Pacific Health Research Institute

Honolulu, HI, United States

Pacific Health Research Institute

Honolulu, HI, United States
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Andriole G.L.,University of Washington | Crawford E.D.,University of Colorado at Denver | Grubb R.L.,University of Washington | Buys S.S.,University of Utah | And 21 more authors.
Journal of the National Cancer Institute | Year: 2012

Background The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial. Methods A total of 76685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38340 men) and control (usual care, which sometimes included opportunistic screening; 38345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided. ResultsApproximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P interaction =. 81), pretrial PSA testing (P interaction =. 52), and comorbidity (P interaction =. 68). Conclusions After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing. Published by Oxford University Press 2012.2012 © Published by Oxford University Press 2012. © 2012 The Author.


Okihiro M.,University of Hawaii at Manoa | White L.,Pacific Health Research Institute
Ethnicity and Disease | Year: 2012

Background: Rapid growth (RG) in early childhood has been associated with increased risk of obesity. The specific intervals when risk is highest have not been well examined and may help identify modifiable risk factors. Objective: To determine the correlation between RG in consecutive time intervals during the first 2 years of life with obesity at 4-5 years. Methods: This was a retrospective study of children attending the largest community health center in Hawaii. Children, aged 4-5 years, with a pre-kindergarten (PreK) well-child physical examination were included; data were abstracted from medical charts. Analyses: Children were classified as overweight (BMI for age/sex 85-94%) or obese (BMI for age/sex ≥ 95%). Moderate and severe rapid growth was defined as an increase in weight-for-height z-score of .67-1.0 SD and ≥1.0, respectively. Relationship between RG and PreK obesity was assessed using logistic regression analyses. Results: 389 children were included: 66% Hawaiian, 21.6% Samoan and 12.3% Filipino. At the PreK 19.6% were obese, and 20.9% were overweight. Severe RG from 12 to 23 months was strongly associated with PreK obesity (OR 4.36, 95% CI 1.85-10.27). Of children with severe RG from 12-23 months, 48% were obese at PreK compared with 16.7% of children with moderate RG and 19.3% of children without RG. Conclusion: Rapid growth between 12 and 23 months, a key period of nutritional transition in toddlers, was strongly associated with obesity at 4 to 5 years of age in this high-risk population of Pacific Island minority subgroups.


Nan H.,Harvard University | Du M.,Harvard University | De Vivo I.,Harvard University | Manson J.E.,Harvard University | And 8 more authors.
Cancer Research | Year: 2011

Epidemiologic studies have linked shortened telomeres with the development of many cancers. However, recent studies have suggested that longer telomeres may lead to prolonged senescence in melanocytes, providing increased opportunity for malignant transformation. We therefore examined whether shorter prediagnostically measured relative telomere length in peripheral blood leukocytes (PBL) was associated with a decreased risk of cutaneous melanoma. Telomere length in prospectively collected PBLs was measured in incident melanoma cases and age-matched controls selected from participants in three large prospective cohorts: the Women's Health Initiative Observational Study (WHI-OS), the Health Professionals Follow-up Study (HPFS), and the Nurses' Health Study (NHS). Shorter telomere lengths were associated with decreased risk of melanoma in each cohort. The P trend across quartiles was 0.03 in the WHI-OS and 0.008 in the HPFS. When combining these two datasets with published data in the NHS(P trend, 0.09), compared with individuals in the fourth quartile (the longest telomere lengths), those in the first quartile had an OR of 0.43 (95% CI: 0.28-0.68; P trend, 0.0003). Unlike findings for other tumors, shorter telomeres were significantly associated with a decreased risk of melanoma in this study, suggesting a unique role of telomeres in melanoma development. ©2011 AACR.


Wang H.,University of Hawaii at Manoa | Yamamoto J.F.,University of Hawaii at Manoa | Caberto C.,University of Hawaii at Manoa | Saltzman B.,University of Hawaii at Manoa | And 6 more authors.
Carcinogenesis | Year: 2011

Animal work implicates chemical carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to the development of colorectal cancer (CRC). The epidemiologic evidence, however, remains inconsistent possibly due to intra-individual variation in bioactivation of these compounds. We conducted a case-control study of colorectal adenoma (914 cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans, European Americans and Native Hawaiians to investigate the association of genetic variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR and ARNT) identified through sequencing with risk of colorectal neoplasia, as well as their interactions with smoking and intakes of red meat and HAAs. The A allele for ARNT rs12410394 was significantly inversely associated with CRC [odds ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes: 1.00, 0.66 (0.48-0.89), 0.54 (0.37-0.78), Ptrend = 0.0008] after multiple comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated with CRC, where each copy of the T allele was associated with reduced risk (OR: 0.72, 95% CI: 0.58-0.88, Ptrend = 0.0017). No heterogeneity of genetic effects across racial/ethnic groups was detected. In addition, no significant interaction was observed after adjusting for multiple testing between genetic variants and packyears of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC. © The Author 2010. Published by Oxford University Press. All rights reserved.


Sonnen J.A.,University of Washington | Santa Cruz K.,University of Minnesota | Hemmy L.S.,University of Minnesota | Woltjer R.,Oregon Health And Science University | And 9 more authors.
Archives of Neurology | Year: 2011

Background: Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. Objective: To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Design: Autopsy study. Setting: Community- and population based. Participants: A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Main Outcome Measures: Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Results: Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these,6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. Conclusions: These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts. ©2011 American Medical Association. All rights reserved.


Schoen R.E.,University of Pittsburgh | Pinsky P.F.,U.S. National Cancer Institute | Weissfeld J.L.,University of Pittsburgh | Yokochi L.A.,Pacific Health Research Institute | And 8 more authors.
Gastroenterology | Year: 2010

Background & Aims: The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis. Methods: We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. Results: Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with ≥3 NAAs (n = 117), 46.7% in those with 1-2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received ≥2 surveillance examinations versus 26.9% for those with ≥3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. Conclusions: In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed. © 2010 AGA Institute.


Masuda E.M.,University of Hawaii at Manoa | Kistner R.L.,Kistner Vein Clinic | Musikasinthorn C.,University of Hawaii at Manoa | Liquido F.,University of Hawaii at Manoa | And 2 more authors.
Journal of Vascular Surgery | Year: 2012

Background: Controversy persists as to whether all calf vein thrombi should be treated with anticoagulation or observed with duplex surveillance. We performed a systematic review of the literature to assess whether data could support either approach, followed by examination of its natural history by stratifying results according to early clot propagation, pulmonary emboli (PE), recurrence, and postthrombotic syndrome (PTS). Methods: A total of 1513 articles were reviewed that were published from January 1975 to August 2010 using computerized database searches of PubMed, Cochrane Controlled Trials Register, and extensive cross-references. English-language studies specifically examining calf deep vein thrombosis (C-DVT) defined as axial and/or muscular veins of the calf, not involving the popliteal vein, were included. Papers were independently reviewed by two investigators (E.M., F.L.) and quality graded based on nine methodologic standards reporting on four outcome parameters. Results: Of the 1513 citations reviewed, 31 relevant papers meeting predefined criteria were found: six randomized controlled trials (RCT) and 25 observational cohort studies or case series. There was a single RCT directly comparing anticoagulation with no anticoagulation with compression and duplex surveillance, and they found no difference in propagation, PE, or bleeding in a low-risk population. Based on two studies of moderately strong methodology, C-DVT propagation was reduced with anticoagulation. When treatment was unassigned, moderately strong evidence suggested that about 15% propagate to the popliteal vein or higher. However, based on nonrandomized data but with moderate to high quality (level A and B studies), propagation to popliteal or higher was 8% in those with no anticoagulation treated with surveillance only. Propagation involving adjacent calf veins but remaining in the calf occured in up to one-half of all those who propagate. Major bleeding was an intended endpoint in three RCTs and was reported as 0% to 6%, with a trend toward lower bleeding risk in more recent studies. PE during surveillance in studies with unassigned treatment was strikingly lower than the historical reports of PE recorded at presentation, emphasizing the distinction that must be made between the two entities. Recurrence in C-DVT is lower than thigh DVT, and data suggest that in low-risk groups with transient risk factors, 6 weeks of anticoagulation may be sufficient, as opposed to 12 weeks. Studies of PTS reported that patients with C-DVT had fewer symptoms than their thigh DVT counterparts. Approximately one out of 10 showed symptoms of CEAP Class 4 to 6; however, C5 or C6 with healed or active ulceration were not commonly encountered. Conclusions: No study of strong methodology could be found to resolve the controversy of optimal treatment of C-DVT. Given the risks of propagation, PE, and recurrence, the option of doing nothing should be considered unacceptable. In the absence of strong evidence to support anticoagulation over imaging surveillance with selective anticoagulation, either method of managing calf DVT must remain as current acceptable standards. Copyright © 2012 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.


Wadwa R.P.,Aurora University | Urbina E.M.,University of Cincinnati | Anderson A.M.,Wake forest University | Hamman R.F.,University of Colorado at Denver | And 4 more authors.
Diabetes Care | Year: 2010

OBJECTIVE- Arterial stiffness occurs early in the atherosclerotic process; however, few data are available concerning risk factors for arterial stiffness in youth with diabetes. We identified factors associated with arterial stiffness in youth with diabetes and assessed the effects of these factors on the relationship between arterial stiffness and diabetes type (type 1 vs. type 2). RESEARCH DESIGN AND METHODS- A subset of patients from the SEARCH for Diabetes in Youth study with type 1 (n = 535) and type 2 diabetes (n = 60), aged 10-23 years (52% male; 82% non-Hispanic white; diabetes duration 65 ± 49 months) had arterial stiffness, anthropometrics, blood pressure, fasting lipids, and A1C measured. Arterial stiffness was measured by brachial distensibility (brachD), pulse wave velocity (PWV), and augmentation index adjusted to heart rate of 75 beats/min (AI75). RESULTS- Youth with type 2 diabetes had worse brachD (5.2 ± 0.9 vs. 6.1 ± 1.2%/ mmHg), PWV (6.4 ± 1.3 vs. 5.3 ± 0.8 m/s), and AI75 (6.4 ± 9.9 vs. 2.2 ± 10.2%) than those with type 1 diabetes (P < 0.01 for each). These differences were largely mediated through increased central adiposity and higher blood pressure in youth with type 2 diabetes. We also found a pattern of association of arterial stiffness measures with waist circumference and blood pressure, independent of diabetes type. CONCLUSIONS- Youth with type 2 diabetes have worse arterial stiffness than similar youth with type 1 diabetes. Increased central adiposity and blood pressure are associated with measures of arterial stiffness, independent of diabetes type. Whether these findings indicate that youth with type 2 diabetes will be at higher risk for future complications requires longitudinal studies. © 2010 by the American Diabetes Association.


Le Marchand L.,University of Hawaii at Manoa | Wang H.,University of Hawaii at Manoa | Selhub J.,Tufts University | Vogt T.M.,Kaiser Permanente | And 2 more authors.
Cancer Causes and Control | Year: 2011

Circulating level of vitamin B6 has been inversely associated with colorectal cancer (CRC) risk but, unlike for folate, few studies have examined the relationship of vitamin B6 to colorectal adenoma, the precursor lesion to most CRCs. We measured plasma levels of folate, vitamin B6, and vitamin B12 in 241 patients with pathologically confirmed first occurrence of colorectal adenoma and 280 controls among Caucasians, Japanese Americans, and Native Hawaiians undergoing flexible sigmoidoscopy screening in Hawaii. High plasma level of vitamin B6 was independently inversely associated with risk of colorectal adenoma [multivariate odds ratios (95% confidence intervals): 1.0, 0.71 (0.45-1.13) and 0.44 (0.26-0.74) from the lowest to the highest tertile, respectively, p trend = 0.002]. Plasma folate was not associated with adenoma after adjustment for plasma vitamin B6 (p trend > 0.3). No association was observed with plasma vitamin B12. No significant interaction was detected between the three B vitamins and alcohol intake, multivitamin use or MTHFR C677T. The results provide evidence for an inverse association of plasma vitamin B6 levels with risk of colorectal adenoma. This study expands previous findings and suggests that vitamin B6 may be protective against the early stages of colorectal carcinogenesis. © 2011 Springer Science+Business Media B.V.


Morland L.A.,National Center for Pacific Islands Division | Greene C.J.,National Center for Pacific Islands Division | Greene C.J.,National Center for Dissemination and Training Division | Rosen C.S.,National Center for Dissemination and Training Division | And 6 more authors.
Journal of Clinical Psychiatry | Year: 2010

Objective: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD). Method: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n = 64) or via videoteleconferencing (n = 61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment. The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008. Results: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63. Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("noninferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy. Participants in the in-person condition reported significantly higher group therapy alliance. Conclusions: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations. Trial Registration: clinicaltrials.gov Identifier: NCT00122109. © Copyright 2010 Physicians Postgraduate Press, Inc.

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