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OBJECTIVE Home caregivers (eg parents) of pediatric patients with cancer with external central lines (CL) must carefully maintain this device to prevent complications. No guidelines exist to support caregiver skill development, assess CL competency, follow-up after initial CL teaching, and support progress over time. We aimed to achieve >90% caregiver independence with CL care within 1 year through a family-centered quality improvement intervention. METHODS Drivers to achieve CL care independence were identified using surveys and interviews of patient or caregivers, a multidisciplinary team with patient or family representatives, and piloting clinic return demonstrations (teach-backs). A family-centered CL care skill-learning curriculum, with a postdischarge teach-back program, was implemented using plan-do-study-act cycles. Patients or caregivers participated until independent with CL flushing. Changes included: language iterations to maximize patient or caregiver engagement, developing standardized tools for home use and for teaching and evaluating caregiver proficiency on the basis of number of nurse prompts required during the teach-back, earlier inpatient training, and clinic redesign to incorporate teach-backs into routine visits. The proportion of eligible patients whose caregiver had achieved independence in CL flushing was the outcome measure. Teach-back program participation was a process measure. Statistical process control charts tracked change over time. RESULTS After 6 months of quality improvement intervention, >90% of eligible patients had a caregiver achieve independence with CL care. This was sustained for 30 months postintervention. Eighty-eight percent of patients (n = 181) had a caregiver participate in the teach-back program. CONCLUSION A family-centered hands-on teach-back program can lead to caregiver independence in CL care.

Clinical pathways have the potential to improve complex clinical decision-making in cancer care. The authors implemented pathways with customized content to assist oncologists to select treatments, aiming for an on-pathway rate of 70%-85%. Treatment decisions were captured as on or off pathway, and metrics were shared monthly with users. Oncologists were categorized into quintiles based on on-pathway performance during the first 90 days of use. On-pathway rates were then calculated for days 91-360 (N = 121). Median on-pathway quintile rates varied from 50% to 100% in the initial 90-day period. During follow-up, median on-pathway rates shifted into the prespecified goal range for all groups. Clinical pathways resulted in greater uniformity in medical oncology practice. Monthly feedback about usage, familiarity with the electronic platform, and regular content updates are some factors that may influence on-pathway rates. Clinical pathways hold promise to manage unwarranted variation in cancer care.

The Accreditation Council of Graduate Medical Education mandates that all internal medicine residents gain exposure to internal medicine subspecialties including hematology and oncology. While many residents meet this criterion through inpatient oncology rotations, the current structure of many inpatient oncology rotations leaves little opportunity for formal education. We therefore designed a novel oncology curriculum consisting of one-page oncology teaching sheets to increase the number, breadth, and quality of formal teaching sessions on our resident inpatient oncology services. In order to evaluate the curriculum, we conducted pre- and post-intervention surveys of residents. From these surveys, we found that 72.2% of residents used the teaching sheets on their inpatient oncology rotation and that the teaching sheets led to an increase in the number of formal oncology teaching sessions (mean 3.4 ± 2.1 post-implementation vs 2.6 ± 2.0 pre-implementation, p = 0.008), the breadth of oncology topics taught (% reporting ≥ 5 topics; 26.1% vs 16.3%, p = 0.035), the proportion of residents reporting improvement in overall oncology knowledge (80.2% vs 62.4%, p = 0.012), and the proportion of residents reporting improvement in their ability to care for patients (70.8% vs 48.9%, p = 0.013). These results demonstrate that formal oncology teaching can be improved on inpatient oncology rotations through a simple and easily replicable oncology curriculum. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02055-6.

PURPOSE: The development of strategies to prevent or mitigate cancer treatment–related adverse events (AEs) is necessary to improve patient experience, safety, and cost containment. To develop a strategy to easily identify and mitigate AEs, we sought to understand the frequency and severity of those that resulted in hospitalizations. METHODS: We retrospectively characterized hospitalizations of ambulatory adult patients with solid tumor cancers within 30 days of chemotherapy administration using medical record data abstraction. Hospitalizations were categorized as caused by cancer symptoms, a noncancer medical condition, or a medical oncology treatment-related AE. Severity of the treatment-related AE hospitalization was rated using the National Patient Safety Agency risk assessment matrix scale. RESULTS: Between May and October 2016, 116 patients experienced 197 hospitalizations (per-patient mean, 1.7 AEs; range, 1 to 7 AEs). Sixty-six percent (n = 130) of hospitalizations were related to cancer symptoms, whereas 19.3% (n = 38) were treatment-related AE hospitalizations. The median length of stay of hospitalizations that resulted from an AE was 6 days (interquartile range, 3 to 9 days), and 36.8% had more than 1 AE. GI symptoms accounted for 48.1% of AEs, and neutropenic fever accounted for 11.1%. Sixty-one percent of treatment-related AE hospitalizations were characterized as moderate severity. CONCLUSION: Hospitalizations in patients with solid tumors as a direct result of their medical oncology care treatment are not uncommon. These findings argue for novel approaches, such as automated trigger tools, to identify and manage complications of medical oncology treatment before hospitalization is needed. Improved outpatient management of cancer symptoms may have a dramatic impact on hospitalizations for patients with cancer.

Objectives To determine whether slow gait speed increases the risk of costly long-term nursing home residence when accounting for death as a competing risk remains unknown. Design Longitudinal cohort study using proportional hazards models to predict long-term nursing home residence and subdistribution models with death as a competing risk. Setting Community-based prospective cohort study. Participants Older women (mean age 76.3) participating in the Study of Osteoporotic Fractures who were also enrolled in Medicare fee-for-service plans (N = 3,755). Measurements Gait speed was measured on a straight 6-m course and averaged over two trials. Long-term nursing home residence was defined using a validated algorithm based on Medicare Part B claims for nursing home–related care. Results Participants were followed until long-term nursing home residence, disenrollment from Medicare plan, death, or December 31, 2010. Over the follow-up period (median 11 years), 881 participants (23%) experienced long-term nursing home residence, and 1,013 (27%) died before experiencing this outcome. Slow walkers (55% of participants with gait speed

Biologic markers are becoming a key part of gerontological research, including their measurement at multiple intervals to detect changes over time. This report examined the feasibility and quality of 24-hr urine collection to measure neuroendocrine biomarkers in a community-based sample of older caregivers and non-caregivers. At each interview, participants were instructed on the correct method to collect and store the sample. As incentives, participants selected a day for urine collection within 5 days of the interview, received a reimbursement, and study staff travelled to their home to retrieve the specimen. Between 2008 and 2013, 256 participants were enrolled; all but two participants (99%) provided a baseline urine specimen, of which 93% were considered adequate. Urine collection and quality remained high over three annual follow-up interviews and did not vary by caregiver status or perceived stress level. Our results indicate that 24-hr urine collection is feasible in active, community-dwelling older adults.

2079 Background: Clinical oncology pathways aim to support clinical decision-making and reduce unwarranted practice variation across an enterprise. The Dana-Farber Cancer Institute (DFCI) implemented web-based oncology pathways with DFCI-customized content in each disease center and at each of its satellites. Our pre-specified aim was an on-pathway rate of 70-85%. Methods: Treatment decisions were electronically captured as on- or off- pathway. Monthly metrics about usage and on-pathway rate were shared with users on a monthly basis. Physicians were categorized into quintiles based on the calculated on-pathway performance during the first 90 days of each individual’s use of the platform. On-pathway rates were then calculated for days 91-360 to study changes in behavior over time. Physician and practice factors were examined to determine any differences by initial on-pathway quintile classification. Results: 122 physicians were eligible for inclusion in this analysis (minimum 5 navigations in each study period). On-pathway rates showed significant variability in the initial 90-day period: quintile 1 median 100%, quintiles 2-4 80.2%, and quintile 5 50% (Table). In the follow-up period, median on-pathway rates shifted into the pre-specified goal range for all groups. Physicians in quintiles 1 or 5 of initial on-pathway rate were more likely to have fewer total navigations than were physicians in quintiles 2-4 (p=0.003). While no other physician or practice characteristic differed significantly by on-pathway rate group, physicians in the first or last quintile were more likely to be in an academic setting, have a PhD, or navigate fewer pathways. Conclusions: Over time, the deployment of a web-based clinical pathways program resulted in greater uniformity in physician practice, based on on-pathway rate. Familiarity with the pathways platform and its navigation, monthly feedback about usage, and evolution of content over time are some factors that might have played a role. [Table: see text]

The rapid pace of technological advancements and the corresponding societal innovations and adaptations make it difficult to predict how teaching epidemiology will look in the coming decades. We discuss changes in the teaching of epidemiology that are currently unfolding. First, typical epidemiology curricula often lack formal instruction in important components of causal thinking, such as the formulation of well-defined research questions. We address gaps related to causal thinking, communication about our science, and interpretation of study results, and we make suggestions of specific content to close such gaps. Second, digital technology increasingly influences epidemiology instruction. We discuss classroom and online teaching modalities in terms of challenges and advantages.

Receipt of chemotherapy in the last 14 days of life is a measure of potential overuse of care. Specific measures defining appropriate end-of-life use of oral agents have not yet been described, and little is known about prescribing patterns.We conducted an exploratory analysis of 371 patients at Dana-Farber Cancer Institute who were covered by the Blue Cross Blue Shield of Massachusetts pharmacy benefit and died during 2012 to 2013. We analyzed processed claims as a surrogate for chemotherapy administration. We compared oral with parenteral chemotherapy claims in the last 6 months of life.In the last 6 months of life, 294 patients (79%) had chemotherapy claims, including 81 (22%) prescribed an oral agent; 20 patients had claims for oral chemotherapy in the last 30 days of life. For eight patients (40%), this was the initial start of that oral agent. In the last 14 days of life, only 23 patients had chemotherapy claims, including six patients prescribed an oral agent.The collection of oral chemotherapy use data through insurance claims was feasible. Processed claims for chemotherapy, including oral, sharply declined during the last 30 days of life, consistent with a shift to palliative management. These results highlight the need for a more comprehensive analysis of oral chemotherapy prescribing patterns and development of specific measures to define the appropriate use of oral chemotherapy at the end of life.

Purpose of the Study: Depressi ve symptoms and disability each increase the risk of the other, yet few studies have examined reciprocal associations between these conditions in a single study, or over periods longer than 3 years. These associations may differ in older caregivers due to chronic stress, health characteristics, or factors related to caregiving. Design and Methods: Structural equation models were used to in vestigate relationships between depressive symptoms and disability over 3 interviews spanning 6 years among 956 older women (M = 81.5 years) from the Caregiver Study of Osteoporotic Fractures. Results were evaluated separately for 611 noncaregivers and 345 caregivers to a relative or friend. Results: In noncaregi vers, more depressive symptoms significantly predicted greater disability, whereas greater disability predicted increased depressive symptoms at the next interview in age-adjusted models. In contrast, there was not a significant relationship between depression and disability in either direction for caregivers. Further adjustment for body mass index and medical condition variables did not change these relationships. Implications: Caregi vers did not exhibit longitudinal or reciprocal relationships between depressive symptoms and disability observed in noncaregivers. It is possible that older women caregivers are buffered by better physical condition or social interactions related to caregiving activities.

Our aim was to assess the association of perceived racism with type 2 diabetes, and the possible mediating influence of diet and BMI. The Black Women’s Health Study, a follow-up of 59,000 African-American women, began in 1995. Over 16 years 5344 incident cases of diabetes occurred during 576,577 person-years. Cox proportional hazards models were used to estimated HRs and 95% CIs for categories of ‘everyday racism’ (interpersonal racism in daily life) and ‘lifetime racism’ (reporting ever treated unfairly due to race with respect to police, housing or work) and incident type 2 diabetes. Models were adjusted for age, questionnaire cycle, marital status, socioeconomic status, education, family history of diabetes, physical activity, alcohol use and smoking status, with and without inclusion of terms for dietary patterns and adult BMI. Compared with women in the lowest quartile of exposure, women in the highest quartile of exposure to everyday racism had a 31% increased risk of diabetes (HR 1.31; 95% CI 1.20, 1.42) and women with the highest exposure to lifetime racism had a 16% increased risk (HR 1.16; 95% CI 1.05, 1.27). Mediation analysis estimated that BMI accounted for half of the association between either the everyday or lifetime racism measure and incident diabetes. Perceived everyday and lifetime racism were associated with increased risk of type 2 diabetes in this cohort of African-American women and appear to be at least partly mediated by BMI.

The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and α-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis. J. Med. Virol. 86:1877–1885, 2014. © 2014 Wiley Periodicals, Inc.

e14172 Background: Management of Immune checkpoint inhibitors (ICIs) associated irAEs requires accurate diagnosis and severity measurement. However, outside of clinical trials, there is no clear definition of irAEs to guide treatment. Methods: We established a dedicated immune toxicity inpatient service (ITox) for patients admitted with irAEs using institution-developed guidelines adapted from NCCN and ASCO. We developed definitions for ICI associated hepatitis, colitis and pneumonitis and created algorithms for defining an irAEs as definite, likely, possible, or unlikely. Algorithm fields were completed twice, by two independent reviewers including medical oncology specialists and toxicity specialists (a pulmonologist or gastroenterologist) to evaluate the accuracy of the algorithm in defining irAEs. Results: From June to November 2018, 65 patients were admitted to iTox with suspected irAEs. Various cancers patients treated with ICI were included; with lung and head and neck cancers the most common (36.9%). Pembrolizumab was the most common ICI (47.7%). ICI in combination with non-checkpoint inhibitor treatment was used in 23 (37.7%) and concurrent radiation therapy in 5 patients (7.7%). Forty (71.4%) patients discontinued ICI due to toxicity. Fifty-one patients were evaluable with irAEs: colitis (19); pneumonitis (24) and hepatitis (8). Multiple irAEs were reported in 17 patients. When applied to clinical cases, our algorithms generated a toxicity definition in 63% of cases, with which reviewers agreed most of the time (84-100%) (Kappa 0.7-1.0). Concordance between the two reviewers was 75-87% (Kappa 0.55-0.82) (Table). Conclusions: Our algorithms generated irAEs definitions with fair inter-rater reliability. These findings have real-world implications; accurate diagnosis of irAEs is essential for proper management. Defining irAEs outside the clinical trial context remains an important challenge. [Table: see text]

Aim Subjects positive for antibody to hepatitis B core antigen (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are considered to have occult hepatitis B virus (HBV) infection. The aim of this study was to determine the impact of occult HBV infection on aggravation of the clinical course in hepatitis C virus (HCV) carriers.

A majority of patients with poor-prognosis cancer express a preference for in-home death; however, in-hospital deaths are common.We sought to identify characteristics associated with in-hospital death.Case series.Commercially insured patients with cancer who died between July 2010 and December 2013 and who had at least two outpatient visits at a tertiary cancer center during the last six months of life.Patient characteristics, healthcare utilization, and in-hospital death (primary outcome) were ascertained from institutional records and healthcare claims. Bivariate and multivariable analyses were used to evaluate the association of in-hospital death with patient characteristics and end-of-life outcome measures.We identified 904 decedents, with a median age of 59 years at death. In-hospital death was observed in 254 patients (28%), including 110 (12%) who died in an intensive care unit. Hematologic malignancy was associated with a 2.57 times increased risk of in-hospital death (95% confidence interval [CI] 1.91-3.45, p 0.001), and nonenrollment in hospice was associated with a 14.5 times increased risk of in-hospital death (95% CI 9.81-21.4, p 0.001). Time from cancer diagnosis to death was also associated with in-hospital death (p = 0.003), with the greatest risk among patients dying within six months of cancer diagnosis. All significant associations persisted in multivariable analyses that were adjusted for baseline characteristics.In-hospital deaths are common among commercially insured cancer patients. Patients with hematologic malignancy and patients who die without receiving hospice services have a substantially higher incidence of in-hospital death.

Purpose: The prevalence and severity of pain have not been well described among oncology patients in ambulatory care. To better understand the burden of pain among patients with advanced cancer, we examined the prevalence of pain reported during office and treatment visits. Methods: A retrospective study of 4,014 patients with advanced disease (stage 4 at diagnosis or metastatic progression) who completed an ambulatory visit between 2004 and 2006 was conducted at a comprehensive cancer center in Boston, Massachusetts. Results: At their first visit during the study period, 74% of patients reported no pain (0 score); 12%, low pain (1 to 3 score); 9%, moderate pain (4 to 6 score); and 5%, severe pain (7 to 10 score). The prevalence of pain was highest among patients who wereyoungerthan60yearsofage,werenonwhite,didnotspeak English as their primary language, or were covered by Medicaid, received free care, or paid their own health care costs. Patients with thoracic, breast, and head and neck cancers had higher pain scores than those with other diseases. Pain was reported more frequently among patients whose diagnosis or metastatic progression occurred less than 3 months before the reported pain score. In multivariable regression analysis, age, race, cancer type, and time since diagnosis/progression were identified as important factors associated with severe pain. Conclusion: Younger age, minority race, and recent onset of advanced disease are associated with severe pain among patients with cancer. Recognizing these high-risk groups could inform targeted interventions to address pain care in ambulatory patients with advanced cancer.

BACKGROUND: Although pain is common among patients with advanced cancer, little is known about longitudinal variability in pain intensity. For this report, the authors examined variability in pain intensity over 24 months among ambulatory patients with advanced stage cancers, associations between patient characteristics and within-patient pain variability, and the relation of pain variability to overall survival. METHODS: The sample comprised 949 patients with solid tumors who received care and reported pain scores in at least 3 different months within 24 months of their initial stage IV diagnosis during the period from 2004 to 2006. Pain intensity was measured using a scale ranging from 0 (no pain) to 10 (worst pain). Pain variability was defined as the standard deviation of the maximum monthly pain scores and was dichotomized at the 50th percentile into high and low variability groups. RESULTS: Considerable between-patient differences in pain variability (range, 0-5.77) were observed. Nonwhites, patients with a stage IV cancer diagnosed within the previous 3 months, and those with moderate or severe pain at baseline were more likely to experience high pain variability. Although patients with head and neck cancer generally had the highest pain variability, the intensity of their pain typically decreased over the disease course. High pain variability with worsening pain trajectory was associated with increased risk of death. CONCLUSIONS: Longitudinally, pain intensity was highly variable among patients with stage IV cancer. Minority patients, newly diagnosed patients, patients with head and neck cancer, and patients with moderate or severe pain at baseline were at higher risk of large fluctuations in pain intensity. Cancer 2012. © 2012 American Cancer Society.

Context Pain is common among patients with advanced cancer despite the dissemination of clinical pain care guidelines. Objectives We sought to assess the quality of pain care among patients with advanced disease. Methods We reviewed the records of 85 adult ambulatory patients with advanced breast, lung, and gastrointestinal cancer treated in 2004–2006. Patients' screening pain intensity scores were at least 7 of 10. Nurse reviewers completed medical record reviews of care rendered at the index visit and over the subsequent 30 days based on the 2004 National Comprehensive Cancer Network pain guideline. An expert panel then rated the quality of the evaluation, treatment, and overall pain care. We used a multivariable model to analyze guideline compliance and resolution of severe pain. Results Among advanced cancer patients with severe pain, clinicians adjusted pain medications only half the time and made few timely referrals for pain-related consultations. By 30 days after the index visit, 34% of patients continued to report severe pain. The expert panel judged the overall quality of pain care as "fair" or "poor" in about two-thirds of cases because more timely and effective intervention could have reduced the severity and duration of pain. Resolution of severe pain was associated with adjustment of pain medications at the index visit (adjusted odds ratio 3.8, 95% CI 1.3–10.6). Conclusion There is room for improvement in the pain care of patients with advanced cancer. Additional research is needed to understand the reasons for poor performance.

Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (≤ 30 IU/l) accompanied by normal platelet counts (≥ 15 x 10(4)/µl); these individuals show milder disease activity and slower progression to cirrhosis. This study aimed to elucidate the characteristics of HCV carriers with PNALT using serum proteomics. The first group of subjects, who underwent clinical evaluation in the hospital, consisted of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1) patients. The second group of subjects was part of a cohort study on the natural history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2) patients. Affinity bead-purified serum protein was subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Serum proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from 1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among these peaks, a 1738-m/z peak protein was identified as a fragment of complement component 4 (C4) and correlated significantly with serum C4a concentrations as determined by enzyme immunoassay. Serum C4a levels were also significantly higher in the PNALT-2 group compared to the CHC-2 group and healthy volunteers. Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with transaminase levels, but not with other biochemical tests, HCV core antigen levels, peripheral blood cell counts or serum hepatic fibrosis markers. This study indicates that host factors such as C4a not only differ between HCV carriers with PNALT and CHC, but that proteomic approaches could also contribute to the elucidation of factors in PNALT as more differences are discovered.

BACKGROUND: Pain is common among cancer patients.OBJECTIVE: To characterize the incidence of severe pain among newly diagnosed patients with stage IV cancer in ambulatory care.METHODS: A retrospective cohort of 505 ambulatory oncology patients with newly diagnosed stage IV solid tumours at a comprehensive cancer centre (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) was followed from January 1, 2004, to December 31, 2006. Pain intensity scores were extracted from electronic medical records. The incidence of severe pain was calculated using the maximum monthly pain scores reported at outpatient visits.RESULTS: Of the 505 patients included in the present study, 340 (67.3%) were pain-free at the initial visit, 90 (17.8%) experienced mild pain, 48 (9.5%) experienced moderate pain and 27 (5.4%) experienced severe pain. At least one episode of severe pain within one year of diagnosis was reported by 29.1% of patients. Patients with head and neck, gastrointestinal and thoracic malignancies were more likely to experience severe pain compared with patients with other types of cancer (52.6%, 33.9% and 30.5%, respectively). In the multivariable model, patients whose primary language was not English (OR 2.90 [95% CI 1.08 to 7.80]), patients who reported severe pain at the initial visit (OR 9.30 [95% CI 3.72 to 23.23]) and patients with head and neck (OR 10.17 [95% CI 2.87 to 36.00]) or gastrointestinal (OR 4.05 [95% CI 1.23 to 13.35]) cancers were more likely to report severe pain in the following year.CONCLUSIONS: The incidence of severe pain was high in ambulatory patients with newly diagnosed stage IV cancer.

Item does not contain fulltext OBJECTIVE: To understand the extent to which hospitalized patients participate in their care, and the association of patient participation with quality of care and patient safety. DESIGN: Random sample telephone survey and medical record review. SETTING: US acute care hospitals in 2003. PARTICIPANTS: A total of 2025 recently hospitalized adults. MAIN OUTCOME MEASURES: Hospitalized patients reported participation in their own care, assessments of overall quality of care and the presence of adverse events (AEs) in telephone interviews. Physician reviewers rated the severity and preventability of AEs identified by interview and chart review among 788 surveyed patients who also consented to medical record review. RESULTS: Of the 2025 patients surveyed, 99.9% of patients reported positive responses to at least one of seven measures of participation. High participation (use of >4 activities) was strongly associated with patients' favorable ratings of the hospital quality of care (adjusted OR: 5.46, 95% CI: 4.15-7.19). Among the 788 patients with both patient survey and chart review data, there was an inverse relationship between participation and adverse events. In multivariable logistic regression analyses, patients with high participation were half as likely to have at least one adverse event during the admission (adjusted OR = 0.49, 0.31-0.78). CONCLUSIONS: Most hospitalized patients participated in some aspects of their care. Participation was strongly associated with favorable judgments about hospital quality and reduced the risk of experiencing an adverse event. 01 juni 2011

e18815Background: Developing strategies to prevent or minimize cancer treatment-related adverse events (AEs) is a priority for value and patient safety. To develop a strategy for easier identificat...

The overall mortality of patients infected with hepatitis C virus (HCV) has not been fully elucidated. This study analyzed mortality in subjects positive for antibody to HCV (anti-HCV) in a community-based, prospective cohort study conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning in 1995, 1125 anti–HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005. Cause of death was assessed by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia-negative) were considered as having had a prior HCV infection and were classified as HCV noncarriers. Among the anti–HCV-positive subjects included in the analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths in the HCV carrier group and 55 in the noncarrier group. The overall mortality rate was higher in HCV carriers than in noncarriers, adjusted for age and sex (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95% confidence interval, 2.58-13.7), the rates of other causes of death did not differ between HCV carriers and noncarriers. Among HCV carriers, a higher level of HCVcAg (≥100 pg/mL) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality. Conclusion: The presence of viremia increases the rate of mortality, primarily due to liver-related death, among anti–HCV-seropositive persons in Japan. (HEPATOLOGY 2009.)

The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I noncarriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 71, respectively, p=0.005), soluble interleukin-2 receptor-alpha (477 vs. 623 pg/mL, p=0.0008) and soluble CD30 (34 vs. 46 U/mL, p=0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 microg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk.

The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection.The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed.No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level.The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers.

Documented treatment rates for Hepatitis C virus (HCV) infection are low. Within this cohort of HCV-infected patients (N = 373), participants who were not actively injecting drugs or not co-infected with HIV were most likely to initiate HCV treatment. Persons of white race and HIV-infected participants with a CD4 count above 200 were also more likely to have initiated HCV treatment. We defined five factors as potentially modifiable, and found almost all (90%) of the cohort had at least one such factor. Participants with more than one of these factors were least likely to initiate treatment. The proportion of patients receiving treatment increased as their number of modifiable risk factors decreased (p < 0.01, for trend). Focused strategies to overcome these potentially modifiable factors may be indicated to increase HCV treatment in affected populations.

BACKGROUND Ongoing substance use is a potential confounder for immunological studies on hepatitis C virus (HCV), but there is little in the literature regarding the effects of injection drug use (IDU) or alcohol on HCV-specific immune responses. We wanted to determine whether IDU or alcohol affected immune responses in HCV-infected and human immunodeficiency virus (HIV)/HCV coinfected subjects. METHODS Eight-four subjects with HIV/HCV and 57 with HCV were classified as either injection drug users, drinkers, or nonusers based on questionnaire results. Immune responses were studied with enzyme-linked immunosorbent spot assay for interferon (IFN)- gamma , interleukin (IL)-10, and tumor necrosis factor (TNF)- alpha against HCV proteins Core, NS3, and NS5 and recall antigens. RESULTS Subjects with HIV/HCV, in aggregate, had significantly lower HCV-specific IFN- gamma and TNF- alpha responses than subjects with HCV. However, HIV/HCV injection drug users had HCV-specific IFN- gamma and IL-10 responses that were similar to those of HCV injection drug users and were significantly higher than in nonusers with HIV/HCV. Conversely, subjects who drank alcohol had similar immune responses to those who were abstinent, among both subjects with HIV/HCV and subjects with HCV. CONCLUSIONS Studies that examine IFN- gamma or IL-10 immune responses in HIV/HCV-coinfected or HCV-infected persons need to consider current IDU. Alcohol, at levels consumed in this cohort, does not appear to have as much of an effect on antigen-specific immune responses.

Early detection of HCC increases the potential for curative treatment and improves survival. To facilitate early detection of HCC, this study sought to identify novel diagnostic markers of HCC using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS) ProteinChip technology. Serum samples were obtained from 153 patients with or without HCC, all of whom had been diagnosed with HCV-associated chronic liver disease. To identify proteins associated with HCC, serum samples were analyzed using SELDI-TOF/MS. We constructed an initial decision tree for the correct diagnosis of HCC using serum samples from patients with (n = 35) and without (n = 44) HCC. Six protein peaks were selected to construct a decision tree using this first group. The efficacy of the decision tree was then assessed using a second group of patients with (n = 29) and without (n = 33) HCC. The sensitivity and specificity of this decision tree for the diagnosis of HCC were 83% and 76%, respectively. For a third group, we analyzed sera from seven patients with HCC obtained before the diagnosis of HCC by ultrasonography (US) and from five patients free of HCC for the past 3 years. Use of these diagnostic markers predicted the diagnosis of HCC in six of these seven patients before HCC was clinically apparent without any false positives. Conclusion: Serum profiling using the SELDI ProteinChip system is useful for the early detection and prediction of HCC in patients with chronic HCV infection. (HEPATOLOGY 2007;45:948–956.)

We investigated the effects of polymorphisms in interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha on the natural course of hepatitis C virus (HCV) infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV RNA. In HCV RNA-positive individuals with at least four annual alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding IL-10 (-1082, -819, -592) or TNF-alpha (-308, -238) and HCV clearance, ALT abnormalities, or serum level of type IV collagen 7S, a marker of hepatic fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV RNA clearances or ALT abnormalities. Serum levels of type IV collagen 7S, however, were significantly higher in individuals with an A at position -238 or -308 in the TNF-alpha gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in IL-10 or TNF-alpha expression are not associated with alterations in HCV clearance or ALT levels, TNF-alpha polymorphisms may be associated with hepatic fibrosis.

We evaluated the utility of alanine aminotransferase (ALT) measurements in predicting the incidence of hepatocellular carcinoma (HCC) in a cohort of 667 adults with chronic hepatitis C virus (HCV) infection from a community-based population in Japan, between 1994 and 2003. Cox proportional hazards regression analysis was used to describe the relationship between prediagnostic levels of ALT and the rate of HCC, after adjusting for age and gender; hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained. Over an average of 8 years of follow-up, 52 HCC cases were identified. A significant association between a 20 IU/L difference in higher ALT level and subsequent HCC incidence was observed (HR = 1.2; 95% CI: 1.1, 1.3). An abnormal ALT level (≥35 IU/L) increased the HCC rate by 4-fold compared to a normal ALT level (HR = 4.1; 95% CI: 2.1, 8.0). Among 551 subjects with at least 4 repeated measurements of ALT, those with persistently abnormal ALT levels (n = 118) had a strong, significantly increased HCC rate compared to those with persistently normal ALT levels (n = 296) (HR = 23.2; 95% CI: 3.0, 178.5). This study demonstrates that elevated ALT levels, measured on an average of 8 years before HCC diagnosis, predict an increased rate of HCV-associated HCC in a community-based population and that utilizing serial measurements to identify persistent ALT abnormality may be useful in determining HCC risk. © 2006 Wiley-Liss, Inc.

Type 1 immunity appears to be diminished in healthy Japanese carriers of human T-lymphotropic virus type I (HTLV-I), but type 2 status remains undetermined. To further examine the subclinical effect of HTLV-I on host immunity, we measured serum antibodies to the Epstein-Barr virus (EBV) in 415 healthy Japanese adults to broadly characterize type 1 status. Levels of the type 2 biomarkers total immunoglobulin E (IgE), soluble CD23 (sCD23), and soluble CD30 (sCD30) were assessed in 167, 142, and 135 of these subjects, respectively. We analyzed the association of HTLV-I with levels of each serum marker using linear and logistic regression. Altered EBV antibody profiles that are consistent with deficient type 1 immunity were more prevalent in HTLV-I carriers than non-carriers (odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.5-5.3). Carriers also had 45% lower total IgE levels (P = 0.04) than non-carriers. In contrast, HTLV-I infection was not significantly associated with elevated levels of sCD23 or sCD30. These observations are contrary to our expectation of elevated type 2 biomarkers among carriers. We conclude that in this population, healthy carriers of HTLV-I may have subclinical deficiencies in both type 1 and type 2 immunity, and that type 1 and type 2 immunity are not necessarily reciprocal in persons with subclinical immune dysregulation.

Summary. A new immuno-radiometric assay (IRMA) to detect hepatitis C virus (HCV) core antigen (HCVcAg) has been developed. The aim of the present study was to investigate the sensitivity and specificity of this IRMA to measure HCV antigenemia, based on the detection of HCV RNA as the gold standard, and to assess the utility of the IRMA in a community-based population. Anti-HCV positive residents in a hyperendemic area of HCV infection in Japan were studied. Serum levels of HCVcAg were measured using IRMA, and the presence of HCV RNA was determined by a qualitative reverse transcription-polymerase chain reaction (RT-PCR) assay. The sensitivity and the specificity of the IRMA were 96.4 and 100%, respectively. The sensitivity of the IRMA was similar between serological HCV group I (HCV genotypes 1a and 1b) (97.6%) and group II (HCV genotypes 2a and 2b) (94.0%). There was a strong correlation between serum HCVcAg level and HCV-RNA measured by a quantitative RT-PCR (r = 0.832, P

To investigate whether female offspring of preeclamptic pregnancies have higher blood pressure, lower height, higher body mass index (BMI), and later age at menarche compared with offspring of normotensive pregnancies.Questionnaire information on age at menarche and measurements of blood pressure, height, and weight were collected among 4096 Norwegian girls 13-19 years old. Individual linkage to perinatal data registered at the national Medical Birth Registry allowed us to study the relationship of preeclampsia in the mother with adolescent blood pressure, body size, and age at menarche of daughters.Maternal preeclampsia was associated in the female offspring with higher systolic (2.9 mm Hg difference, P.001) and diastolic (1.7 mm Hg difference, P =.001) blood pressure during adolescence and higher weight (3.4 kg difference, P.001) and BMI (22.6 versus 21.5, P.001). After adjustment for adolescent BMI, the difference in systolic blood pressure was attenuated from 2.9 to 1.7 mm Hg (P =.017), and from 1.7 to 0.9 mm Hg (P =.08) for diastolic blood pressure.Intrauterine exposure to preeclampsia was associated with increased adolescent blood pressure. The association may be causally related to adult hypertension but could also be confounded by higher BMI during adolescence.

Sexual transmission of human T cell lymphotropic virus type 1 (HTLV-1) is considered to be an important route of infection in adults. However, no direct evidence has been reported that supports this observation. To address this issue, sequence variations of the gp46 (envelope)-coding region of HTLV-1 were determined in 13 patients infected with HTLV-1 who experienced seroconversion and in their spouses. Twenty-two nucleotide changes that were different from the reference sequence of lambdaATK-1 were identified. However, the gp46 sequences found were identical within each married couple. HTLV-1 proviral DNA loads measured in 11 of these couples varied from 10 to 3430 copies per 10(5) PBMC, and the proviral DNA loads of spouses often differed. This study provides the first genetic confirmation of the transmission of HTLV-1 from a carrier spouse to his/her partner. The findings also suggest that host-related factors play a more important role than do virus-specific factors in determining HTLV-1 proviral DNA load.

e18222 Background: Percutaneous lines and drains provide a less invasive alternative to operative procedures for patients with cancer. We categorized outcomes for placements among solid tumor patients hospitalized on the medical oncology services of a tertiary care academic center. Methods: Consecutive cases (n=71, Mar-Sept 2016) were identified by electronic medical record orders for non-vascular lines and drains placed in solid tumor patients hospitalized on medical oncology services and confirmed by retrospective chart review. Percutaneous nephrostomy tubes, pleurx catheters (abdominal and thoracic), gastrojejunostomy/gastric tubes, biliary drains, and wound/abscess drains were included. Retrospective chart review was used to categorize 30-day outcomes including those deemed related or possibly related to the placement that resulted in a phone call, office visit, ED evaluation, or hospital readmission. Results: Mean age at placement was 62 years and 53% of patients were female. All patients had metastatic tumor. The majority of patients had an Eastern Cooperative Oncology Group Performance Status of 3-4 (63.4%). Patients with gastrointestinal, gynecological and genitourinary malignancies required more procedures than all other tumor types combined. The 30-day mortality rate following line and drain placement was 32.4%. Of these deaths, 43.5% occurred prior to discharge and 30.4% occurred within two weeks. 40.8% of patients required ED evaluation or hospital readmission and 29.6% of patients required an office visit or phone call within 30 days. Conclusions: Although percutaneous interventions are generally safe and minimally invasive, there is a high 30-day mortality rate associated with line and drain placement among hospitalized patients with advanced cancer. Among patients who expired, over forty percent of deaths occurred during the index hospitalization, suggesting placements are occurring at the end of life, may potentially reflect overuse and may represent a missed opportunity to address goals of care. [Table: see text]

175 Background: Teaching patients and caregivers to manage a Peripherally Inserted Central Catheter (PICC) line placed during hospitalization is essential to successful outpatient transitions. The aim was to improve written care instructions at hospital discharge (CIHD) given to solid tumor oncology patients with new PICC lines by creating an electronic template in the electronic health record. Methods: Inpatients with newly placed PICC lines discharged from the physician assistants' (PA) oncology teams at Brigham and Women's Hospital were identified through PICC team consult lists. We identified 9 elements of complete line care, modeled on National Quality Forum discharge metrics, to include in a template for PICC line care instructions at discharge. PAs received instruction on template use at their weekly meeting. A retrospective chart review of CIHD (February 19, 2016 and October 13, 2016) was performed. Results: A total of 47 cases were reviewed, 19 cases Pre-introduction and 28 cases Post. Before introduction of the template, 74% of cases lacked PICC care instructions (including 13 cases with no mention of the PICC line), 26% had incomplete care instructions, and none had full instructions. Following the intervention, 64% still lacked care instructions (16 cases with no mention of the PICC line), 21% had incomplete care instructions, and 4 patients (14%) had full instructions. Only those CIHD that used the template had complete care instructions. A c-chart demonstrated special cause variation following the intervention but the process was chaotic. Conclusions: The introduction of a template for PICC care instructions led to modest improvement in the number of patients discharged with full instructions. This project highlights the limitations of solutions that incorporate technical solutions but only weak adaptive ones. The next phase of our work will introduce human factors interventions (e.g. automation and forcing functions) to improve the success rate of this critically important function. [Table: see text]

Objective: Walking speed is an important marker of functionality that is measured over courses of varying lengths, but it is unclear if course length affects measured pace. Method: A total of 136 older adults completed two consecutive trials each of 3-m and 6-m walking courses, the order of which was randomly assigned. We calculated concordance correlation coefficients (CCC) and created Bland–Altman plots to evaluate the relationship between the two course distances. Results: Average walking speed was faster for the 6-m course and the second trial of each course. There was high concordance between the first and second trials for both the 3-m and 6-m courses. Discussion: The 3- and 6-m courses had excellent test–retest reliability and faster walking speed in later than earlier trials. Higher concordance between courses for later trials suggests the utility of practice trials and adjusting for course length when combining walking speed measurements between different course lengths.

The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and α-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis.

Latent-class analysis was used to evaluate the usefulness of markers of hepatitis C virus (HCV) infection in characterizing the true, underlying infection in a community-based Japanese population. Antibodies to HCV were detected in 24%, HCV RNA in 22%, and HCV core protein in 19% of stored serum samples from 372 adults. A 2-class model suggested that positive results for any 2 virus markers defined the current HCV infection class, with an estimated prevalence of 22% (95% confidence interval, 18%‐26%). The sensitivity for detection of current HCV infection was highest for anti-HCV (97%) and was more moderate for HCV RNA (91%) and HCV core protein (85%). The specificity for each marker was 96%. In general, the association between demographic factors and current HCV infection status was strengthened by use of latent-class analysis that combined data for markers of HCV infection, when compared with results of logistic regression analysis for each marker separately. Hepatitis C virus (HCV) is an etiologic factor for both chronic hepatitis and hepatocellular carcinoma [1]. HCV infection is distributed worldwide, and population seroprevalences, as measured by the detection of antibodies to HCV, are within the range 0.5%–2.0% [1]. Since anti-HCV does not discriminate between current infection and resolved infection, methods to detect the virus can assist the classification of HCV infection status into current, resolved, or never infected. Detection of either viral RNA or core protein is indicative of current infection. Elevation of alanine aminotransferase (ALT) is a marker for hepatocyte damage or death that may be attributed to HCV infection. Many serologic surveys either measure anti-HCV alone or include methods to detect viral RNA or core protein only in anti-HCV–positive serum samples. The rationale for this approach may be due to the special handling required for the blood specimens, the high cost of the assays, or the difficulty in performing the assays. Moreover, measure

Twenty-three human T lymphotropic virus type I (HTLV-I) seroconverters were identified among 1120 HTLV-I‐seronegative adults followed up for 11 years in an area of Japan endemic for HTLV-I. The geometric mean titer of anti‐HTLV-I was 1:453 in the first year after seroconversion; the titer of each subject did not change significantly during 2‐10 years of followup. HTLV-I proviral DNA load was quantified in 15 seroconverters, and a broad range of levels was observed—from !10 to 11000 copies/10 5 peripheral blood mononuclear cells. However, there was no obvious change in HTLV-I proviral DNA load over several years within individual subjects. Therefore, both proviral DNA load and humoral response in adult HTLVI seroconverters were shown to stabilize within a few years after initial infection. In addition, 1 subject tested positive for HTLV-I proviral DNA before antibody seroconversion, which suggests the existence of a window period in community-acquired infection. Human T lymphotropic virus type I (HTLV-I) is a causative agent not only for adult T cell leukemia (ATL) but also for several other diseases, such as HTLV-I‐associated myelopathy/ tropical spastic paraparesis and HTLV-I uveitis [1‐6]. The major natural route of HTLV-I transmission in adults in Japan is thought to be sexual contact between spouses, especially from husband to wife [7, 8]. Newly acquired infection can be monitored by seroconversion of anti‐HTLV-I [9]. However, few reports are available about the early events in the natural history of incident HTLV-I infection in community-based populations. The Miyazaki Cohort Study (MCS) was established in 1984 for the primary purpose of investigating the natural history of HTLV-I infection [10]. Of the »2000 subjects enrolled in the cohort, 523 (26%) of 1974 subjects were positive for anti‐ HTLV-I at baseline. Among the anti‐HTLV-I‐negative subjects, a significant number of anti‐HTLV-I seroconversions

Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

During an outbreak of hepatitis B virus (HBV) infection in a hemodialysis unit, patients were assessed for serological viral markers and vaccination status. HBV infection was identified in 26 patients. Twenty of these were positive for hepatitis B surface antigen (HBsAg), and 6 were negative for HBsAg but positive for IgM antibody to hepatitis B core (anti-HBc) and HBV DNA. The primary source of infection was not clearly identified, although 2 patients were suspected to be the index cases. A multiple logistic regression analysis revealed low anti-HBs titers and vaccination status to be independently associated with the risk of acquiring HBV infection. Both the high prevalence of HBV infection (31%) detected in this unit and the low vaccine response (53%) observed reinforce the importance of universal and preventive measures in controlling HBV infection. The detection of HBV DNA in HBsAg-negative/IgM anti-HBc-positive patients emphasizes the value of anti-HBc testing in the routine screening of HBV in hemodialysis units.

We conducted a case-control study in Athens, Greece, to investigate the role of diet in the etiology of hepatocellular carcinoma (HCC). Subjects were 97 incident cases of HCC and 128 controls with no history of cancer admitted for minor ailments in three major hospitals. Information on diet was collected using a validated food frequency questionnaire, and infection with hepatitis virus B (HBV) or C (HCV) was assessed using third-generation assays. Data were modeled through multiple logistic regression. We found no evidence that vegetable intake may reduce the risk of HCC, as reported in earlier investigations. In a multivariate model, only consumption of milk and dairy products appeared to be inversely related to HCC risk (odds ratio = 0.70, 95% confidence interval = 0.49-1.01), but the association was not statistically significant and is likely to have been generated by the multiple comparisons undertaken overall. Our data do not support an association of specific food groups or particular nutrients with the risk of HCC, whether positive or negative for HBV and/or HCV.

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [≥ 2 packs per day, odds ratio (OR)=2.5].This association was stronger in individuals without chronic infection with either HBV or HCV (≥ 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together. Int. J. Cancer 85:498–502, 2000. © 2000 Wiley-Liss, Inc.