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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.

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.

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.

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

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.

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.

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.

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

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.

Purpose of the Study: Older adults who are depressed or are caregivers experience more sleep problems, whereas recent studies suggest that adults with high positive affect (PA) have fewer sleep problems. This study examined whether the associations of PA and depressive symptoms with sleep problems differed between caregivers and noncaregivers. Design and Methods: Face-to-face interviews were conducted with 92 caregivers to a relative or friend with Alzheimer’s disease or Parkinson’s disease, and 137 noncaregivers aged 60 years and older (mean 73.8±7.9 years) from the Boston, Massachusetts, metropolitan area. Sleep problems were assessed using the Pittsburgh Sleep Quality Index (PSQI). Respondents were categorized as high PA (n = 122), low PA (n = 69), and depressive symptoms (n = 38) based on the Center for Epidemiologic Studies-Depression scale. Results: The mean PSQI score was 5.19 (SD = 3.26) and did not differ by caregiving status. In multivariable linear regression analyses among caregivers, those with high PA had significantly fewer sleep problems than their counterparts with low PA (adjusted mean PSQI score was 4.16 [SE = 0.50] vs. 5.69 [SE = 0.58], p = .05), whereas caregivers with depressive symptoms reported slightly more problems (adjusted mean 6.92 [SE = 0.80], p = .22). High PA and depressive symptoms were not associated with sleep problems among noncaregivers (adjusted mean PSQI scores were 4.88 [SE = 0.35], 5.38 [SE = 0.51], and 5.99 [SE = 0.73], respectively). Similar associations were found with PSQI scale components. Implications: Results suggest that routine screening and interventions to increase PA may reduce sleep problems among older caregivers.

We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who has breastfed for > or = 24 months had an odds ratio of 0.50 (95% confidence interval 0.23-1.41). A reduction of the odds ration was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is a marginal importance.

The purpose of the Miyazaki Cohort Study is to describe and analyze the natural history of human T-cell lymphotropic virus type I (HTLV-I) in a highly endemic population in southwestern Japan. As of August 1995, 1,960 individuals have been enrolled, of whom 27% were HTLV-I antibody positive at baseline. Our achievements over the past decade of following this cohort include the identification of several viral markers that characterize high-risk carriers and the documentation that carriers have subclinical evidence of impaired cellular immunity. We have begun to estimate the impact of the infection on the health of carriers and have found that men are at greater risk of HTLV-I-associated diseases than women. We have been able to identify prospectively risk factors associated with sexual transmission. Most important, by identifying subclinical markers of pathogenesis, we hope to provide the foundation for developing interventions to prevent HTLV-I-associated disease.

In a hospital-based case-control study in Athens, we examined the association between the use of oral contraceptives and menopausal estrogens and the risk of breast cancer. Eight hundred and twenty patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to the cases by age and interviewer. The data were modeled through logistic regression, controlling for demographic and reproductive variables. Odds ratio patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not elevated among ever-users of oral contraceptives, regardless of age at diagnosis of breast cancer, duration of oral contraceptive use or timing of use in relation to first full-term pregnancy. Among peri- and post-menopausal women who ever used menopausal estrogens, with never-users as the baseline, a statistically significant elevated odds ratio was found after adjusting for age at menopause. © 1995 Wiley-Liss, Inc.

Background Experimental animal studies suggest that olive oil consumption, as contrasted to consumption of other fat types, does not enhance the occurrence of chemically induced mammary tumors, but human data are sparse. Furthermore, evidence is inconclusive concerning the role of food groups, as distinct from that of major nutrients, in the etiology of breast cancer in women. Purpose This analysis was conducted to evaluate and quantify the effect of consumption of olive oil, margarine, and a range of food groups on the risk of breast cancer. Methods Data from a comprehensive, semiquantitative food-frequency questionnaire administered to 820 women with breast cancer and 1548 control women from the study base were used to calculate odds ratios (ORs) and X statistics of linear trend for the consumption of olive oil, margarine, and a series of food groups classified in quintiles. Adjustment for the effects of reproductive risk factors, energy intake, and mutual confounding influences was implemented through unconditional logistic regression modeling. Results Vegetable consumption and fruit consumption were independently associated with statistically significant reductions of breast cancer risk by 12% and 8%, respectively, per quintile increase; no significant associations were evident for the other food groups examined. Increased olive oil consumption was associated with significantly reduced breast cancer risk (OR = 0.75 [95% confidence interval = 0.57-0.98] for more than once a day versus once a day), whereas increased margarine consumption was associated with significantly increased risk (OR = 1.05 [95% confidence interval = 1.00-1.10] for an increment of four times a month). The olive oil association was apparently concentrated among postmenopausal women, but the relevant interaction term was not statistically significant; there was no suggestion of interaction with menopausal status for consumption of either vegetables, fruits, or margarine. Conclusions Although major categories of macronutrients do not show significant associations with breast cancer risk in most studies, including the present one, vegetables and fruits are inversely, significantly, and strongly associated with this risk. There also is evidence that olive oil consumption may reduce the risk of breast cancer, whereas margarine intake appears to be associated with an elevated risk for the disease.

Purpose: There is no consensus in the oncology community about the optimal model for anticoagulation management of ambulatory cancer patients. To understand oncologists’ preferences regarding anticoagulation management, we compared the characteristics of patients referred to an oncology-oriented anticoagulation management service with “usual care” patients managed by the patient’s primary oncologist. Methods: We performed a retrospective medical record review of ambulatory oncology patients’ anticoagulation care at a comprehensive cancer center. We examined the characteristics of 33 patients anticoagulated before implementation of a dedicated oncology anticoagulation management service. We compared this group with 33 patients managed by the anticoagulation management service and with 39 usual care patients managed by the primary oncologist after the anticoagulation management service was created. We also examined differences in laboratory test utilization, time in the therapeutic range (for patients anticoagulated with warfarin), and anticoagulation-related adverse events during a 3-month assessment period. Results: Anticoagulation management service patients were more likely to be treated for hematologic malignancies, use erythropoietin stimulating agents, and require warfarin management for previous venous thromboembolic disease compared to usual care patients. In contrast, oncologists were more likely to manage anticoagulation care of patients with advanced solid tumors undergoing active chemotherapy. Anticoagulation management service and usual care patients on warfarin therapy had comparable time in the therapeutic range and complication rates. Conclusion: Oncologists selectively referred patients to the anticoagulation management service. Anticoagulation management service patients’ warfarin control and complication rates were comparable to care provided by the primary oncologist, suggesting that an oncology-specific anticoagulation management service may be a feasible and effective option for anticoagulation management of ambulatory oncology patients.

Theories of stress-induced metabolic syndrome predict that job strain would increase risk. Few studies have evaluated this association.To evaluate the association between job strain and the risk of metabolic syndrome.We investigated associations between job strain and incident metabolic syndrome adjusted for sociodemographic factors, health behaviors, and depressive symptoms over 5 years among 2966 black and white men and women in the Coronary Artery Risk Development in Young Adults study. Job strain was categorized by Karasek's model: high demands/low control; high demands/high control; low demands/low control; and low demands/high control.Compared with persons in low-strain jobs, men in active jobs (adjusted hazards ratio, 2.7; 95% confidence interval, 1.5 to 4.9) and women in high strain jobs (adjusted hazards ratio, 2.2; 95% confidence interval, 1.0 to 4.6) had significantly increased risk of metabolic syndrome.Job strain may be a modifiable risk factor for metabolic syndrome and subsequent cardiovascular disease.

Objectives. We investigated potential risk factors for active injection drug use (IDU) in an inner-city cohort of patients infected with hepatitis C virus (HCV). Methods. We used log-binomial regression to identify factors independently associated with active IDU during the first 3 years of follow-up for the 289 participants who reported ever having injected drugs at baseline. Results. Overall, 142 (49.1%) of the 289 participants reported active IDU at some point during the follow-up period. In a multivariate model, being unemployed (prevalence ratio [PR] = 1.93; 95% confidence interval [CI] = 1.24, 3.03) and hazardous alcohol drinking (PR = 1.67; 95% CI = 1.34, 2.08) were associated with active IDU. Smoking was associated with IDU but this association was not statistically significant. Patients with all 3 of those factors were 3 times as likely to report IDU during follow-up as those with 0 or 1 factor (PR = 3.3; 95% CI = 2.2, 4.9). Neither HIV coinfection nor history of psychiatric disease was independently associated with active IDU. Conclusions. Optimal treatment of persons with HCV infection will require attention to unemployment, alcohol use, and smoking in conjunction with IDU treatment and prevention.

The Greek diet is characterized by a high total fat but low saturated fat intake. In a hospital-based case-control study of female breast cancer conducted in Athens (1989-91), 820 patients with confirmed cancer of the breast were compared with 795 orthopaedic patient controls and 753 hospital visitor controls, matched to the cases by age and interviewer. Diet was ascertained through a semiquantitative food frequency questionnaire; macronutrient intakes were estimated from the nutrient content of a selected typical portion size for each specified food item, summed for all items. Logistic regression was used to analyse the data, controlling for demographic and reproductive risk factors for breast cancer as well as for total energy intake and mutual confounding influences among nutrients. There was no significant or suggestive association of total protein, total fat, categories of fat or total carbohydrates with breast cancer risk. Thus, the mutually adjusted relative risk per quintile and (in parenthesis) 95% confidence interval were: for protein, 1.06 (0.94-1.20); saturated fat, 0.99 (0.89-1.11); monounsaturated fat, 0.97 (0.88-1.07), polyunsaturated fat, 1.05 (0.97-1.13); and total carbohydrates, 1.03 (0.94-1.12). In alternative analytical approaches only total protein appeared to be positively associated to the occurrence of breast cancer with some consistency, but the results were far from statistically significant. These findings do not support a role for fat or other energy-generating nutrients in the aetiology of breast cancer.

We have examined the association of alcohol intake during various life periods, by beverage category, with breast cancer risk in Greece. A hospital-based case-control study was performed in Athens, involving 820 women with breast cancer as well as 795 orthopedic patients and 753 healthy visitor controls. Relative risk patterns were very similar with either control series, which were therefore combined to increase precision of the estimates. Drinkers of beer were at significantly elevated risk for breast cancer [odds ratio (OR), 1.34 (95% confidence interval, 1.05-1.71)]. However, drinkers of other alcoholic beverages were not at increased risk. Among beer drinkers there was no dose-response, and drinkers of both beer and other beverages had a lower OR compared to drinkers of beer only. By contrast, drinkers of 3 or more glasses of alcohol per day, mostly of spirits, were at elevated risk for breast cancer [OR for 3 - < 4 glasses per day, 3.01 (1.14-7.95); OR for 4 or more glasses per day, 3.79 (1.05-13.71)]. Reported frequency of consumption was a stronger predictor of breast cancer risk than either duration-weighted total consumption or consumption before the age of 30 years. There were no coherent patterns for interaction with menopausal status, obesity or use of menopausal estrogens. The association of very low levels of alcohol intake with breast cancer risk may be due to confounding, whereas drinking 3 or more glasses of alcoholic beverages daily appears to genuinely increase breast cancer risk, perhaps by acting as a late-stage growth enhancing factor. However, the data also are compatible with a linear relationship that has no threshold.

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.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.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.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.

Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied. The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% (95% confidence interval (CI): 0.8 - 1.3%) and 0.1% (95% CI: 0.1 - 0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91 -fold increased risk of HCC (95% CI: 28.99 - 136.52), a 29.97 -fold increased risk of NHL during the first year of follow-up (95% CI: 6.08 - 147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36 - 4.41). Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67 - 13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.

Item does not contain fulltext BACKGROUND: Evidence suggests that patients can report a variety of adverse events (AEs) not captured by traditional methods such as a chart review. Little is known, however, about whether patient reports are useful for measuring patient safety. OBJECTIVES: To examine the degree to which physician reviewers agreed that patient reports of "negative effects" constituted AEs, and to identify questionnaire items that affected reviewers' judgments. METHODS: We surveyed patients discharged from Massachusetts hospitals in 2003 to elicit information about negative effects associated with hospitalization. Physician reviewers judged whether patient-reported negative effects represented AEs, and classified the severity of the event. Likelihood ratios were calculated to assess whether patient responses to questionnaire items affected reviewers' judgments. RESULTS: Of the 2582 patients surveyed, 753 patients reported 1170 negative effects, and 71.2% of these effects were classified as AEs by physician reviewers. Negative effects most likely to be classified as AEs involved newly prescribed medications and changes to previously prescribed medications. Additional information elicited from follow-up survey questions modestly affected reviewers' classification of serious AEs. Negative effects reported by women, younger patients, those reporting better health status, and those not admitted through the emergency department were more likely to be classified as AEs. CONCLUSIONS: Many patients were able to identify care-related AEs. Patient responses to questions about the sequelae of the events provided limited additional information for physicians to use in gauging the presence and severity of the event. Patient reports complement other incident-detection methods by providing information that is credible and unavailable from other sources. 01 oktober 2011

Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality.We assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child-Pugh-Turcotte (CPT) and model of end-stage liver disease (MELD) scores.A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86-0.96), CPT 0.91 (0.79-0.96), APRI 0.88 (0.80-0.93), Fib-4 0.87 (0.77-0.92), MELD 0.84 (71-0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT.Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD.

Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV.Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 x 10(-7) and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-gamma-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment.The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.

A nested case-control study was conducted to examine the association between host immune status, as characterized by serum immune marker levels, and the development of hepatocellular carcinoma (HCC) up to 8 years later in persons with chronic hepatitis C virus (HCV) infection. Cases (n = 39) and matched controls (n = 117) were selected from participants of the Town C HCV Study in Japan between 1996 and 2004 and matched on age at first available sample (±1 year), gender, and length of follow-up. Separate analyses were done for each of three serum immune markers: soluble tumor necrosis factor-receptor II (sTNF-R2) and soluble intercellular adhesion molecule-1 (sICAM-1), as indicators of type 1, cell-mediated immune response, and soluble CD30 (sCD30), as an indicator of type 2, humoral immune response. The median concentrations of sTNF-R2, sICAM-1, and sCD30 among controls were 3,170 pg/mL, 305 ng/mL, and 3.0 units/mL, respectively, and were higher among cases (3,870 pg/mL, 372 ng/mL, and 3.3 units/mL, respectively). The risk of developing HCC among subjects with immune marker concentrations above the median levels of the controls was >2-fold greater than among subjects with lower concentrations for all three markers [sTNF-R2: odds ratio (OR), 6.9; 95% confidence interval (95% CI), 2.4-20.5; sICAM-1: OR, 2.0; 95% CI, 0.9-4.1; and sCD30: OR, 2.1; 95% CI, 1.0-4.7]. Simultaneous adjustment for all three markers revealed only sTNF-R2 to be associated with HCC risk (OR, 6.4; 95% CI, 2.0-20.6). Adjustment for alcohol consumption and HCV serotype did not materially alter these associations. Results from this prospective, community-based study suggest that a dysregulation in both type 1–related and type 2–related host immunity contributes to the development of HCV-associated HCC. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2521–5)

The clinical features of hepatitis C virus (HCV) carriers with persistently normal alanine aminotransferase (PNALT) levels (ALTor = 34 IU/l) have not been fully elucidated. We investigated clinical factors associated with ALT flare-up in PNALT individuals in a HCV hyperendemic area of Japan.We analyzed 101 HCV carriers who had PNALT between 1993 and 2000. The first occurrence of ALT flare-up (ALTor = 35 IU/l) between 2001 and 2005 was evaluated by the Kaplan-Meier method. Multivariate analysis of factors predicting ALT flare-up were conducted using Cox proportional hazards models.The mean follow-up period was 2.8 years, and the 5-year cumulative incidence of ALT flare-up was estimated to be 31.8%. In multivariate analysis, an ALT level of 20-34 IU/l and a high serum ferritin level (or =90 ng/ml) in the most recently available data up to the year 2000, as well as H63D heterozygosity in the HFE gene, were independently and strongly associated with the incidence of ALT flare-up (Hazard ratios = 5.6, 3.1, and 4.8, respectively). In addition, HFE H63D heterozygosity was significantly associated with higher serum ferritin levels in subjects with PNALT (153.8 + or - 73.3 ng/ml in subjects with the 63HD genotype vs. 89.4 + or - 51.3 ng/ml in subjects with the 63HH genotype, P = 0.043).HCV carriers with PNALT in this population were at risk for ALT flare-up. Basal ALT levels, serum ferritin levels, and HFE polymorphism are potentially important predictors of ALT flare-up.

Background The clonal expansion of human T lymphotropic virus type 1 (HTLV-1)-infected T cells is considered to be important for the maintenance of infection. However, the process by which the clonality of HTLV-1-infected T cells is established is not understood. Methods HTLV-1 clonality in 4 adult seroconverters was analyzed by inverse long polymerase chain reaction (PCR) followed by cloning of the PCR products and evaluation of restriction fragment-length polymorphism. The results were compared with those for 8 long-term HTLV-1 carriers. Results The clonality of HTLV-1-infected T cells in the seroconverters arose stochastically and was variable 3-5 years after seroconversion. On the basis of the frequency with which clones of cells infected with unique HTLV-1 provirus integration sites appeared, it was clear that the seroconverters had a greater number of unique clones with fewer infected cells than did the long-term carriers. Conclusions The clonality of the HTLV-1-infected T cells in the adult seroconverters, who had been newly infected via HTLV-1-carrier spouses, was more heterogeneous and less stable than that of the HTLV-1-infected T cells in long-term carriers, who were more likely to have been infected during infancy. The mechanism for the selective maintenance of certain clones in asymptomatic HTLV-1 carriers likely plays a role in the initiation of leukemogenesis.

Human T lymphotropic virus type I (HTLV-I) is endemic in southern Japan and the Caribbean, but the incidence of HTLV-I-associated diseases varies across geographic areas. We compared markers of disease pathogenesis among 51 age- and sex-matched HTLV-I carrier pairs from Japan and Jamaica. The mean antibody titer (P = .03) and detection of anti-Tax antibody (P = .002) were higher in Jamaican subjects than in Japanese subjects, but provirus load was similar between the 2 groups (P = .26). The correlation between antibody titer and provirus load was more prominent among Jamaican subjects than among Japanese subjects (P = .06). These findings underscore the differences in host immune response to HTLV-I infection in 2 populations.

Early age at menarche and tallness are associated with increased risk for breast cancer, and emerging evidence suggests that body size at birth also is positively associated with breast cancer risk in adulthood. We have explored whether this effect of birth size could be mediated by influencing age at menarche or body height during adolescence. Information on age at menarche and adolescent height among 3,343 Norwegian girls 13 to 19 years of age, born at term and whose mothers had no history of gestational disease was individually linked to information on birth weight and length recorded in the national Medical Birth Registry. We related quintiles of birth size, adjusted for length of gestation, to age at menarche and adolescent height and weight, using general linear modeling and Cox regression analyses. In a subsample of the population, we also had information on maternal age at menarche, as well as adult height and body mass index in both parents. We explored whether parental factors confounded the association between perinatal predictors and adolescent outcomes in the daughters. We found that age at menarche tended to occur earlier with decreasing birth weight (p for trend = 0.03), and girls who were thin at birth (i.e., in the lowest quintile of ponderal index) had an earlier age at menarche than other girls (p = 0.02). Weight and length at birth were strongly and positively related to tallness during adolescence (p for trend < 0.001), but ponderal index, indicating obesity at birth, was negatively associated with adolescent height (p for trend = 0.002). Adjustment for parental height, body mass index and maternal age at menarche, in the subsample where this information was available, indicated no substantial confounding by these parental factors. Our results suggest that a positive association between birth size and adult breast cancer is not likely to be mediated by early age at menarche, but possibly by increased body height in adolescence.

Background Despite international efforts to prevent hepatitis B virus (HBV) infection through global vaccination programs, new cases are still being reported throughout the world. Methods To supply data that might assist in improving preventive measures and national surveillance for HBV infection, a cross-sectional study was conducted among individuals referred to the Brazilian National Reference Center for Viral Hepatitis (Rio de Janeiro) during a two-year period. Reported risk factors among infected subjects ("HBV-positive") were compared to those of subjects never exposed ("HBV-negative") to HBV. Two subgroups were further identified within the HBV-positive group, "acute" infection and "non-acute" infection. Results A total of 1,539 subjects were tested for HBV, of which 616 were HBV-positive (79 acute infection and 537 non-acute infection). HBV-positive subjects were more likely to be of male gender (63% versus 47%); and to report multiple sexual partners (12% versus 6%) and illicit drug use (IDU and/or intranasal cocaine use) (6% versus 3%). Among the HBV-positive subgroups, age differed significantly, with 48% being under 30 years of age in subjects acutely infected compared to 17% in those with non-acute infection. Conclusions The association of multiple sexual partners with past HBV infection and the age distribution of currently infected subjects suggest that sexual transmission played a major role in the transmission of HBV in this study population. Thus, vaccination during adolescence should be considered.

Hepatitis C virus (HCV) is an important cause of liver disease throughout the world. However, the natural history and pathogenesis of this infection is still not completely understood. The aim of this study was to characterize the evolution of incident, asymptomatic HCV infection in a community-based population in Japan. The Miyazaki Cohort Study is a prospective study of adult residents in two villages, one of which has a very high prevalence of HCV. Nine hundred and seventy-three people from this village were enrolled in the cohort between 1984 and 1995, with antibodies to HCV (anti-HCV) found in 23%. During subsequent visits to annual health screens, new HCV seroconverters were identified among susceptible individuals, and their sequential samples were tested for anti-HCV, HCV-RNA, and HCV core antigen. Fourteen participants (six males, eight females) acquired anti-HCV during the first 11 years of study follow-up, at an incidence rate of 362 per 100 000 person-years. Detectable HCV-RNA and high anti-HCV titres (> 1:2048) were observed for more than 5 years following seroconversion in 80% (8/10) of seroconverters with sufficient information, indicating the development of persistent infection in these subjects. Three (37.5%) of the eight sero converters with persistent infection had fairly consistent, albeit mild, alanine aminotransferase elevations (30-130 IU/L) during the study. Anti-HCV seroconversions occurred at a very high rate in this community-based population in Japan, in which this infection is endemic. Persistence also developed at a high frequency among the cases of newly acquired infection, although the associated liver enzyme abnormalities were mild.