Instrumental variable method for the causal relationship between soluble receptor for advanced glycation end-products (sRAGE) and risk of pancreatic cancer

This thesis project is motivated by the potential problem of using observational data to draw inferences about a causal relationship in observational epidemiology research when controlled randomization is not applicable. Instrumental variable (IV) method is one of the statistical tools to overcome this problem. Mendelian randomization study uses genetic variants as IVs in genetic association study. In this thesis, the IV method, as well as standard logistic and linear regression models, is used to investigate the causal association between risk of pancreatic cancer and the circulating levels of soluble receptor for advanced glycation end-products (sRAGE). Higher levels of serum sRAGE were found to be associated with a lower risk of pancreatic cancer in a previous observational study (255 cases and 485 controls). However, such a novel association may be biased by unknown confounding factors. In a case-control study, we aimed to use the IV approach to confirm or refute this observation in a subset of study subjects for whom the genotyping data were available (178 cases and 177 controls). Two-stage IV method using generalized method of moments-structural mean models (GMM-SMM) was conducted and the relative risk (RR) was calculated. In the first stage analysis, we found that the single nucleotide polymorphism (SNP) rs2070600 of the receptor for advanced glycation end-products (AGER) gene meets all three general assumptions for a genetic IV in examining the causal association between sRAGE and risk of pancreatic cancer. The variant allele of SNP rs2070600 of the AGER gene was associated with lower levels of sRAGE, and it was neither associated with risk of pancreatic cancer, nor with the confounding factors. It was a potential strong IV (F statistic = 29.2). However, in the second stage analysis, the GMM-SMM model failed to converge due to non- concaveness probably because of the small sample size. Therefore, the IV analysis could not support the causality of the association between serum sRAGE levels and risk of pancreatic cancer. Nevertheless, these analyses suggest that rs2070600 was a potentially good genetic IV for testing the causality between the risk of pancreatic cancer and sRAGE levels. A larger sample size is required to conduct a credible IV analysis.^

Physician attitudes on the HPV vaccine

The quadrivalent HPV vaccine was developed primarily for the prevention of cervical cancer. The vaccine, originally approved for females, was recently approved by the American Committee for Immunization Practices to be administered to males, allowing federal programs to pay for the vaccination for both males and females. However, uptake for this vaccination has been low. Studies show that physicians have great influence over whether or not parents decide to vaccinate their children. In this study, a survey was mailed out asking physicians about their attitude towards the HPV vaccination and what they believed to be the barriers to the vaccination of their patients. The analysis of the data included descriptive statistics and chi-square analysis in order to compare the differences in responses between male and female patients. The vast majority of physicians supported the vaccination of both females and males. However, the perceived barriers to vaccinating females differed from males, with physicians believing that parents' concern about sexual promiscuity was a greater barrier to vaccination in girls than boys (p=0.007). The other major significant difference in perceived barriers among physicians is the belief that physicians in general are less likely to promote the vaccination in males compared to females (p=0.01). Despite evidence to the contrary, it seems more patient education is needed regarding sexual promiscuity and its association with the HPV vaccine. There may also be a need for increased physician education regarding the use of the HPV vaccine for male patients.^

Clostridium difficile infection (CDI) in HIV-positive patients

The main aim of this study was to look at the association of Clostridium difficile infection (CDI) and HIV. A secondary goal was to look at the trend of CDI-related deaths in Texas from 1999-2011. To evaluate the coinfection of CDI and HIV, we looked at 2 datasets provided by CHS-TDSHS, for 13 years of study period from 1999-2011: 1) Texas death certificate data and 2) Texas hospital discharge data. An ancillary source of data was national level death data from CDC. We did a secondary data analysis and reported the age-adjusted death rates (mortality) and hospital discharge frequencies (morbidity) for CDI, HIV and for CDI+HIV coinfection.^ Since the turn of the century, CDI has reemerged as an important public health challenge due to the emergence of hypervirulent epidemic strains. From 1999-2011, there has been a significant upward trend in CDI-related death rates; in the state of Texas alone, CDI mortality rate has increased 8.7 fold in this time period at the rate of 0.2 deaths per year per 100,000 individuals. On the contrary, mortality due to HIV has decreased by 46% and has been trending down. The demographic groups in Texas with the highest CDI mortality rates were elderly aged 65+, males, whites and hospital inpatients. The epidemiology of C. difficile has changed in such a way that it is not only staying confined to these traditional high-risk groups, but is also being increasingly reported in low-risk populations such as healthy people in the community (community acquired C. difficile), and most recently immunocompromised patients. Among the latter, HIV can worsen the adverse health outcomes of CDI and vice versa. In patients with CDI and HIV coinfection, higher mortality and morbidity was found in young & middle-aged adults, blacks and males, the same demographic population that is at higher risk for HIV. As with typical CDI, the coinfection was concentrated in the hospital inpatients. Of all the CDI-related deaths in USA from 1999-2010, in the 25-44 year age group, 13% had HIV infection. Of all CDI-related inpatient hospital discharges in Texas from 1999-2011, in patients 44 years and younger, 17% had concomitant HIV infection. Therefore, HIV is a possible novel emerging risk factor for CDI.^

The development of poultry farms risk assessment tool for avian influenza in Imo State, Nigeria

Background: Nigeria was one of the 13 countries where avian influenza outbreak in poultry farms was reported during the 2006 avian influenza pandemic threat and was also the first country in Africa to report the presence of H5N1influenza among its poultry population. There are multiple hypotheses on how the avian influenza outbreak of 2006 was introduced to Nigeria, but the consensus is that once introduced, poultry farms and their workers were responsible for 70% of the spread of avian influenza virus to other poultry farms and the population. ^ The spread of avian influenza has been attributed to lack of compliance by poultry farms and their workers with poultry farm biosecurity measures. When poultry farms fail to adhere to biosecurity measures and there is an outbreak of infectious diseases like in 2006, epidemiological investigations usually assess poultry farm biosecurity—often with the aid of a questionnaire. Despite the importance of questionnaires in determining farm compliance with biosecurity measures, there have been few efforts to determine the validity of questionnaires designed to assess poultry farms risk factors. Hence, this study developed and validated a tool (questionnaire) that can be used for poultry farm risk stratification in Imo State, Nigeria. ^ Methods: Risk domains were generated using literature and recommendations from agricultural organizations and the Nigeria government for poultry farms. The risk domains were then used to develop a questionnaire. Both the risk domain and questionnaire were verified and modified by a group of five experts with a research interest in Nigeria's poultry industry and/or avian influenza prevention. Once a consensus was reached by the experts, the questionnaire was distributed to 30 selected poultry farms in Imo State, Nigeria that participated in this study. Survey responses were received for all the 30 poultry farms that were selected. The same poultry farms were visited one week after they completed the questionnaires for on-site observation. Agreement among survey and observation results were analyzed using a kappa test and rated as poor, fair, moderate, substantial, or nearly perfect; and internal consistency of the survey was also computed. ^ Result: Out of the 43 items on the questionnaire, 32 items were validated by this study. The agreement between the survey result and onsite observation was analyzed using kappa test and ranged from poor to nearly perfect. Most poultry farms had their best agreements in the contact section of the survey. The least agreement was noted in the farm management section of the survey. Thirty-two questions on the survey had a coefficient alpha > 0.70, which is a robust internal consistency for the survey. ^ Conclusion: This study developed 14 risk domains for poultry farms in Nigeria and validated 32 items from the original questionnaire that contained 43 items. The validated items can be used to determine the risk of introduction and spread of avian influenza virus in poultry farms in Imo State, Nigeria. After further validations in other states, regions and poultry farm sectors in Nigeria; this risk assessment tool can then be used to determine the risk profile of poultry farms across Nigeria.^

Optimal, minimax, and Bayesian two-stage designs in two-dose phase II clinical trials

Background: For most cytotoxic and biologic anti-cancer agents, the response rate of the drug is commonly assumed to be non-decreasing with an increasing dose. However, an increasing dose does not always result in an appreciable increase in the response rate. This may especially be true at high doses for a biologic agent. Therefore, in a phase II trial the investigators may be interested in testing the anti-tumor activity of a drug at more than one (often two) doses, instead of only at the maximum tolerated dose (MTD). This way, when the lower dose appears equally effective, this dose can be recommended for further confirmatory testing in a phase III trial under potential long-term toxicity and cost considerations. A common approach to designing such a phase II trial has been to use an independent (e.g., Simon's two-stage) design at each dose ignoring the prior knowledge about the ordering of the response probabilities at the different doses. However, failure to account for this ordering constraint in estimating the response probabilities may result in an inefficient design. In this dissertation, we developed extensions of Simon's optimal and minimax two-stage designs, including both frequentist and Bayesian methods, for two doses that assume ordered response rates between doses. ^ Methods: Optimal and minimax two-stage designs are proposed for phase II clinical trials in settings where the true response rates at two dose levels are ordered. We borrow strength between doses using isotonic regression and control the joint and/or marginal error probabilities. Bayesian two-stage designs are also proposed under a stochastic ordering constraint. ^ Results: Compared to Simon's designs, when controlling the power and type I error at the same levels, the proposed frequentist and Bayesian designs reduce the maximum and expected sample sizes. Most of the proposed designs also increase the probability of early termination when the true response rates are poor. ^ Conclusion: Proposed frequentist and Bayesian designs are superior to Simon's designs in terms of operating characteristics (expected sample size and probability of early termination, when the response rates are poor) Thus, the proposed designs lead to more cost-efficient and ethical trials, and may consequently improve and expedite the drug discovery process. The proposed designs may be extended to designs of multiple group trials and drug combination trials.^

Study on the effect of metformin in patients of metastatic renal cell cancer with diabetes receiving tyrosine kinase inhibitor therapy

Objective: The primary objective of our study was to study the effect of metformin in patients of metastatic renal cell cancer (mRCC) and diabetes who are on treatment with frontline therapy of tyrosine kinase inhibitors. The effect of therapy was described in terms of overall survival and progression free survival. Comparisons were made between group of patients receiving metformin versus group of patients receiving insulin in diabetic patients of metastatic renal cancer on frontline therapy. Exploratory analyses were also done comparing non-diabetic patients of metastatic renal cell cancer receiving frontline therapy compared to diabetic patients of metastatic renal cell cancer receiving metformin therapy. ^ Methods: The study design is a retrospective case series to elaborate the response rate of frontline therapy in combination with metformin for mRCC patients with type 2 diabetes mellitus. The cohort was selected from a database, which was generated for assessing the effect of tyrosine kinase inhibitor therapy associated hypertension in metastatic renal cell cancer at MD Anderson Cancer Center. Patients who had been started on frontline therapy for metastatic renal cell carcinoma from all ethnic and racial backgrounds were selected for the study. The exclusion criteria would be of patients who took frontline therapy for less than 3 months or were lost to follow-up. Our exposure variable was treatment with metformin, which comprised of patients who took metformin for the treatment of type 2 diabetes at any time of diagnosis of metastatic renal cell carcinoma. The outcomes assessed were last available follow-up or date of death for the overall survival and date of progression of disease from their radiological reports for time to progression. The response rates were compared by covariates that are known to be strongly associated with renal cell cancer. ^ Results: For our primary analyses between the insulin and metformin group, there were 82 patients, out of which 50 took insulin therapy and 32 took metformin therapy for type 2 diabetes. For our exploratory analysis, we compared 32 diabetic patients on metformin to 146 non-diabetic patients, not on metformin. Baseline characteristics were compared among the population. The time from the start of treatment until the date of progression of renal cell cancer and date of death or last follow-up were estimated for survival analysis. ^ In our primary analyses, there was a significant difference in the time to progression of patients receiving metformin therapy vs insulin therapy, which was also seen in our exploratory analyses. The median time to progression in primary analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 540 days (95% CI: 350-894) in patients who were receiving insulin therapy (p=0.024). The median time to progression in exploratory analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 279 days (95% CI: 202-372 days) in non-diabetic group (p-value <0.0001). ^ The median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 816 days (95%CI: 558-1405 days) in insulin group (p-value<0.91). For the exploratory analyses, the median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 766 days (95%CI: 649-965 days) in the non-diabetic group (p-value<0.78). Metformin was observed to increase the progression free survival in both the primary and exploratory analyses (HR=0.52 in metformin Vs insulin group and HR=0.36 in metformin Vs non-diabetic group, respectively). ^ Conclusion: In laboratory studies and a few clinical studies metformin has been proven to have dual benefits in patients suffering from cancer and type 2-diabetes via its action on the mammalian target of Rapamycin pathway and effect in decreasing blood sugar by increasing the sensitivity of the insulin receptors to insulin. Several studies in breast cancer patients have documented a beneficial effect (quantified by pathological remission of cancer) of metformin use in patients taking treatment for breast cancer therapy. Combination of metformin therapy in patients taking frontline therapy for renal cell cancer may provide a significant benefit in prolonging the overall survival in patients with metastatic renal cell cancer and diabetes. ^

Assessing the patterns of colorectal cancer treatment, adherence to treatment guidelines and survival in Texas

Colorectal cancer (CRC) is the third leading cancer in both incidence and mortality in Texas. This study investigated the adherence of CRC treatment to standard treatment guidelines and the association between standard treatment and CRC survival in Texas. The author used Texas Cancer Registry (TCR) and Medicare linked data to study the CRC treatment patterns and factors associated with standard treatment in patients who were more than 65 years old and were diagnosed in 2001 through 2007. We also determined whether adherence to standard treatment affect patients' survival. Multiple logistic regression and Cox regression analysis were used to analyze our data. Both regression models are adjusted for demographic characteristics and tumor characteristics. We found that for the 3977 regional colon cancer patients 80 years old or younger, 60.2% of them received chemotherapy, in adherence to the recommended treatment guidelines. People with younger age, female gender, higher education and lower comorbidity score are more likely adherent to this surgery guideline. Patients' adherence to chemotherapy in this cohort have better survival compared to those who are not (HR: 0.76, 95% CI: 0.68-0.84). For the 12709 colon cancer patients treated with surgery, 49.3% have more than 12 lymph nodes removed, in adherence to the treatment guidelines. People with younger age, female gender, higher education, regional stage, lager tumor size and lower comorbidity score are more likely to adherent to this surgery guideline. Patients with more than 12 lymph nodes removed in this cohort have better survival (HR: 0.86, 95% CI: 0.82-0.91). For the 1211 regional rectal cancer patients 80 years old or younger, 63.2% of them were adherent to radiation treatment. People with smaller tumor size and lower comorbidity score are more likely to adherent to this radiation guideline. There is no significant survival difference between radiation adherent patients and non-adherent patients (HR: 1.03, 95% CI: 0.82-1.29). For the 1122 regional rectal cancer patients 80 years old or younger who were treated with surgery, 76.0% of them received postoperative chemotherapy, in adherence to the treatment guidelines. People with younger age and smaller comorbidity score are related with higher adherence rate. Patients adherent with adjuvant chemotherapy in this cohort have better survival than those were not adherent (HR: 0.60, 95% CI: 0.45-0.79).^

A cohort study of body fatness and coronary mortality in middle -aged men

Data from the Chicago Western Electric Study were used to investigate whether central fat distribution, as estimated by the ratio of subscapular-to-triceps skinfold, was associated with 25-year risk of death from coronary heart disease in a cohort of 1,945 middle-aged employed men. Subscapular-triceps skinfold ratio was found positively and significantly associated with risk of coronary death after adjustment for age and body mass index. The age-adjusted proportional hazards regression coefficient was 0.2078 with 95% confidence interval of 0.0087 to 0.4069. A difference of 1.1 in the subscapular-triceps skinfold ratio (the difference between the mean of the fifth quintile and of the first and second quintiles combined) was associated with a relative risk of 1.31 with 95% confidence interval of 1.06 to 1.62. The coefficient was decreased to 0.1961 (95% confidence interval of ($-$0.0028 to 0.3950) after adjustment for diastolic blood pressure, serum cholesterol and cigarette smoking as well as age and body mass index. At least some of the effect of central fat on coronary risk is probably mediated by blood pressure and serum lipids, but whether all of the effect can be accounted for blood pressure and serum lipids is uncertain.^ This study supports the concept that central fat distribution is a risk factor for 25-year risk of coronary death in middle-aged men. ^

Sources of familial aggregation and co-aggregation of fasting blood glucose and nutritional factors among Mexican -Americans in Starr County, Texas

The purpose of this study was to determine the effects of nutrient intake, genetic factors and common household environmental factors on the aggregation of fasting blood glucose among Mexican-Americans in Starr County, Texas. This study was designed to determine: (a) the proportion of variation of fasting blood glucose concentration explained by unmeasured genetic and common household environmental effects; (b) the degree of familial aggregation of measures of nutrient intake; and (c) the extent to which the familial aggregation of fasting blood glucose is explained by nutrient intake and its aggregation. The method of path analysis was employed to determine these various effects.^ Genes play an important role in fasting blood glucose: Genetic variation was found to explain about 40% of the total variation in fasting blood glucose. Common household environmental effects, on the other hand, explained less than 3% of the variation in fasting blood glucose levels among individuals. Common household effects, however, did have significant effects on measures of nutrient intake, though it explained only about 10% of the total variance in nutrient intake. Finally, there was significant familial aggregation of nutrient intake measures, but their aggregation did not contribute significantly to the familial aggregation of fasting blood glucose. These results imply that similarities among relatives for fasting blood glucose are not due to similarities in nutrient intake among relatives. ^

First -year mortality and survival among infants with selected congenital anomalies in Texas, 1995 to 1997

Congenital anomalies have been a leading cause of infant mortality for the past twenty years in the United States. Few registry-based studies have investigated the mortality experience of infants with congenital anomalies. Therefore, a registry-based mortality study was conducted of 2776 infants from the Texas Birth Defects Registry who were born January 1, 1995 to December 31, 1997, with selected congenital anomalies. Infants were matched to linked birth-infant death files from the Texas Department of Health, Bureau of Vital Statistics. One year Kaplan-Meier survival curves, and mortality estimates were generated for each of the 23 anomalies by maternal race/ethnicity, infant sex, birth weight, gestational age, number of life-threatening anomalies, prenatal diagnosis, hospital of birth and other variables. ^ There were 523 deaths within the first year of life (mortality rate = 191.0 per 1,000 infants). Infants with gastroschisis, trisomy 21, and cleft lip ± palate had the highest first year survival (92.91%, 92.32%, and 87.59%, respectively). Anomalies with the lowest survival were anencephaly (5.13%), trisomy 13 (7.41%), and trisomy 18 (10.29%). ^ Infants born to White, Non-Hispanic women had the highest first year survival (83.57%; 95% CI: 80.91, 85.88), followed by African-Americans (82.43%; 95% CI: 76.98, 86.70) and Hispanics (79.28%; 95% CI: 77.19, 81.21). Infants with birth weights ≥2500 grams and gestational ages ≥37 weeks also had the highest first year survival. First year mortality drastically increased as the number of life-threatening anomalies increased. Mortality was also higher for infants with anomalies that were prenatally diagnosed. Slight differences existed in survival based on infant's place of delivery. ^ In logistic regression analysis, birth weight (<1500 grams: OR = 7.48; 95% CI: 5.42, 10.33; 1500–2499 grams: OR = 3.48; 95% CI: 2.74, 4.42), prenatal diagnosis (OR = 1.92; 95% CI: 1.43, 2.58) and number of life-threatening anomalies (≥3: OR = 22.45; 95% CI: 11.67, 43.18) were the strongest predictors of death within the first year of life for all infants with selected congenital anomalies. To achieve further reduction in the infant mortality rate in the United States, additional research is needed to identify ways to reduce mortality among infants with congenital anomalies. ^

Left, right and interval bivariate censored data: Evaluating screening mammography in the presence of lead -time bias, length bias and over-detection

Of the large clinical trials evaluating screening mammography efficacy, none included women ages 75 and older. Recommendations on an upper age limit at which to discontinue screening are based on indirect evidence and are not consistent. Screening mammography is evaluated using observational data from the SEER-Medicare linked database. Measuring the benefit of screening mammography is difficult due to the impact of lead-time bias, length bias and over-detection. The underlying conceptual model divides the disease into two stages: pre-clinical (T0) and symptomatic (T1) breast cancer. Treating the time in these phases as a pair of dependent bivariate observations, (t0,t1), estimates are derived to describe the distribution of this random vector. To quantify the effect of screening mammography, statistical inference is made about the mammography parameters that correspond to the marginal distribution of the symptomatic phase duration (T1). This shows the hazard ratio of death from breast cancer comparing women with screen-detected tumors to those detected at their symptom onset is 0.36 (0.30, 0.42), indicating a benefit among the screen-detected cases. ^

A novel virus in swine is closely related to the human hepatitis E virus

A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine HEV is a ubiquitous agent and the majority of swine ≥3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3 were amplified by reverse transcription–PCR from sera of naturally infected pigs. The putative capsid gene (ORF2) of swine HEV shared about 79–80% sequence identity at the nucleotide level and 90–92% identity at the amino acid level with human HEV strains. The small ORF3 of swine HEV had 83–85% nucleotide sequence identity and 77–82% amino acid identity with human HEV strains. Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains. The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.

La distribution ‘juste’ de la signature savante dans les collaborations de recherche multidisciplinaire en sciences de la santé

L’auteur qui appose son nom à une publication universitaire sera reconnu pour sa contribution à la recherche et devra également en assumer la responsabilité. Il existe divers types d’agencements pouvant être utilisés afin de nommer les auteurs et souligner l’ampleur de leur contribution à ladite recherche. Par exemple, les auteurs peuvent être nommés en ordre décroissant selon l’importance de leurs contributions, ce qui permet d’allouer davantage de mérite et de responsabilité aux premiers auteurs (à l’instar des sciences de la santé) ou bien les individus peuvent être nommés en ordre alphabétique, donnant une reconnaissance égale à tous (tel qu’on le note dans certains domaines des sciences sociales). On observe aussi des pratiques émergeant de certaines disciplines ou des champs de recherche (tel que la notion d’auteur correspondant, ou directeur de recherche nommé à la fin de la liste d’auteurs). En science de la santé, lorsque la recherche est de nature multidisciplinaire, il existe différentes normes et pratiques concernant la distribution et l’ordre de la signature savante, ce qui peut donner lieu à des désaccords, voire à des conflits au sein des équipes de recherche. Même si les chercheurs s’entendent pour dire que la signature savante devrait être distribué de façon ‘juste’, il n’y a pas de consensus sur ce que l’on qualifie de ‘juste’ dans le contexte des équipes de recherche multidisciplinaire. Dans cette thèse, nous proposons un cadre éthique pour la distribution juste de la signature savante dans les équipes multidisciplinaires en sciences de la santé. Nous présentons une critique de la documentation sur la distribution de la signature savante en recherche. Nous analysons les enjeux qui peuvent entraver ou compliquer une distribution juste de la signature savante tels que les déséquilibres de pouvoir, les conflits d’intérêts et la diversité de cultures disciplinaires. Nous constatons que les normes internationales sont trop vagues; par conséquent, elles n’aident pas les chercheurs à gérer la complexité des enjeux concernant la distribution de la signature savante. Cette limitation devient particulièrement importante en santé mondiale lorsque les chercheurs provenant de pays développés collaborent avec des chercheurs provenant de pays en voie de développement. Afin de créer un cadre conceptuel flexible en mesure de s’adapter à la diversité des types de recherche multidisciplinaire, nous proposons une approche influencée par le Contractualisme de T.M. Scanlon. Cette approche utilise le respect mutuel et la force normative de la raison comme fondation, afin de justifier l’application de principes éthiques. Nous avons ainsi développé quatre principes pour la distribution juste de la signature savante en recherche: le mérite, la juste reconnaissance, la transparence et la collégialité. Enfin, nous proposons un processus qui intègre une taxonomie basée sur la contribution, afin de délimiter les rôles de chacun dans le projet de recherche. Les contributions peuvent alors être mieux comparées et évaluées pour déterminer l’ordre de la signature savante dans les équipes de recherche multidisciplinaire en science de la santé.

Urinary excretion of cadmium among Torres Strait Islanders (Australia) at risk of elevated dietary exposure through traditional foods

This study explored urinary cadmium levels among Torres Strait Islanders in response to concerns about potential health impact of high levels of cadmium in some traditional seafood (dugong and turtle liver and kidney). Cadmium levels were measured by inductively coupled mass spectrometry in de-identified urine samples collected during general screening programs in 1996 in two communities with varying dugong and turtle catch statistics. Statistical analysis was performed to identify links between cadmium levels and demographic and background health information. Geometric mean cadmium level among the sample group was 0.83 mu g/g creatinine with 12% containing over 2 mu g/g creatinine. Cadmium level was most strongly associated with age (46% of variation), followed by sex (females > males, 7%) and current smoking status (smokers > non-smokers, 4.7%). Adjusting model conditions suggested further positive associations between cadmium level and diabetes (p = 0.05) and residence in the predicted higher exposure community (p = 0.07). Positive correlations between cadmium and body fat in bivariate analysis were eliminated by control for age and sex. This study found only suggestive differences in cadmium levels between two communities with predicted variation in exposure from traditional foods. However, the data indicate that factors linked with higher cadmium accumulation overlap with those of renal disease risk (i.e. older, females, smokers, diabetes) and suggest that levels may be sufficient to contribute to renal pathology. More direct assessment of exposure and health risks of cadmium to Torres Strait Islanders is needed given the disproportionate level of diet-related disease and the cultural importance of dugong and turtle. This study highlights the need to consider social and cultural variation in exposure and to de. ne "safe'' cadmium levels during diabetes given its rising global prevalence.

Fever, methods of fever management, and caretakers' perceptions of pediatric after-hour telephone triage and advice services for children between the ages of twelve months and three years with fever

Despite the frequency with which fevers occur in children ages 1–3 years, lack of knowledge and understanding about the implications of fever and methods of fever management often results in anxiety among caretakers, sometimes prompting them to seek help at nearby emergency departments. Caretakers often look to health care professionals for advice and guidance over the telephone. The purpose of this study was to investigate caretakers' knowledge of the implications of fever, methods of fever management, perceptions of pediatric telephone triage and advice services regarding fever, and the effectiveness of after hour telephone triage directed toward improving the caretakers' ability to manage their child's fever at home. Pre-triage questionnaires were completed by 72 caretakers over the telephone before the triage encounter. Twenty-two of those same caretakers whose children were triaged using the fever guideline completed and returned the mailed post-triage questionnaire. Descriptive statistics were used to analyze responses for the larger pre-intervention group and describe comparisons for the pre and post-triage responses in the smaller sample subset (n = 22). ^