, 770 cases of invasive H. influenzae disease were reported to the Illinois Department of Public Health (Springfield). The incidence of disease increased from 0.4 to 1.0 cases per 100,000 persons, including an increase of incidence in adults aged > or = 65 years from 1.1 to 3.9 cases per 100,000 persons. Nontypeable H. influenzae disease accounted for the greatest proportion of cases (35.8%-61.5%) in all but 1 age group. The number of cases of invasive nontypeable H. influenzae disease increased by 657%, from a low of 7 cases in 1996 to a high of 53 cases in 2004; as a proportion of annual cases, nontypeable H. influenzae disease increased from 17.5% in 1996 to 70.7% in 2004. Overall, the case-fatality rate was 12.7%, with the highest rate observed in persons aged > or = 65 years (20.6%). The case-fatality rate was similar for the hospital discharge database and for Indiana, Maryland, Oregon, and Wisconsin (range, 12.9%-18.2%). CONCLUSIONS: In Illinois, the incidence of invasive H. influenzae disease increased from 1996 to 2004, and its epidemiological characteristics changed from a disease predominantly found in children and dominated by serotype b to a disease predominantly found in adults and dominated by nontypeable strains.

OBJECTIVE: To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults. DESIGN: Overview of systematic reviews. DATA SOURCE: Five bibliographic databases were searched from January 2002 to March 2024. RESULTS: From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose-response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%-17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose-response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations. CONCLUSION: We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.

BACKGROUND: Stomatitis has been found to be a major dose-limiting toxicity from bolus 5-fluorouracil-based (5-FU) chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data which suggested that a chamomile mouthwash might ameliorate this toxicity, a prospective trial was developed to test chamomile in this situation. METHODS: A Phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered into the study at the time of their first cycle of 5-FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5-FU. In addition, each patient was randomized to receive a chamomile or placebo mouthwash thrice daily for 14 days. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There were 164 evaluable and well-stratified patients equally randomized to both treatment groups. There was no suggestion of any stomatitis difference between patients randomized to either protocol arm. There was also no suggestion of toxicity. Subset analysis did reveal unsuspected differential effects between males and females that could not be explained by reasons other than chance. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that chamomile could decrease 5-FU-induced stomatitis.

This study examined possible predictors of adjustment to breast cancer. Sixty-one women participated soon after they were diagnosed with Stage I or Stage II breast cancer. Measures were gathered at diagnosis and again 4 months later. Predictor variables included aspects of the disease and treatment process and reported coping behavior. The most consistent predictor of distress and, to a lesser extent, quality of life, was avoidant coping: women who reported more avoidant coping were more distressed. These data fit well with most previous research and suggest one way of identifying women who may be more at risk for special difficulties coping with the diagnosis of breast cancer.

BACKGROUND: Unlike many patients of the past, today's health-care users want to become more informed about their illnesses, and they want the most current information. The Internet has become a popular way to access current information, and since its introduction more people are turning to it to find medical information. Studies report that anywhere from 36% to 55% of the American population that use the Internet is using the Internet to research medical information, and these percentages have been rising. Cancer is 1 of the top 2 diseases about which people seek information on the Internet. Some studies have specifically asked whether breast cancer patients access the Internet for medical information; estimates range from 10% to 43% of breast cancer patients who use the Internet, with higher usage being associated with more education, greater income, and younger age. OBJECTIVE: To identify where breast cancer patients find medical information about their illness and to track changes over time, from active treatment to survivorship status. METHODS: Participants were 224 women who had been recently diagnosed with Stage I, Stage II, or Stage III breast cancer. Each woman was contacted approximately 8 months and 16 months after diagnosis and was asked about 10 different information sources they could have used to obtain information or support about their breast cancer. RESULTS: Eight months after diagnosis, the top 3 information sources used by women were books (64%), the Internet (49%), and videos (41%). However, at follow-up (16 months after diagnosis), the most frequently cited information source was the Internet (40%), followed by books (33%), and the American Cancer Society (17%). We found that women continued to use the Internet as a means of gathering information even after their treatment ended. Significant unique predictors of Internet use were more years of formal education and younger ages. Cancer stage was not a significant predictor of Internet use. CONCLUSIONS: Previous research has been mixed about the percentage of cancer patients who use the Internet to gather information about their illnesses. The results of the present study corroborate 2 other data sets of breast cancer patients, as just over 44% of the women reported using the Internet after diagnosis. Sixteen months after diagnosis, the percentage of women using the Internet dropped slightly, but other chief sources dropped sharply at that time. The Internet continues to play an important role for cancer survivors after medical treatment has ended, and health professionals can use this knowledge to provide their patients with Internet advice.

BACKGROUND: The current study was conducted to determine whether the addition of interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine (BCNU) improves time to disease progression or overall survival in patients with high-grade glioma. METHODS: Patients with anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation therapy plus BCNU as initial therapy. Subsequently, patients without tumor progression at the completion of radiation therapy were stratified by age, extent of surgery, tumor grade and histology, Eastern Cooperative Oncology Group performance status, and treating institution, and then were randomly assigned to receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3) plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks for a maximum of 6 cycles. RESULTS: Of the 383 patients enrolled in the study, 275 eligible patients were randomized. There was no significant difference with regard to time to disease progression or overall survival between the two groups. Patients receiving IFN-alpha experienced more fever, chills, myalgias, and neurocortical symptoms including somnolence, confusion, and exacerbation of neurologic deficits. Cox multivariate regression models confirmed known favorable prognostic variables including younger age, Grade 3 tumor (according to World Health Organization criteria), and greater extent of surgery. Cox and classification and regression tree analysis models also demonstrated that a normal baseline Folstein mini-mental status examination (MMSE) score was associated with better prognosis. CONCLUSIONS: IFN-alpha does not appear to improve time to disease progression or overall survival in patients with high-grade glioma and appears to add significantly to toxicity. The baseline MMSE score may serve as an independent prognostic factor and warrants further investigation.

BACKGROUND: Breast-feeding is the recommended method of infant feeding because it is clearly associated with health benefits for infants and their mothers. Yet, many women who initiate breast-feeding fail to meet their own personal goals or recommended standards for duration of breast-feeding. OBJECTIVE: To refine a Theory of Planned Behavior (TPB)-based structural model for explaining variability in breast-feeding intention and duration. METHOD: The study design was prospective, multicorrelational, and longitudinal. Out of the total sample of 635 women, 602 mothers of healthy, full-term infants provided complete datasets over the entire course of their breast-feeding experience and these datasets were used in the modeling analyses. Simultaneous multisample analysis of covariance structures was used to develop the model. RESULTS: The resulting TPB for Breast-Feeding (TPB-BrF) describes the rational, motivational processes of the original TPB, but reconfigures the relationships among them, for homemakers (TPB-BrF/H), women employed half-time or less (TPB-BrF/EL), and women employed more than half-time (TPB-BrF/EM). Mothers' early postpartum ratings of adequacy of milk supply and stimulus conditions of maternal education and breast-feeding knowledge were included in the TPB-BrF to better explain breast-feeding outcomes. Model complexity increased with employment effort. CONCLUSION: The TPB-BrF is a comprehensive, theoretically based, empirically verified model that can serve as a useful heuristic for understanding the personal motivational components of breast-feeding behavior.

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

OBJECTIVE: To compare health-related quality of life (HRQOL) measures in obese presurgery patients with and without binge-eating disorder (BED) and to investigate the relationship between a generic [short form-36 (SF-36)] and a disease-specific HRQOL measure [Impact of Weight on Quality of Life Questionnaire (IWQOL)] and measures of eating-related and general psychopathology. RESEARCH METHODS AND PROCEDURES: One hundred ten patients ages 19 to 62 years with a mean body mass index of 48.4 +/- 8.3 kg/m(2) who were evaluated for gastric bypass surgery were asked to fill out questionnaires assessing eating-related and general psychopathology (depression, self-esteem), as well as the two HRQOL questionnaires. BED was assessed by self-report. RESULTS: Nineteen (17.3%) patients met criteria for BED. Significant differences between patients with and without BED were found for four of the eight subscales of the SF-36-with effect sizes ranging from 0.44 to 0.75-and for the total score and three of the five subscales of the IWQOL-Lite-with effect sizes from 0.57 to 0.74. The mental composite score of the SF-36 as well as the IWQOL total score correlated significantly with the measures of psychopathology. DISCUSSION: This is the first study comparing the results of HRQOL measures in morbidly obese presurgery patients with and without BED. The results indicate that BED has a profound negative impact on HRQOL that exceeds the influence of obesity. Both HRQOL measures were able to reliably discriminate between patients with and without BED. Depression and self-esteem influenced HRQOL in a similar way as binge eating.

OBJECTIVE: The definition of night eating syndrome (NES) is inconsistent across various studies and literatures. The goal of the current descriptive study was to collect data on participants who were selected using broad criteria for nighttime eating. Researchers have cogently argued for consideration of wide ranges including "subsyndromal" cases before reifying diagnostic constructs prematurely. METHOD: One-hundred six participants with broadly defined nighttime eating problems were recruited through newspaper advertisements and were interviewed over the phone. The following instruments were administered: the Night Eating Questionnaire, the Night Eating Syndrome History and Inventory, the Eating Disorder Questionnaire, the Structured Clinical Interview for DSM-IV diagnoses and a Sleep Disorder Questionnaire. RESULTS: Thirty-one (29.2%) participants met the original criteria described by Stunkard et al. (Am J Med 1955;19:78) and only 14 (13.2%) participants met all of the most recent proposed criteria for NES (Birketvedt et al., JAMA 1999;282:657). The overlap between binge eating disorder (BED) and nighttime eating problems was modest in our sample with only 9 participants meeting current BED criteria. One half of our sample was obese. Regular nocturnal eating was reported by 57.5% of the participants. Dieting was not a frequent precursor or antecedent of nocturnal eating. However, self-reported current parasomnias were quite frequent in our sample. CONCLUSION: Our descriptive study confirms some of the observations made by other researchers. Nevertheless, nighttime eating is still an evolving concept that requires close collaboration between eating and sleep researchers.

In hereditary hemochromatosis (HH), increased intestinal iron absorption leads to the development of iron overload. To examine the abnormal regulation of iron absorption in this disorder, we analyzed mucosal iron kinetics in six patients with HH and in five normal subjects by using a compartmental model of intestinal iron absorption and systemic ferrokinetics. Subjects were given simultaneous oral and intravenous tracer doses of iron 59-labeled citrate and iron 55-labeled transferrin, respectively. Plasma and whole-body radioactive iron levels were then monitored serially during the next 2 weeks, and mucosal iron transport rate constants were estimated by non-linear least-squares fit of the model to these data. Iron absorption was inversely related to serum ferritin concentration in both normal subjects and patients with HH but was higher in relation to serum ferritin level among the latter (p less than 0.0002). Analysis of mucosal iron kinetics demonstrated a similar inverse relationship between the rate constant for mucosal iron uptake and serum ferritin among all subjects combined, but the mean uptake rate constant in patients with HH did not differ from that of normal subjects (p = 0.71). The mean rate constant for incorporation of iron into the mucosal storage pool in patients with HH also was comparable to that of normal subjects (p = 0.94). In contrast, the rate constant for transfer of mucosal iron to the plasma was higher in patients with HH than in normal subjects for any given serum ferritin level (p less than 0.0001), and the transfer rate constant accounted for 87% of the variability in iron absorption among all subjects. We conclude that the increased iron absorption in HH is mediated primarily by an increase in the rate constant for transfer of mucosal iron to the plasma.

Abstract BACKGROUND Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6‐month survival, response, and toxicity associated with a combination of gemcitabine, 5‐fluorouracil (5‐FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA). METHODS A 4‐week course included 1000 mg/m 2 gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25 mg/m 2 LV by intravenous push, and 600 mg/m 2 5‐FU by intravenous push after LV. RESULTS Forty‐two patients were enrolled in 6 months, 35 of whom had metastatic disease. Patients with biliary tract ACA included 24 with hepatic disease (19 patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4 with disease in the ampulla of Vater. All patients were evaluable and received a median of 4 courses of treatment (range, 1–21 courses). Commonly occurring severe toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea (four patients), fatigue (seven patients), thrombocytopenia (six patients), emesis (four patients), and diarrhea (four patients). Five partial responses (9.5%) occurred, 3 of which were sustained for ≥ 8 weeks. No treatment‐related deaths occurred. Thirty‐two patients had disease progression and 38 died after a median follow‐up of 20 months (range, 1.4–24 months). The median time to disease progression was 4.6 months (95% confidence interval [95% CI], 2.4–6.6%). The median survival period was 9.7 months (95% CI, 7–12%). CONCLUSIONS This combination regimen was manageable in patients with advanced biliary tract and gallbladder ACA. Of 42 patients, 24 (57%) survived ≥ 6 months, satisfying the primary end point of the trial. The length of survival suggested that gemcitabine, 5‐FU, and LV had benefit equivalent to gemcitabine alone. Cancer 2005. © 2004 American Cancer Society.

To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure. A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01). The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use. Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04). This association was even stronger when adjusted for differences in family history. None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04). Iron deficiency may protect against the development of febrile seizures.