Search

There is a strong familial predisposition to type 2 diabetes, hypertension, and cardiovascular disease. The authors evaluated the association between a family history of these diseases and a large panel of cardiovascular risk factors in 1,431 Mexican American subjects who were enrolled in the San Antonio Family Heart Study in San Antonio, Texas. The baseline phase of the study covered 1992-1996. Diabetes and hypertension were diagnosed according to standard clinical criteria, while cardiovascular disease was defined as a history of heart attack or heart surgery. The prevalence of diabetes, hypertension, and cardiovascular disease in this population was 15%, 12%, and 3%, respectively. For each unaffected subject, the authors computed a family history score based on the presence or absence of disease in parents and older siblings, and correlations between cardiovascular risk factors and family history scores were estimated by using likelihood-based variance component methods. Diabetes family history score was significantly correlated with a broad panel of cardiovascular risk factors, including glucose and insulin, obesity, blood pressure, triglycerides, and total cholesterol. Hypertension family history score was significantly correlated with glucose, blood pressure, body mass index, waist circumference, total cholesterol, and triglycerides. These results support the idea that genes that confer a risk for diabetes, and to a lesser extent hypertension, adversely alter the cardiovascular risk profile long before the manifestation of clinical disease.

The increased occurrence of type 2 diabetes and its clinical correlates is a global public health issue, and there are continued efforts to find its genetic determinant across ethnically diverse populations. The aims of this study were to determine the heritability of diabetes and metabolic syndrome phenotypes in the Arizona Insulin Resistance (AIR) registry and to perform an association analysis of common single nucleotide polymorphisms (SNPs) identified by GWAS with these traits. All study participants were Mexican Americans from the AIR registry.Metabolic, anthropometric, demographic and medical history information was obtained on the 667 individuals enrolled in the registry.The heritability estimates were moderate to high in magnitude and significant, indicating that the AIR registry is well suited for the identification of genetic factors contributing to diabetes and the metabolic syndrome. From the 30 GWAS genes selected (some genes were represented by multiple SNPs), 20 SNPs exhibited associations with one or more of the diabetes related traits with nominal significance (p ≤ 0.05). In addition, 25 SNPs were nominally significantly associated with one or more of the metabolic phenotypes tested (p ≤ 0.05). Most notably, 5 SNPs from 5 genes [body mass index (BMI), hip circumference: rs3751812/FTO; fasting plasma glucose, hemoglobin A1c: rs4607517/GCK; very-low-density lipoprotein: rs10830963/MTNR1B; BMI: rs13266634/SLC30A8, and total cholesterol, low-density lipoprotein: rs7578597/THADA] were significantly associated with obesity, glycemic, and lipid phenotypes when using the multiple testing significance threshold of 0.0015.These findings extend previous work on Mexican Americans to suggest that metabolic disease is strongly influenced by genetic background in this high-risk population.

Background/Aims Adherence to certain effective and widely prescribed cardiovascular (CVD) medications is poor. The purpose of this analysis is to demonstrate the effective implementation of a cost-effective and easily disseminable population-level HIT adherence intervention.

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening.Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization.A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening.receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression.Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening.More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

This paper reports on and discusses the findings of an online survey initiated by the Donor Sibling Registry of 108 parents of children conceived following oocyte donation. Respondents generally supported early disclosure of donor conception to the child, although some bias in favour of disclosure cannot be excluded, given the recruitment source. Even so, extensive uncertainty regarding the optimum time for disclosure was evident. Around half of the parents who had either expressly chosen (50.0%), or had been given no choice of, an anonymous donor (54.1%) subsequently wished they had used an open-identity donor. A total of 87% of respondents showed interest in identifying and making contact with their donor and with other families containing children sharing the same donor, and 19% had already made such contact. The survey revealed considerable variations in respondents’ experiences of clinic practices regarding the availability of counselling, information provided about choice of donor type, advice regarding disclosure and the reporting of births, indicating keys areas for improved professional practice.\ud \ud This paper reports on and discusses the findings of an online survey initiated by the Donor Sibling Registry of 108 parents of children conceived following ooctye donation. Respondents generally supported early disclosure of donor conception to the child, although extensive uncertainty regarding the optimum time for disclosure was evident. Around half of the parents who had either expressly chosen, or had been given no choice of, an anonymous donor subsequently wished they had used an open identity donor. A number of respondents showed interest in identifying and making contact with their donor and with other families containing children sharing the same donor, and a minority had already made such contact. The survey revealed considerable variations in respondents’ experiences of clinic practices regarding the availability of counselling, information provided about choice of donor type, advice regarding disclosure and the reporting of births, indicating keys areas for improved professional practice.

Electronic decision-support systems appear to enhance care, but improving both tools and work practices may optimize outcomes. Using qualitative methods, the authors' aim was to evaluate perspectives about using the Patient Panel-Support Tool (PST) to better understand health care workers' attitudes toward, and adoption and use of, a decision-support tool. In-depth interviews were conducted to elicit participant perspectives about the PST-an electronic tool implemented in 2006 at Kaiser Permanente Northwest. The PST identifies "care gaps" and recommendations in screening, medication use, risk-factor control, and immunizations for primary care panel patients. Primary care physician (PCP) teams were already grouped (based on performance pre- and post-PST introduction) into lower, improving, and higher percent-of-care-needs met. Participants were PCPs (n=21), medical assistants (n=11), and quality and other health care managers (n=20); total n=52. Results revealed that the most commonly cited benefit of the PST was increased in-depth knowledge of patient panels, and empowerment of staff to do quality improvement. Barriers to PST use included insufficient time, competing demands, suboptimal staffing, tool navigation, documentation, and data issues. Facilitators were strong team staff roles, leadership/training for tool implementation, and dedicated time for tool use. Higher performing PCPs and their assistants more often described a detailed team approach to using the PST. In conclusion, PCP teams and managers provided important perspectives that could help optimize use of panel-support tools to improve future outcomes. Improvements are needed in tool function and navigation; training; staff accountability and role clarification; and panel management time.

To estimate the cost-effectiveness of an automated telephone intervention for colorectal cancer screening from a managed care perspective, using data from a pragmatic randomized controlled trial.Intervention patients received calls for fecal occult blood testing (FOBT) screening. We searched patients' electronic medical records for any screening (defined as FOBT, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy) during follow-up. Intervention costs included project implementation and management, telephone calls, patient identification, and tracking. Screening costs included FOBT (kits, mailing, and processing) and any completed screening tests during follow-up. We estimated the incremental cost-effectiveness ratio (ICER) of the cost per additional screen.At 6 months, average costs for intervention and control patients were $37 (25% screened) and $34 (19% screened), respectively. The ICER at 6 months was $42 per additional screen, less than half what other studies have reported. Cost-effectiveness probability was 0.49, 0.84, and 0.99 for willingness-to-pay thresholds of $40, $100, and $200, respectively. Similar results were seen at 9 months. A greater increase in FOBT testing was seen for patients aged70 years (45/100 intervention, 33/100 control) compared with younger patients (25/100 intervention, 21/100 control). The intervention was dominant for patients aged70 years and was $73 per additional screen for younger patients. It increased screening rates by about 6% and costs by $3 per patient.At willingness to pay of $100 or more per additional screening test, an automated telephone reminder intervention can be an optimal use of resources.

e18010Background: Financial hardship is common among individuals diagnosed with cancer. The purpose of this study was to evaluate the association between financial hardship and the receipt of neces...

Background Reports on associations between azole antifungal medications and acute liver injury are inconsistent and have not been based on liver-related laboratory tests. We evaluated incidence rates of acute liver injury associated with oral azole antifungals. Methods We conducted a cohort study among Kaiser Permanente Northern California members who initiated an oral azole antifungal in an outpatient setting during 2004-2010. We determined development of: (1) liver aminotransferases >200 U/L, (2) severe acute liver injury (coagulopathy with hyperbilirubinemia), and (3) acute liver failure. We calculated incidence rates of endpoints. Cox regression was used to determine whether chronic liver disease was a risk factor for outcomes. Results Among 195,334 azole initiators (178,879 fluconazole; 14,296 ketoconazole; 1653 itraconazole; 478 voriconazole; 28 posaconazole), incidence rates (events/1000 person-years [95% confidence intervals (CIs)]) of liver aminotransferases >200 U/L were similarly low with fluconazole (13.0 [11.4-14.6]), ketoconazole (19.3 [13.8-26.3]), and itraconazole (24.5 [10.6-48.2]). Rates were higher with voriconazole (181.9 [112.6-278.0]) and posaconazole (191.1 [23.1-690.4]), but comparable. Severe acute liver injury was uncommon with fluconazole (2.0 [1.4-2.7]), ketoconazole (2.9 [1.1-6.3]), and itraconazole (0.0 [0.0-11.2]), but more frequent with voriconazole (16.7 [2.0-60.2]) and posaconazole (93.4 [2.4-520.6]). One patient developed acute liver failure due to ketoconazole. Pre-existing chronic liver disease increased risks of aminotransferases >200 U/L (hazard ratio 4.68 [95% CI, 3.68-5.94]) and severe acute liver injury (hazard ratio 5.62 [95% CI, 2.56-12.35]). Conclusions Rates of acute liver injury were similarly low for fluconazole, ketoconazole, and itraconazole. Events were more common among voriconazole and posaconazole users but were comparable. Pre-existing chronic liver disease increased risk of azole-induced liver injury.

Background There is a growing awareness in primary care of the importance of identifying patients with chronic kidney disease (CKD) so that they can receive appropriate clinical care; one method that has been widely embraced is the use of automated reporting of estimated glomerular filtration rate (eGFR) by clinical laboratories. We undertook a qualitative study to examine how clinicians use eGFR in clinical decision making, patient communication issues, barriers to use of eGFR, and suggestions to improve the clinical usefulness of eGFR reports. Methods Our study used qualitative methods with structured interviews among primary care clinicians including both physicians and allied health providers, recruited from Kaiser Permanente Northwest, a non-profit health maintenance organization. Results We found that clinicians generally held favorable views toward eGFR reporting but did not use eGFR to replace serum creatinine in their clinical decision-making. Clinicians used eGFR as a tool to help identify CKD, educate patients about their kidney function and make treatment decisions. Barriers noted by several clinicians included a desire for greater education regarding care for patients with CKD and tools to facilitate discussion of eGFR findings with patients. Conclusions The manner in which clinicians use eGFRs appears to be more complex than previously understood, and our study illustrates some of the efforts that might be usefully undertaken (e.g. specific clinician education) when encouraging further promulgation of eGFR reporting and usage.

Background/Aims Improving both awareness and identification of chronic kidney disease (CKD) is important among primary care providers so they can provide appropriate clinical care; one method that has been widely embraced is the use of automated reporting of estimated glomerular filtration rate (eGFR) by clinical laboratories. We undertook a qualitative study to examine how clinicians responded to the onset of automated reporting of eGFR at Kaiser Permanente Northwest (KPNW).

Background: Temporomandibular joint disorders (TMDs) are chronic, often refractory, pain conditions affecting the jaw and face. Patients least likely to respond to allopathic treatment have the most marked biologic responsiveness to external stressors and concomitant psychosocial and emotional difficulties. From a shamanic healing perspective, this describes individuals who are thought to be “dispirited” and may benefit from this ancient form of spiritual healing. Objective: To report on the long-term quantitative and qualitative outcomes relative to end-of-treatment status of a phase I study that evaluated the feasibility and efficacy of shamanic healing for people with TMDs. Methods/Design: Participants were contacted by telephone at one, three, six, and nine months after treatment and asked to report pain and disability outcomes and qualitative feedback. Setting: Portland, OR. Participants: Twenty-three women aged 25 to 55 years diagnosed with TMD. Primary Outcome Measures: Participants rated their TMD-related pain and disability (on the TMD Research Diagnostic Criteria Axis II Pain Related Disability and Psychological Status Scale) at each follow-up call and were asked to describe their condition qualitatively. Results: Improvements in usual pain, worst pain, and functional impairment reported at end of treatment did not change during the 9 months after treatment ended (p > 0.18). Conclusion: Shamanic healing had lasting effects on TMDs in this small cohort of women.

Methods Primary care providers (PCPs) were recruited, stratified on their rates of patient referral to CAM therapies. Acupuncturists and chiropractors were recruited from among those who treated MCO patients, stratified on numbers of MCO patients seen. Patients were recruited from among 11,960 respondents to a questionnaire on use of acupuncture and chiropractic for chronic pain, stratified on patterns of acupuncture and chiropractic use. Providers (CAM and conventional) participated in individual qualitative interviews. Patients participated in focus groups and individual interviews following similar structured guides. Audio from interviews and focus groups were transcribed, and coded. This poster addresses communication and interaction among PCPs, CAM providers, and patients.

To evaluate the effectiveness of an intervention based on health information technology (HIT) that used speech recognition software to promote adherence to inhaled corticosteroids (ICS) among individuals with asthma who were members of a large health maintenance organization.Pragmatic randomized clinical trial.Adults with asthma enrolled in a large managed care organization (N = 8517) were randomized to receive either usual care or an interactive voice recognition (IVR) intervention designed to prompt medication refills and improve ICS adherence. The primary outcome was ICS adherence as measured by modified medication possession ratio calculated from the electronic medical record (EMR). Secondary measures included survey- and EMR-based measures of asthma morbidity.Our primary analyses found that ICS adherence increased modestly but significantly for participants in the intervention group relative to those in the usual care group ( Δ= 0.02, 95% confidence interval 0.01-0.03), with a baseline adherence of 0.42 in both groups. No difference was observed in asthma morbidity measures. In post hoc analyses of participants receiving 2 or more direct IVR contacts or detailed messages, the intervention effect was more marked. The overall effect was triple that observed in the primary analyses (0.06 vs 0.02), and significant differences were observed between groups in asthma control.An HIT-based adherence intervention shows potential for supporting medication adherence in patients with chronic diseases such as asthma. However, additional research is needed to determine how best to enhance the reach and effectiveness of such interventions.

Background: Patient mammogram reminders are effective at increasing screening, but patient barriers remain. We evaluated patient characteristics and reported barriers for their association with mammogram completion after a reminder program. Methods: This retrospective cohort study used data from electronic records and a subgroup survey. Participants were female Kaiser Permanente Northwest health maintenance organization (HMO) members aged 50–69 who were 20 months past their last mammogram (index date) and had received a reminder intervention (n = 4708). A mailed survey was completed by 340 of 667 (50.2%) women who received it. The intervention was a “mammogram due soon” postcard 20 months after the last mammogram, followed by up to two automated phone calls and one live call for nonresponders. The outcome was mammogram completion at 10 months after index date. Results: Characteristics associated with lower mammogram completion rates were aged

Objective: Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). Methods: Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911–2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/ 90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values. Results: The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans.

Background/Aims: Patient mammogram reminders are effective at raising screening rates, but patient screening barriers remain. We evaluated patient characteristics available in electronic medical records that might be associated with mammogram completion after a reminder program, and identified patient-reported barriers that could help to explain response differences. Design: Retrospective cohort study using electronic medical record data and a sub-group patient survey. Setting/Participants: Participants were female Kaiser Permanente Northwest HMO members aged 50–69 who were 20 months past their last mammogram (index date) and who were the target of a reminder intervention (Total N=4,708). A mailed survey was completed by 336 of 665 (50.5%) members of the sub-group that received the survey. Intervention: “Mammogram due soon” post card 20 months after last mammogram, followed by a sequence of up to 2 automated phone calls and 1 live call for non-responders. Main outcome measure: Mammogram completion at 10 months following index date. Results: The characteristics associated with lower mammogram completion rates were age

Although colorectal cancer (CRC) prognosis is improved by early diagnosis, screening rates remain low.To determine the effect of an automated telephone intervention on completion of fecal occult blood testing (FOBT).In this randomized controlled trial conducted at Kaiser Permanente Northwest, a not-for-profit health maintenance organization, 5905 eligible patients aged 51 to 80, at average risk for CRC and due for CRC screening, were randomly assigned to an automated telephone intervention (n = 2943) or usual care (UC; n = 2962). The intervention group received up to three 1-minute automated telephone calls that provided a description and health benefits of FOBT. During the call, patients could request that an FOBT kit be mailed to their home. Those who requested but did not return the cards received an automated reminder call. Cox proportional hazard method was used to determine the independent effect of automated telephone calls on completion of an FOBT, after adjusting for age, sex, and prior CRC screening.By 6 months after call initiation, 22.5% in the intervention and 16.0% in UC had completed an FOBT. Those in the intervention group were significantly more likely to complete an FOBT (hazard ratio, 1.31; 95% confidence interval, 1.10-1.56) compared with UC. Older patients (aged 71-80 vs. aged 51-60) were also more likely to complete FOBT (hazard ratio, 1.48; 95% confidence interval, 1.07-2.04).Automated telephone calls increased completion of FOBT. Further research is needed to evaluate automated telephone interventions among diverse populations and in other clinical settings.

Background/Aims: This retrospective cohort study evaluated the effectiveness of implementation and maintenance phases of a multimodal reminder program to improve routine mammography screening. Methods: The program used automated reminder calls and was conducted at Kaiser Permanente Northwest, a nonprofit group-model HMO with an electronic medical record. Study participants were women HMO members aged 42 or older who were 20 months past their last mammogram (index date) during three time periods: pre-reminder (2004), post-reminder implementation phase (2006), and post-reminder maintenance phase (Jan 1–July 1, 2007) (Total n=35,104). The program targeted women aged 50–69 with a mammogram due followed by post card, followed by up to 2 automated phone calls and 1 live call for non-responders. Women aged 42–49 (for whom clinical guidelines also recommend mammography) receiving no reminders constituted the primary comparison group (CG 1). The primary outcome was time until mammogram in the 10 months following the index date. Results: Pre-reminder, 63.4% of targeted women completed a mammogram; this number increased to 75.4% in the post-reminder implementation; 80.6% completed a mammogram in the maintenance phases. After controlling for demographics and clinic visits, intervention women were 1.51 times more likely to complete a mammogram (CI 1.40–1.62) post-reminder implementation, compared to CG 1. The effect was maintained in 2007 (HR 1.81 [CI 1.65–1.99]). Women of other races (Asian, Pacific Island, or Native American) were less likely to complete a mammogram, as were those taking a greater number of medications. Women with a college education, who were married, or who had visited a primary care provider or gynecologist during follow-up were more likely to complete a mammogram. Conclusions: We found that a multimodal reminder system could be effectively implemented and maintained in a large health system. If widely implemented, this intervention could substantially improve community mammography screening rates. Insured patients who are sicker, or who are of Asian, Pacific Island, or Native American descent may need more support to complete screening. Future studies should address practice-based factors that assist patients in completing mammograms, as well as other factors that affect the reach and cost-effectiveness of delivering the intervention to diverse patient groups.

The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 +/- SE = 0.38 +/- 0.09, P < 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24-q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.

Ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) is a positional candidate gene at chromosome 6q23 where we previously detected strong linkage with fasting-specific plasma insulin and obesity in Mexican Americans from the San Antonio Family Diabetes Study (SAFDS). We genotyped 106 single-nucleotide polymorphisms (SNPs) within ENPP1 in all 439 subjects from the linkage study, and measured association with obesity and metabolic syndrome (MS)-related traits. Of 72 polymorphic SNPs, 24 were associated, using an additive model, with at least one of eight key metabolic traits. Three traits were associated with at least four SNPs. They were high-density lipoprotein cholesterol (HDL-C), leptin, and fasting plasma glucose (FPG). HDL-C was associated with seven SNPs, of which the two most significant P values were 0.0068 and 0.0096. All SNPs and SNP combinations were analyzed for functional contribution to the traits using the Bayesian quantitative-trait nucleotide (BQTN) approach. With this SNP-prioritization analysis, HDL-C was the most strongly associated trait in a four-SNP model (P = 0.00008). After accounting for multiple testing, we conclude that ENPP1 is not a major contributor to our previous linkage peak with MS-related traits in Mexican Americans. However, these results indicate that ENPP1 is a genetic determinant of these traits in this population, and are consistent with multiple positive association findings in independent studies in diverse human populations.

Numerous functional risk factors are associated with the occurrence of secondary amenorrhea in young women. Less is known regarding factors associated with the more prevalent problem of oligomenorrhea. We have evaluated nutrient intake, body composition, perceived psychological stress, 24-hour urinary cortisol, and urinary C peptide (UCP) in 35 eumenorrheic, 11 mildly oligomenorrheic, and 10 oligomenorrheic nonathletic undergraduate women. Nutrient intake was evaluated by a validated food frequency questionnaire. Oligomenorrheic women were found to consume significantly more dietary fiber, crude fiber, and polyunsaturated fat, and significantly less saturated fat than their eumenorrheic classmates. Oligomenorrheic women had significantly lower 24-hour UCP excretion than mildly oligomenorrheic women. The groups did not differ in any aspect of body composition, body weight, age of menarche, perceived psychological stress, or urinary cortisol excretion. The data suggest that higher intake of fiber and lower intake of saturated fat may be associated with oligomenorrhea among otherwise healthy undergraduate nonathletic women.

The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs 8-oxo-2-deoxyguanosine residue (8-oxodG) an oxidatively damaged promutagenic base. Genetic variations in OGG1 gene have been shown to modulate DNA repair capacity and are related risk of tumor development. However, epidemiologic findings have been inconsistent. The purpose of this study is to determine whether genetic variants in OGG1 play a role in susceptibility to angiomyolipoma, a benign kidney tumor associated with tuberous sclerosis complex (TSC) patients. To identify genetic variations, all seven exons of the OGG1 gene were amplified by PCR and sequenced in 22 TSC patients with angiomyolipoma (cases) and 18 controls. By direct sequencing, we identified four missense mutations in OGG1: Arg(45)Gln, Ala(85)Ser, Arg(229)Gln and Ser(326)Cys. Genotypic association with angiomyolipoma was performed using the measured genotype approach as implemented in the variance component analytical tools. Association analysis showed the presence of significant association (p = 0.01) only between the Ser(326)Cys polymorphism of OGG1 and angiomyolipoma. We also assessed the presence of oxidative DNA damage in kidney section from normal healthy subjects, normal kidney tissue from TSC patients and kidney angiomyolipoma tissue from TSC patients by immunostaining for 8-oxodG. 8-OxodG staining was highly abundant in kidney angiomyolipoma tissue from TSC patients compared to weak staining in uninvolved tissue from the same TSC patients or normal kidney from healthy subjects. Taken together, our findings suggest that Ser(326)Cys variant of OGG1 may confer risk for development of angiomyolipomas by increasing oxidative DNA damage.

Objective To present a case report of fatal colon cancer in a young, previously healthy woman 4 years after repeated ovarian stimulation for egg donation, review previous publications on the risks of ovarian stimulation, and make recommendations for further egg donor follow-up, research, and actions by professional associations and regulatory agencies. Design Case report and review of the literature. Setting Case report and review of the literature. Patient(s) One patient and published cases. Intervention(s) None. Main Outcome Measure(s) None. Result(s) There has been no systematic study of the long-term risk of cancer or other adverse outcomes in healthy egg donors. Conclusion(s) At present, potential egg donors cannot give truly informed consent because insufficient information exists about their long-term risks.

We examined the genetic association of neuropeptide Y receptor Y5 (NPY5R) single nucleotide polymorphisms (SNPs) with measures of the insulin resistance (metabolic) syndrome. We genotyped 10 NPY5R SNPs in 439 Mexican American individuals (age=43.3+/-17.3 years and BMI=30.0+/-6.7 kg/m2) distributed across 27 pedigrees from the San Antonio Family Diabetes Study and performed association analyses using the measured genotype approach as implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Minor alleles for five (rs11100493, rs12501691, P1, rs11100494, rs12512687) of the NPY5R SNPs were found to be significantly (p0.05) associated with fasting plasma triglyceride concentrations and decreased high-density lipoprotein concentrations. In addition, the minor allele for SNP P2 was significantly associated (p=0.031) with a decreased homeostasis model assessment of beta-cell function (HOMA-%beta). Linkage disequilibrium between SNP pairs indicated one haplotype block of five SNPs (rs11100493, rs12501691, P1, rs11100494, rs12512687) that were highly correlated (r20.98). These preliminary results provide evidence for association of SNPs in the NPY5R gene with dyslipidemia (elevated triglyceride concentrations and reduced high-density lipoprotein levels) in our Mexican American population.

Regain of weight after initial weight loss constitutes a major factor contributing to the escalating obesity epidemic. The objective of this study was to determine the feasibility and clinical impact of two mind-body interventions for weight-loss maintenance.Randomized, balanced, controlled trial.Large-group model health maintenance organization.Overweight and obese adults were recruited to a 12-week behavioral weight-loss program. Participants meeting threshold weight loss and attendance requirements were eligible for randomization.The three weight-loss maintenance interventions were qigong (QI), Tapas Acupressure Technique (TAT (registered trademark of Tapas Fleming, L.Ac.), and a self-directed support (SDS) group as an attention control.The main outcome measure was weight loss maintenance at 24 weeks postrandomization. Patient interviews explored additional benefits of the interventions, as well as barriers and facilitators to compliance.Eighty-eight percent (88%) of randomized patients completed the study. There were no significant study-related adverse events. At 24 weeks, the TAT group maintained 1.2 kg more weight loss than the SDS group did (p = 0.09), and 2.8 kg more weight loss than the QI group did (p = 0.00), only regaining 0.1 kg. A separation test (0.05 level, 0.95 power) indicated that TAT merits further study. A secondary analysis revealed that participants reporting a previous history of recurrent unsuccessful weight loss were more likely to regain weight if assigned to the SDS arm, but this effect was suppressed in both the QI and TAT groups (p = 0.03). Although QI participants reported important general health benefits, the instruction sequence was too brief, given the complexity of the intervention.TAT warrants further research for weight-loss maintenance. Any further research on qigong should use a modification of our protocol.

Background & Aims Medications are a major cause of acute liver failure (ALF) in the United States, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated health care system that approximates a population-based cohort. Methods We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) health care system between January 1, 2004, and December 31, 2010. We included all KPNC members age 18 years and older with 6 months or more of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. Results Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 events (18.8%), antimicrobials in 2 events (6.3%), and miscellaneous medications in 6 events (18.8%). One patient with acetaminophen-induced ALF died (5.6%; 0.06 events/1,000,000 person-years) compared with 3 patients with non–acetaminophen-induced ALF (21.4%; 0.18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06–2.35) and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59–1.63), respectively. Conclusions Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.

BACKGROUND: Streptococcus bovis bacteremia (SBB) has been associated with gastrointestinal (GI) malignancies, namely colorectal cancer. For this reason, screening colonoscopy for SBB patients is recommended in current practice. However, these recommendations are primarily based on data from case reports and case series. AIM: Determine the incidence of gastrointestinal malignancies in patients with SBB in a regional population-based setting. METHODS: We performed a retrospective cohort study on data from January 2000 December 2013 from a regional, integrated healthcare system in Southern California. All adult patients with positive S. bovis blood cultures were identified. New cases of GI malignancy were identified through an internal prospective cancer registry. Incidence rates (IR) of primary GI malignancies (e.g. colorectal, esophageal, gastric, small intestinal, pancreatic, hepatocellular carcinoma, cholangiocarcinoma, gallbladder, and appendiceal) among the SBB patients were compared to the ageand sex-matched reference population. A priori, we planned to evaluate the impact of S. bovis subspecies on the risk of malignancy. Patients were censored based on death, loss to follow-up, or study end. RESULTS: 356 cases (209 male, 58.7%) with a mean follow-up of 8.75 years (3,115 person-years) of SBB were identified, and among these, 54 new cases of primary GI malignancy were identified. The reference population consisted of 13,976,494 patients with a mean follow-up of 2.76 years (38,630,000 person-years), and among these, 33,208 primary GI malignancies developed. The age-sex adjusted incidence rates for the SBB and the reference populations to develop any GI malignancy were 1301.26 per 100,000 (95% CI 700.28-1902.23) and 85.94 per 100,000 (95% CI 84.99-86.89), respectively; the overall standardized incidence rate ratio (SIRR) for risk of any GI malignancy was 15.14 (95% CI 9.54-24.03; p

Objective To improve the health of people with diabetes, it is essential to identify why patients experience extended periods of poor glycemic control before therapeutic intensification. Research design and methods We surveyed 252 primary care providers at Kaiser Permanente Northwest to determine their beliefs about the glycemic goals of their patients, treatment intensification behavior, and barriers to achieving optimal glycemic control. We linked the responses of 149 providers to the health records of their 18 346 patients with diabetes. Results Patient glycemic levels were not related to either individualized glycemic goals or provider intensification behavior. Providers’ beliefs about diabetic treatment and glycated hemoglobin (HbA1c) goals were poorly associated with patient HbA1c levels. Providers identified patients’ resistance to lifestyle behaviors and taking insulin, lack of medication adherence, and psychosocial issues as the main barriers to optimal glycemic control. Lack of time to care for complex patients was also a barrier. Providers who agreed that “current research did not support A1C levels 9% no matter what I do” were 16% more likely to have patients with HbA1c

We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h2) in diabetic (h2 = 0.45, P < 1 × 10−5) and nondiabetic (h2 = 0.36, P < 1 × 10−3) relatives. Genetic correlation (rG = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] = 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD = 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion.

Objective Individual propensity to chronic, low-grade inflammation—a determinant of atherosclerosis-is in part under the control of genetic factors. To identify genes involved in this modulation, we performed a 10 cM genome screen for linkage with plasma C-reactive protein in 38 extended families including 317 non-diabetic and 177 type 2 diabetic family members (2547 relative pairs). Methods and results In a variance component analysis, heritability of CRP values was significant ( h 2 = 0.39, p h 2 = 0.42, p = 0.003) and non-diabetic ( h 2 = 0.34, p = 0.0015) relatives. The strongest evidence of linkage with CRP was on chromosome 5p15, where the LOD score reached genome-wide significance (LOD = 3.41, genome-wide p = 0.013). Both diabetic and non-diabetic family members contributed to linkage at this location. Smaller linkage peaks were detected on chromosomes 5q35 (LOD = 1.35) and 17p11 (LOD = 1.33). When the analysis was restricted to diabetic family members, another peak of moderate intensity (LOD = 2.17) was evident at 3p21. Conclusions A major gene influencing CRP levels appears to be located on chromosome 5p15, with an effect that is independent of diabetes. Another gene on 3p21 may control CRP variation but only in the presence of a diabetic or insulin-resistant environment.

Low birth weight is an important cause of infant mortality and morbidity worldwide. Birth weight has been shown to be inversely correlated with adult complex diseases such as obesity, type-2 diabetes and cardiovascular disease. However, little is known about the genetic factors influencing variation in birth weight and its association with diseases that occur in later life. We, therefore, have performed a genome-wide search to identify genes that influence birth weight in Mexican-Americans using the data from the San Antonio Family Birth Weight Study participants (n=840). Heritability of birth weight was estimated as 72.0+/-8.4% (P0.0001) after adjusting for the effects of sex and term. Multipoint linkage analysis yielded the strongest evidence for linkage of birth weight (LOD=3.7) between the markers D6S1053 and D6S1031 on chromosome 6q. This finding has been replicated (LOD=2.3) in an independent European-American population. Together, these findings provide substantial evidence (LOD(adj)=4.3) for a major locus influencing variation in birth weight. This region harbors positional candidate genes such as chorionic gonadotropin, alpha chain; collagen, type XIX, alpha-1; and protein-tyrosine phosphatase, type 4A, 1 that may play a role in fetal growth and development. In addition, potential evidence for linkage (LODor=1.2) was found on chromosomes 1q, 2q, 3q, 4q, 9p, 19p and 19q with LODs ranging from 1.3 to 2.7. Thus, we have found strong evidence for a major gene on chromosome 6q that influences variation in birth weight in both Mexican- and European-Americans.

Study Objectives: The editing and scoring of actigraphy data are important for calculating variables that describe sleep. Scoring is dependent on marking time points for when a participant got in and out of bed, plus time when the actigraph was removed. This placement of time points is subject to error. We examined interscorer reliability to determine if files scored by 2 different people were comparable. Design: Observational study. Setting: Community-based. Participants: A subset of 36 women taken from the latest biannual visit of the Study of Osteoporotic Fractures. All women had actigraphy data scored by 1 scorer for the Study of Osteoporotic Fractures staff, plus a blinded rescoring by an expert scorer at a different site. Interventions: N/A. Measurements and Results: The outcomes of interest from actigraphy are duration of in-bed interval, total sleep time, sleep latency, sleep efficiency, wake after sleep onset, total nap time, and total daytime minutes of watch removal. Clearly documented actigraphy scoring procedures were used. There were no significant differences between the expert scorer and the study scorer in sleep outcomes (all P values >.16 from a paired t test). There was a small but statistically significant difference between scorers for watch removal times (mean absolute difference 3.4 minutes ± 5.4, P=.02). The intraclass correlation coefficients showed a high level of agreement (range, 0.84-0.99). Conclusions: Even in a large study with 2 scorers, it is possible to use actigraphy as a measure of sleep without introducing interscorer measurement error. Using well-documented scoring and data-gathering procedures are essential for data quality control.

We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants. There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures. Introduction: Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures, potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy. We prospectively tested this hypothesis in the Study of Osteoporotic Fractures (SOF). Materials and Methods: We studied 6295 white women ⩾65 years of age participating in the SOF who were not taking estrogen therapy at baseline. Hip fracture analyses included 708 hip fractures; vertebral fracture analyses included 267 incident vertebral fractures. Baseline serum estradiol and free testosterone values were available in a small subset of participants. Results and Conclusion: There were no significant differences in age, weight, or BMD between the women who underwent postmenopausal oophorectomy (n = 583) and those who did not (n = 5712). Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy. A history of postmenopausal oophorectomy was not associated with an increased risk of hip (hazard ratio [HR] = 1.1; 95% CI = 0.9-1.5) or vertebral fracture (HR = 0.7; 95% CI = 0.5-1.2). The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level (HR = 1.3; 95% CI = 0.5-3.2) or serum free testosterone level (HR = 1.7; 95% CI = 0.8-3.7) to the model. In summary, postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort. These results are in contrast to previous findings, suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully elucidated and that incidental oophorectomy after menopause should still be considered carefully in each potential patient.

The gray, short-tailed opossum, Monodelphis domestica, is the most extensively used, laboratory-bred marsupial resource for basic biologic and biomedical research worldwide. To enhance the research utility of this species, we are building a linkage map, using both anonymous markers and functional gene loci, that will enable the localization of quantitative trait loci (QTL) and provide comparative information regarding the evolution of mammalian and other vertebrate genomes. The current map is composed of 83 loci distributed among eight autosomal linkage groups and the X chromosome. The autosomal linkage groups appear to encompass a very large portion of the genome, yet span a sex-average distance of only 633.0 cM, making this the most compact linkage map known among vertebrates. Most surprising, the male map is much larger than the female map (884.6 cM vs. 443.1 cM), a pattern contrary to that in eutherian mammals and other vertebrates. The finding of genome-wide reduction in female recombination in M. domestica, coupled with recombination data from two other, distantly related marsupial species, suggests that reduced female recombination might be a widespread metatherian attribute. We discuss possible explanations for reduced female recombination in marsupials as a consequence of the metatherian characteristic of determinate paternal X chromosome inactivation.

We performed a genome scan using BMD data of the forearm and hip on 664 individuals in 29 Mexican-American families. We obtained evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men.The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families.We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available.We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women.These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252

Osteoporosis is a major cause of disability in the United States. Numerous factors contribute to the decline in bone mineral density (BMD) that characterizes this disease, and the importance of heredity is now widely appreciated. We evaluated the joint contributions of genes and environmental factors on variation in BMD in 895 participants of the San Antonio Family Osteoporosis Study (SAFOS). Participants of the SAFOS ranged in age from 18 to 96 years and were members of 34 large families of Mexican American ancestry. BMD was measured at the spine, hip, and forearm by dual-energy X-ray absorptiometry. Information about medical history, lifestyle habits, dietary intake, and physical activity patterns was obtained by questionnaire. Age and body mass index were strongly associated with BMD at nearly every site; these and other measured risk factors accounted in aggregate for up to 46% of the total variation in BMD. In general, the environmental risk factors accounted for proportionately more of the total variation in BMD in men than in women. Genes accounted for 65–80% of the residual variation in spine and hip BMD, and 25–55% of the residual variability in forearm BMD. Although residual heritabilities were generally comparable between men and women across all ages combined, heritabilities at all sites tended to be higher in premenopausal women than in men younger than 50 years of age. Identifying the individual genes involved will shed insights into the processes that govern bone remodeling and may suggest strategies for the prevention of osteoporosis.

Background. Our purpose was to determine whether type 2 diabetes is associated with altered bone mineral density (BMD) and whether fasting serum insulin levels are correlated with BMD. Methods. In a population-based family study of Mexican-Americans, we obtained measurements of BMD, diabetes status (by 2-h oral glucose tolerance test), obesity, and serum insulin concentrations in 600 subjects from 34 families. Analyses were stratified by sex and conditioned on the pedigree structure to account for residual correlations among related individuals. Results. Women with diabetes had significantly higher BMD at hip than women without diabetes (p 0.03) even after adjustment for age, body mass index (BMI), and menopause status. BMD at spine was also higher in diabetic women than in nondiabetic women, although the association was no longer statistically significant after adjustment for BMI. Diabetes was not associated with BMD in men. In nondiabetic men and women, insulin levels were significantly correlated with BMD after adjustment for age and other lifestyle covariates, but correlations were diminished and were no longer statistically significant after further adjustment for body mass index. Conclusions. These results suggest that Mexican-American women with type 2 diabetes have higher BMD compared to their nondiabetic counterparts, with the association independent of obesity at hip, although not at spine or forearm. Increased BMD was also correlated with serum insulin levels, although this association was not independent of obesity. Longitudinal studies may be required to better define the mechanisms underlying the observed association between BMD and diabetes. 2003 IMSS. Published by Elsevier Inc.

The Oregon Center for Complementary and Alternative Medicine (OCCAM) conducted focus groups with participants to determine willingness to join a complementary and alternative medicine (CAM) research study, and to aid in the design of three clinical randomized controlled trials (RCTs) of CAM and craniofacial disorders.Center for Health Research, Kaiser Permanente, in Portland, Oregon.Kaiser Permanente health plan members meeting RCT inclusion criteria.Twelve (12) focus groups were conducted with a total of 85 participants. Six (6) of the focus groups were with members who self-identified as users of CAM therapies. Focus groups explored participants' experiences of CAM for temporomandibular disorder (TMD) and periodontal disease, and their reactions to proposed aspects of the trials. Trained facilitators led the focus groups, which lasted approximately 2 hours and were audiotaped for future transcription. Researchers then coded the transcripts to identify responses to specific questions and to capture emergent themes.Acupuncture, chiropractic, and massage were most frequently accessed and reported as helpful by participants. Participants who had not used CAM treatments for their condition expressed interest and openness to experiencing CAM treatments through a research study. In general, participants expressed willingness to be randomly assigned to (rather than choose) a CAM treatment arm. Travel to practitioners' offices and frequent (1 per week) visits were acceptable to most participants, if there was flexibility in appointment scheduling.Findings indicate considerable willingness to engage in CAM trials, even among individuals who have not used CAM. Participants' willingness to engage in CAM studies was influenced by the nature of their condition, their prior experiences with conventional and CAM treatments, and the possibility of experiencing CAM "for free" through participation in the trial. Their acceptance also was tempered by concerns about particular modalities and the possibility of having to give up aspects of their current health routine. Researchers engaging in CAM studies should take these factors into consideration as they design studies.

Serum LDL cholesterol (LDLC) concentrations and ACE activities are risk factors for the development of cardiovascular disease (CVD). However, the relationship between ACE and CVD susceptibility, and possible mechanisms of action, is controversial. With data on 622 pedigreed baboons, we used statistical genetic methods to determine the mode of inheritance of ACE activities and its relationship to LDLC on different diets. ACE activity was moderately heritable, and quantitative trait linkage analyses detected a quantitative trait locus (QTL) for ACE activity on the baboon homolog of human chromosome 17 (near the ACE structural locus, maximum multipoint lod=7.5, genomic P =0.000003). Bivariate analyses revealed that ACE activity was genetically correlated (ρ G ) with LDLC response (LDLC RC ) to a high-cholesterol diet (ρ G =0.30±0.13, P =0.01) but not to LDLC on a basal diet (ρ G =0.08±0.13). Bivariate genetic analyses indicated that a previously detected QTL for LDLC RC had significant ( P =0.025) pleiotropic effects on ACE activity levels and accounted for the genetic correlation. Therefore, we have detected 2 putative loci that affect ACE activity in baboons, one of which also affects LDLC dietary response. The existence of at least 2 genes that affect ACE activity, one of which is diet-responsive, may help explain the lack of consistency among studies of the relationship between ACE and CVD.

years’ supply of H2RAs (without any PPI use), and 21 749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13 210 (7.2%) were dispense da2o rmore years’ supply of PPIs, 5897 (3.2%) were dispense da2o r more years’ supply of H2RAs (without any PPI use), and 165 092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Bot ha2o rmore years’ supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) an da2o rmore years’ supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction). CONCLUSIONS AND RELEVANCE Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.

Variance component methods are now being used in linkage analysis to detect genes influencing complex diseases. These methods are easily extended to allow for simultaneous estimation of both the additive effects of multiple loci on phenotypic variation (conditional oligogenic analysis) and the additive interaction (epistatic) effects among loci. We performed linkage analyses on 200 of the simulated replicates in order to evaluate the power to detect the main effects of MG1 and MG2 on Q1 as well as their interaction effects. The power to detect the main effect of MG1 was moderately good, although the power to detect MG2 and the MG1 x MG2 interaction was poor.

concordance between these scores when both measures could be computed. Results: We identified 122,270 eligible patients. Of these, 59.7% (n=73,023) had sufficient data to calculate the lab-based risk score and 88.1% (102,795) clinic-based risk score. Neither score could be calculated for 14.5% (n=17,732). The most common reason for not being able to calculate was missing data on cholesterol. Using the laboratory-based score only, we found 12.9% of the population were at high risk (risk >20%), 24.5% moderate risk (10-20%), and 62.6% low risk (