Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. METHODS In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. RESULTS Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. INTERPRETATION Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. FUNDING Roche and the University of Bern.

Antimicrobial drug use and risk factors associated with treatment incidence and mortality in Swiss veal calves reared under improved welfare conditions

Ninety-one Swiss veal farms producing under a label with improved welfare standards were visited between August and December 2014 to investigate risk factors related to antimicrobial drug use and mortality. All herds consisted of own and purchased calves, with a median of 77.4% of purchased calves. The calves' mean age was 29±15days at purchasing and the fattening period lasted at average 120±28 days. The mean carcass weight was 125±12kg. A mean of 58±33 calves were fattened per farm and year, and purchased calves were bought from a mean of 20±17 farms of origin. Antimicrobial drug treatment incidence was calculated with the defined daily dose methodology. The mean treatment incidence (TIADD) was 21±15 daily doses per calf and year. The mean mortality risk was 4.1%, calves died at a mean age of 94±50 days, and the main causes of death were bovine respiratory disease (BRD, 50%) and gastro-intestinal disease (33%). Two multivariable models were constructed, for antimicrobial drug treatment incidence (53 farms) and mortality (91 farms). No quarantine, shared air space for several groups of calves, and no clinical examination upon arrival at the farm were associated with increased antimicrobial treatment incidence. Maximum group size and weight differences >100kg within a group were associated with increased mortality risk, while vaccination and beef breed were associated with decreased mortality risk. The majority of antimicrobial treatments (84.6%) were given as group treatments with oral powder fed through an automatic milk feeding system. Combination products containing chlortetracycline with tylosin and sulfadimidine or with spiramycin were used for 54.9%, and amoxicillin for 43.7% of the oral group treatments. The main indication for individual treatment was BRD (73%). The mean age at the time of treatment was 51 days, corresponding to an estimated weight of 80-100kg. Individual treatments were mainly applied through injections (88.5%), and included administration of fluoroquinolones in 38.3%, penicillines (amoxicillin or benzylpenicillin) in 25.6%, macrolides in 13.1%, tetracyclines in 12.0%, 3th and 4th generation cephalosporines in 4.7%, and florfenicol in 3.9% of the cases. The present study allowed for identifying risk factors for increased antimicrobial drug treatment and mortality. This is an important basis for future studies aiming at reducing treatment incidence and mortality in veal farms. Our results indicate that improvement is needed in the selection of drugs for the treatment of veal calves according to the principles of prudent use of antibiotics.

ANTIBODY-DEPENDENT AND ANTIBODY-INDEPENDENT CELLULAR CYTOTOXICITY AGAINST SHIGELLA

Diarrhea is a major cause of morbidity and mortality worldwide. Shigella causes up to 20% of all diarrhea. Gut-level immunity and breast-feeding of infants are important factors in protection against shigellosis. The lumen of the gut is lined with lymphocytes which mediate natural killer cytotoxicity, NKC, and antibody-dependent cellular cytotoxicity, ADCC. NKC and ADCC are extracellular, nonphagocytic leukocyte killing mechanisms, which occur in the absence of complement, without prior antigen stimulation, and without regard to the major histocompatibility complex. In this study, virulent and avirulent shigellae were used as the target cells. Leukocytes from peripheral blood, breast milk, and guinea pig gut-associated tissues were used as effector cells. Adult human peripheral blood mononuclear cells and lymphocytes, but not macrophages or polymorphonuclear leukocytes, mediated NKC and ADCC at an optimal effector to target cell ratio of 100:1 in a 60 minute bactericidal assay. An antiserum dilution of 1:10 was optimal for ADCC. Whole, viable lymphocytes were necessary for cytotoxicity. Lymphocyte NKC, but not ADCC, was greatly enhanced by interferon. Lymphocyte NKC occurred against several virulent strains of S. sonnei and a virulent strain of S. flexneri. ADCC (using immune serum directed against S. sonnei) occurred against virulent S. sonnei, but not against avirulent S. sonnei or virulent S. flexneri. Lymphocyte ADCC was not inhibited by the presence of phenylbutazone or by pretreatment of lymphocytes with anti-HNK serum plus complement. Both adherent and non-adherent breast milk leukocytes mediated NKC and ADCC. Mononuclear cells from young children demonstrated normal ADCC, when compared to ADCC of adult cells. Neonatal cord blood and a CGD patient's peripheral blood mononuclear and ploymorphonuclear cells demonstrated high ADCC compared to adult cells. Intraepithelial lymphocytes, spleen cells, and peritoneal cells from normal guinea pigs demonstrated NKC and ADCC. Animals which had been starved and opiated were made susceptible to infection by Shigella. The susceptible animals demonstrated deficient NKC and ADCC with all three leukocyte populations. High NKC and ADCC activity of gut-associated leukocytes from human breast milk and guinea pig tissues may correlate with resistance to infection. ^

The genetic basis of thoracic aortic aneurysms and dissections: Genetic heterogeneity and mapping of TAAD1 and TAAD2 loci

Thoracic aortic aneurysms leading to aortic dissections (TAAD) are a major cause of morbidity and mortality in the United States. TAAD is a complication of some known genetic disorders, such as Marfan syndrome and Turner syndrome, but the majority of familial cases are not due to a known genetic syndrome. Previous studies by our group have established that nonsyndromic, familial TAAD is inherited in an autosomal dominant manner with decreased penetrance and variable expression. Using one large family with multiple members with TAAD for the genome wide scan, a major locus for familial TAAD was mapped to 5q13–14 (TAAD1). Nine out of 15 families studied were linked to this locus, establishing that TAAD1 was a major locus, and that there was genetic heterogeneity for the condition. Mapping of TAAD2 locus was accomplished using a single large family with multiple members with TAAD not linked to known loci of aneurysm formation. This established a second novel locus for familial TAAD on 3p24–25 (LOD score of 4.3), termed the TAAD2 locus. Two putative loci with suggestive LOD scores were mapped on 4q and 12q through a genome scan carried out using three families. TAAD phenotype in 12 families did not segregate with known loci, indicating further genetic heterogeneity. An STS-tagged BAC based contig was constructed for 7.8Mb and 25Mb critical interval of TAAD1 and TAAD2 respectively and characterized to identify the defective gene. The hypothesis that the defective genes responsible for the TAAD1 and TAAD2 encoded extracellular matrix (ECM) proteins, the major components of the elastic fiber system in the aortic media was tested. Four genes encoding ECM proteins, versican, thrombospondin-3, CRTL1, on TAAD1 and FBLN2 at TAAD2 were sequenced, but no disease-causing mutations were identified. Studies to identify the defective gene are initiated through the positional candidate gene approach using combination of bioinformatics and expression studies. The identification of the TAAD susceptibility genes will allow for presymptomatic diagnosis of individuals at risk for this life threatening disease. The identification of the molecular defects that contribute to TAAD will also further our understanding of the proteins that provide structural integrity to the aortic wall. ^

Receptor tyrosine kinase HER2-mediated signaling pathways in metastasis and angiogenesis

Metastasis, the major cause of morbidity and mortality in most cancers, is a highly organized and organ-selective process. The receptor tyrosine kinase HER2 enhances tumor metastasis, however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the malignant cancer cells to specific organs. Here we show that HER2 enhances the expression of CXCR4 by increasing CXCR4 protein synthesis and inhibiting its degradation. We also observed significant correlation between HER2 and CXCR4 expression in human breast tumor tissues, and an association between CXCR4 expression and a poor overall survival rate in patients with breast cancer. Furthermore, we found that CXCR4 is required for HER2-induced invasion, migration, and adhesion activities in vitro . Finally we established stable transfectants using retroviral RNA interference to inhibit CXCR4 expression and showed that the CXCR4 is required for HER2-mediated lung metastasis in vivo. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and homing to metastatic organs, and establish a functional link between the receptor tyrosine kinase HER2 and the chemokine receptor CXCR4 signaling pathways. ^ The HER2 overexpression activates PI-3K/Akt pathways and plays an important role in mediating cell survival and tumor development. Hypoxia inducible factors (HIF) are the key regulator for angiogenesis and energy metabolism, and thereby enhance tumor growth and metastasis. HIF activation occurs in the majority of human cancers, including the HER2 overexpressing cancer cells. Previous reports suggested that increased PI-3K/Akt may activate HIF pathway in various tumors, but the detail mechanism is still not completely understood. Here we found that HER2/PI-3K/Akt pathway induces HIF-1α activation, which is independent of hypoxia, but relatively weaker than hypoxic stimulation. This phenomenon was further observed in Akt knock out mouse embryonic fibroblast cells. The PI-3K/Akt pathway does not affect HIF-1α binding with its E3 ligase VHL, but enhances the binding affinity between HIF-1α and β unit. Furthermore, we found Akt phosphorylates HIF-1β at serine 271 and further regulated HIF transcriptional activity. Our findings provided one mechanism that HER2 induce HIF activation via Akt to promote angiogenesis, and this process is independent on hypoxia, which may have implications in the oncogenic activity of HER2 and PI-3K/Akt pathway. ^

The role of the experience and expression of anger in future cardiovascular profiles in young adolescents

Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

Clinical factors associated with growth and mortality of pediatric patients on HAART at Mulago PIDC, Uganda, 2003--2006

The global social and economic burden of HIV/AIDS is great, with over forty million people reported to be living with HIV/AIDS at the end of 2005; two million of these are children from birth to 15 years of age. Antiretroviral therapy has been shown to improve growth and survival of HIV-infected individuals. The purpose of this study is to describe a cohort of HIV-infected pediatric patients and assess the association between clinical factors, with growth and mortality outcomes. ^ This was a historical cohort study. Medical records of infants and children receiving HIV care at Mulago Pediatric Infectious Disease Clinic (PIDC) in Uganda between July 2003 and March 2006 were analyzed. Height and weight measurements were age and sex standardized to Centers for Disease Control and prevention (CDC) 2000 reference. Descriptive and logistic regression analyses were performed to identify covariates associated with risk of stunting or being underweight, and mortality. Longitudinal regression analysis with a mixed model using autoregressive covariance structure was used to compare change in height and weight before and after initiation of highly active antiretroviral therapy (HAART). ^ The study population was comprised of 1059 patients 0-20 years of age, the majority of whom were aged thirteen years and below (74.6%). Mean height-for-age before initiation of HAART was in the 10th percentile, mean weight-for-age was in the 8th percentile, and the mean weight-for-height was in the 23rd percentile. Initiation of HAART resulted in improvement in both the mean standardized weight-for-age Z score and weight-for-age percentiles (p <0.001). Baseline age, and weight-for-age Z score were associated with stunting (p <0.001). A negative weight-for-age Z score was associated with stunting (OR 4.60, CI 3.04-5.49). Risk of death decreased from 84% in the >2-8 years age category to 21% in the >13 years age category respectively, compared to the 0-2 years of age (p <0.05). ^ This pediatric population gained weight significantly more rapidly than height after starting HAART. A low weight-for-age Z score was associated with poor survival in children. These findings suggest that age, weight, and height measurements be monitored closely at Mulago PIDC. ^

The preparticipation sports physical examination and wilderness athletes

Every fifth unintentional injury treated at a healthcare facility in industrialized nations is associated with sports or physical exercise. Though the benefits of exercise on health status are well documented and, for most individuals, far outweigh the risks, participation in sports and exercise programs does carry a risk of injury, illness, or even death. In an effort to decrease these risks most institutions in the United States, and in the industrialized world, require a pre-participation physical examination for all athletes competing in organized or scholastic sports or exercise programs. Over the last ten years the popularity of outdoor or wilderness sports has increased enormously. Traditional outdoor sports such as skiing and hiking are more popular than ever and sports that did not exist 10 to 15 years ago, such as adventure racing or mountain biking, are now multimillion dollar enterprises. This genre of sport appeals to a broad spectrum of individuals and combines the traditional risks of physical activity and exertion with the remoteness and exposure associated with wilderness environments. Wilderness athletes include people of all ages and of both genders. The main causes of morbidity are musculoskeletal injuries and gastrointestinal illnesses; the main causes of mortality are falls and cardiac events. By placing these causes in a Haddon Matrix, preventative strategies have been found and recommendations made specifically for the preparticipation physical examination, which include education about the causes of morbidity and mortality in wilderness athletes, instruction about preventing and treating these injuries and illnesses, and screening of athletes at risk for cardiovascular accidents. Through these measures the risk of injuries, illnesses and deaths in wilderness athletes can be decreased through out the world. ^

Factor H variant Y402H and the prevalence of hypertension and proteinuria: The Atherosclerosis Risk in Communities study

Hypertension is a significant risk factor for cardiovascular disease, which in turn is a major cause of morbidity and mortality worldwide. While the pathogenesis of vascular injury and subsequent end organ damage is complex, there is emerging data to support a role for the complement system in endovascular diseases. The complement Factor H Y402H polymorphism has been associated with a number of vasculopathies, including age-related macular degeneration (AMD), ischemic stroke and myocardial infarction. The current study evaluated the relationship of the Y402H polymorphism with hypertension and microalbuminuria in large the bi-racial Atherosclerosis Risk in Communities (ARIC) study. The Y402H polymorphism was found to be associated with a 48% (p-value 0.042) increase in the risk of developing incident hypertension in African American participants. No significant association was found with the Y402H polymorphism and microalbuminuria. The results from this investigation reveal the first association of the Factor H Y402H polymorphism and an increased risk of incident hypertension in African Americans. ^

The association of area socioeconomic status and cancer screening: A systematic review and multilevel study

Background. The gap between actual and ideal rates of routine cancer screening in the U.S., particularly for colorectal cancer screening (CRCS) (1;2), is responsible for an unnecessary burden of morbidity and mortality, particularly for disadvantaged groups. Knowledge about the effects of individual and area influences is being advanced by a growing body of research that has examined the association of area socioeconomic status (SES) and cancer screening after controlling for individual SES. The findings from this emerging and heterogeneous research in the cancer screening literature have been mixed. Moreover, multilevel studies in this area have not yet adequately explored the possibility of differential associations by population subgroup, despite some evidence suggesting gender-specific effects. ^ Objectives and methods. This dissertation reports on a systematic review of studies on the association of area SES and cancer screening and a multilevel study of the association between area SES and CRCS. The specific aims of the systematic review are to: (1) describe the study designs, constructs, methods, and measures; (2) describe the association of area SES and cancer screening; and (3) identify neglected areas of research. ^ The empiric study linked a pooled sample of respondents aged ≥50 years without a personal history of colorectal cancer from the 2003 and 2005 California Health Interview Surveys with a comprehensive set of census-tract level area SES measures from the 2000 U.S. Census. Two-level random intercept models were used to test 2 hypotheses: (1) area SES will be associated with adherence to two modalities of CRCS after controlling for individual SES; and (2) gender will moderate the relationship between area socioeconomic status and adherence to both modalities of CRCS. ^ Results. The systematic review identified 19 eligible studies that demonstrated variability in study designs, methods, constructs, and measures. The majority of tested associations were either not statistically significant or significant and in the positive direction, indicating that as area SES increased, the odds of CRCS increased. The multilevel study demonstrated that while multiple aspects of area SES were associated with CRCS after controlling for individual SES, associations differed by screening modality and in the case of endoscopy, they also differed by gender. ^ Conclusions. Conceptual and methodologic heterogeneity and weaknesses in the literature to date limit definitive conclusions about the underlying relationships between area SES and cancer screening. The multilevel study provided partial support for both hypotheses. Future research should continue to explore the role of gender as a moderating influence with the aim of identifying the mechanisms linking area SES and cancer prevention behaviors. ^

The effect of African Americans' ethnographic paradigms and cultural explanatory model of breast cancer in framing the male partner's attitudes and behaviors about the woman's breast cancer diagnosis

The disparate burden of breast cancer-related morbidity and mortality experienced by African American women compared with women of other races is a topic of intense debate in the medical and public health arenas. The anomaly is consistently attributed to the fact that at diagnosis, a large proportion of African American women have advanced-stage disease. Extensive research has documented the impacts of cultural factors and of socioeconomic factors in shaping African American women's breast-health practices; however, there is another factor of a more subtle influence that might have some role in establishing these women's vulnerability to this disease: the lack of or perceived lack of partner support. Themes expressed in the research literature reflect that many African American breast cancer patients and survivors consider their male partners as being apathetic and nonsupportive. ^ The purpose of this study was to learn how African American couples' ethnographic paradigms and cultural explanatory model of breast cancer frame the male partners' responses to the women's diagnosis and to assess his ability to cope and willingness to adapt to the subsequent challenges. The goal of the study was to determine whether these men's coping and adaptation skills positively or negatively affect the women's self-care attitudes and behaviors. ^ This study involved 4 African American couples in which the woman was a breast cancer survivor. Participants were recruited through a community-based cancer support group and a church-based cancer support group. Recruitment sessions were held at regular meetings of these organizations. Accrual took 2 months. In separate sessions, each male partner and each survivor completed a demographic survey and a questionnaire and were interviewed. Additionally, the couples were asked to participate in a communications activity (Adinkra). This activity was not done to fulfill any part of the study purpose and was not included in the data analysis; rather, it was done to assess its potential use as an intervention to promote dialogue between African American partners about the experience of breast cancer. ^ The questionnaire was analyzed on the basis of a coding schema and the interview responses were analyzed on the principles of hermeneutic phenomenology. In both cases, the instruments were used to determine whether the partner's coping skills reflected a compassionate attitude (positive response) versus an apathetic attitude (negative response) and whether his adaptation skills reflected supportive behaviors (the positive response) versus nonsupportive behaviors (the negative response). Overall, the women's responses showed that they perceived of their partners as being compassionate, yet nonsupportive, and the partner's perceived of themselves likewise. Only half of the women said that their partners' coping and adaptation abilities enabled them to relinquish traditional concepts of control and focus on their own well-being. ^ The themes that emerged indicate that African American men's attitudes and behaviors regarding his female partner's diagnosis of breast cancer and his ability to cope and willingness to adapt are influenced by their ritualistic mantras, folk beliefs, religious teachings/spiritual values, existential ideologies, socioeconomic status, and environmental factors and by their established perceptions of what causes breast cancer, what the treatments and outcomes are, and how the disease affects the entire family, particularly him. These findings imply that a culturally specific intervention might be useful in educating African American men about breast cancer and their roles in supporting their female partners, physically and psychologically, during diagnosis, treatment, and recovery. ^

Diabetes genes and risk of prostate cancer in the Atherosclerosis Risk in Communities study

Prostate cancer (PrCa) is a leading cause of morbidity and mortality, yet the etiology remains uncertain. Meta-analyses show that PrCa risk is reduced by 16% in men with type 2 diabetes (T2D), but the mechanism is unknown. Recent genome-wide association studies and meta-analyses have found single nucleotide polymorphisms (SNPs) that consistently predict T2D risk. We evaluated associations of incident PrCa with 14 T2D SNPs in the Atherosclerosis Risk in Communities (ARIC) study. From 1987-2000, there were 397 incident PrCa cases ascertained from state or local cancer registries among 6,642 men (1,560 blacks and 5,082 whites) aged 45-64 years at baseline. Genotypes were determined by TaqMan assay. Cox proportional hazards models were used to assess the association between PrCa and increasing number of T2D risk-raising alleles for individual SNPs and for genetic risk scores (GRS) comprised of the number of T2D risk-raising alleles across SNPs. Two-way gene-gene interactions were evaluated with likelihood ratio tests. Using additive genetic models, the T2D risk-raising allele was associated with significantly reduced risk of PrCa for IGF2BP2 rs4402960 (hazard ratio [HR]=0.79; P=0.07 among blacks only), SLC2A2 rs5400 (race-adjusted HR=0.85; P=0.05) and UCP2 rs660339 (race-adjusted HR=0.84; P=0.02), but significantly increased risk of PrCa for CAPN10 rs3792267 (race-adjusted HR=1.20; P=0.05). No other SNPs were associated with PrCa using an additive genetic model. However, at least one copy of the T2D risk-raising allele for TCF7L2 rs7903146 was associated with reduced PrCa risk using a dominant genetic model (race-adjusted HR=0.79; P=0.03). These results imply that the T2D-PrCa association may be partly due to shared genetic variation, but these results should be verified since multiple tests were performed. When the combined, additive effects of these SNPs were tested using a GRS, there was nearly a 10% reduction in risk of PrCa per T2D risk-raising allele (race-adjusted HR=0.92; P=0.02). SNPs in IGF2BP2, KCNJ11 and SLC2A2 were also involved in multiple synergistic gene-gene interactions on a multiplicative scale. In conclusion, it appears that the T2D-PrCa association may be due, in part, to common genetic variation. Further knowledge of T2D gene-PrCa mechanisms may improve understanding of PrCa etiology and may inform PrCa prevention and treatment.^

Prevalence and risk factors for human immunodefiency virus and hepatitis C virus co-infection among drug users in innercity neighborhoods in Houston, Texas

Background. There are 200,000 HIV/HCV co-infected people in the US and IDUs are at highest risk of exposure. Between 52-92% of HIV infected IDUs are chronically infected with HCV. African Americans and Hispanics bear the largest burden of co-infections. Furthermore HIV/HCV co-infection is associated with high morbidity and mortality if not treated. The present study investigates the demographic, sexual and drug related risk factors for HIV/HCV co-infection among predominantly African American injecting and non-injecting drug users living in two innercity neighborhoods in Houston, Texas. ^ Methods. This secondary analysis used data collected between February 2004 and June 2005 from 1,889 drug users. Three case-comparison analyses were conducted to investigate the risk factors for HIV/HCV co-infection. HIV mono-infection, HCV mono-infection and non-infection were compared to HIV/HCV co-infection to build multivariate logistic regression models. Race/ethnicity and age were forced into each model regardless of significance in the univariate analysis. ^ Results. The overall prevalence of HIV/HCV co-infection was 3.9% while 39.8% of HIV infected drug users were co-infected with HCV and 10.7% of HCV infected drug users were co-infected with HIV. Among HIV infected IDUs the prevalence of HCV was 71.7% and among HIV infected NIDUs the prevalence of HCV was 24%. In the multivariate analysis, HIV/HCV co-infection was associated with injecting drug use when compared to HIV mono-infection, with MSM when compared to HCV mono-infection and with injecting drug use as well as MSM when compared to non-infection. ^ Conclusion. HIV/HCV co-infection was associated with a combination of sexual and risky injecting practices. More data on the prevalence and risk factors for co-infection among minority populations is urgently needed to support the development of targeted interventions and treatment options. Additionally there should be a focus on promoting safer sex and injecting practices among drug users as well as the expansion of routine testing for HIV and HCV infections in this high risk population.^

Association of left ventricular hypertrophy and stage of hypertension by ambulatory blood pressure monitor

Hypertension in adults is defined by risk for cardiovascular morbidity and mortality, but in children, hypertension is defined using population norms. The diagnosis of hypertension in children and adolescents requires only casual blood pressure measurements, but the use of ambulatory blood pressure monitoring to further evaluate patients with elevated blood pressure has been recommended in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. The aim of this study is to assess the association between stage of hypertension (using both casual and 24 hour ambulatory blood pressure measurements) and target organ damage defined by left ventricular hypertrophy (LVH) in a sample of children and adolescents in Houston, TX. A retrospective analysis was performed on the primary de-identified data from the combination of participants in two, IRB approved, cross-sectional studies. The studies collected basic demographic data, height, weight, casual blood pressures, ambulatory blood pressures, and left ventricular measurements by echocardiography on children age 8 to 18 years old. Hypertension was defined and staged using the criteria for ambulatory blood pressure reported by Lurbe et al. [1] with some modification. Left ventricular hypertrophy was defined using left ventricular mass index (LVMI) criteria specific for children and adults. The pediatric criterion was LVMI2.7 > 95th percentile for gender and the adult criterion was LVMI2.7 > 51g/m2.7. Participants from the original studies were included in this analysis if they had complete demographic information, anthropometric measures, casual blood pressures, ambulatory blood pressures, and echocardiography data. There were 241 children and adolescents included: 19.1% were normotensive, 17.0% had white coat hypertension, 11.6% had masked hypertension, and 52.4% had confirmed hypertension. Of those with hypertension, 22.4% had stage 1 hypertension, 5.8% had stage 2 hypertension, and 24.1% had stage 3 hypertension. Participants with confirmed hypertension were more likely to have LVH by pediatric criterion than those who were normotensive [OR 2.19, 95% CI (1.04–4.63)]; LVH defined by adult criterion did not differ significantly in normotensives compared with hypertensives [OR 2.08, 95% CI (0.58–7.52)]. However, there was a significant trend in the increased prevalence of LVH across the six blood pressure categories for LVH defined by both pediatric and adult criteria (p < 0.001 and p = 0.02, respectively). Additionally, the mean LVM indexed by height 2.7 had a significantly increased trend across blood pressure stages from normal to stage 3 hypertension (p < 0.02). Pediatric hypertension is defined using population norms, and although children with mild hypertension are not at increased odds of having target organ damage defined by LVH, those with severe hypertension are more likely to have LVH. Staging hypertension by ambulatory blood pressure further describes an individual's risk for LVH target organ damage. ^

Cross-cultural equivalence and associations among food insecurity and parental influences of children's fruit and vegetable consumption

Over the past several decades, the prevalence of obesity has dramatically increased. Cause for concern has increased because overweight and obesity are major contributors to morbidity and mortality. Intervention research aimed at reducing the prevalence of obesity has identified the family, specifically the parent, as a key component of the home environment. However, findings from dietary behavior change interventions have been disheartening because few studies have reported meaningful change, suggesting methodological and/or measurement issues within the intervention process. A lack of appropriate mediators and cross-cultural equivalence may partially explain the reason for little change.^ The study aims were to (1) evaluate the psychometric properties and assess the cross cultural equivalence of the Food Insecurity Scale (paper 1) and the modified Parent Feeding Practices Questionnaire (paper 2) and to assess the overall relationships among food insecurity, parent mediators, and parent behaviors towards children's dietary behavior (paper 3) through structural equation modeling and tests of invariance. The study aims were accomplished through conducting secondary analyses using baseline data from English- and Spanish-speaking Hispanic women who participated in the Healthy Families: Step by Step (BHF) study.^ Results indicated that although the FIS and the mPFPQ exhibited sound psychometric properties, the instruments exhibited a lack of invariance across language spoken groups. The lack of invariance was more pronounced in the FIS. Results also supported the theoretical framework identifying parent's perceived barriers and self-efficacy as mediators of parent's behaviors toward improving children's health eating. Results did not suggest that the relationships were moderated by food insecurity.^ In conclusion, the identification of differential item functioning in food insecurity and parent feeding practices may be beneficial in enhancing tailored interventions through the incorporation of cultural differences into the change mechanisms. However, future research needs to be conducted to determine if the lack of invariance demonstrates the existence of item bias or if it is a reflection of true difference among the language spoken groups. Additionally, obesity intervention studies targeting parent/family barriers and parent self-efficacy to provide/encourage healthy diets may result in an increase in parent behaviors which promote healthy eating behaviors among children. Future research should also examine a more complete causal pathway to determine whether parental changes in the mediators ultimately lead to an increase in healthy dietary behavior among children.^