Alcohol screening and brief intervention is recommended for widespread implementation in health care systems, but it is not used routinely in most countries for a variety of reasons. Electronic screening and brief intervention (e-SBI), in which patients complete a Web-based questionnaire and are provided with personalized feedback on their drinking, is a promising alternative to practitioner delivered intervention, but its efficacy in the hospital outpatient setting has not been established.
The objective of our study was to establish the feasibility of conducting a full-scale randomized controlled trial to determine whether e-SBI reduces alcohol consumption in hospital outpatients with hazardous or harmful drinking.
The study was conducted in the outpatient department of a large public hospital in Newcastle (population 540,000), Australia. Adults with appointments at a broad range of medical and surgical outpatient clinics were invited to complete an e-SBI program on a laptop, and to report their impressions via a short questionnaire. Follow-up assessments were conducted 2-8 weeks later by email and post.
We approached 172 outpatients and 108/172 (62.8%) agreed to participate. Of the 106 patients capable of self-administering the e-SBI, 7/106 (6.6%) did not complete it (3 due to technical problems and 4 because they were called for their appointment), 15/106 (14.2%) indicated that they had not consumed any alcohol in the past 12 months, 43/106 (40.6%) screened negative for unhealthy alcohol use (scored less than 5 on the Alcohol Use Disorders Identification Test Consumption [AUDIT-C] questions), 33/106 (31.1%) screened positive for hazardous or harmful drinking (AUDIT-C score 5-9), and 8/106 (7.5%) screened positive for possible alcohol dependence (AUDIT-C score 10-12). Among the subgroup with hazardous or harmful drinking, 27/33 (82%) found the feedback on their drinking very, quite, or somewhat useful, 33/33 (100%) thought the intervention would appeal to most or some of the people who attend the service, and 22/30 (73%) completed the follow-up. We also found that some well established procedures used in trials of e-SBI in the primary care setting did not translate to the hospital outpatient setting (1) we experienced delays because the e-SBI program had to be developed and maintained by the health service’s information technology staff for security reasons, (2) recruiting patients as they left the reception desk was impractical because patients tended to arrive at the beginning of the clinics with few arrivals thereafter, and (3) use of a laptop in a fixed location resulted in some patients rushing through the e-SBI so they could return to their seat in the area they had been advised to wait in.
e-SBI is acceptable to outpatients and with some adaptation to organizational and physical conditions, it is feasible to recruit and screen patients and to deliver the intervention without disrupting normal service provision. This suggests that e-SBI could be provided routinely in this important setting if shown to be efficacious.
alcohol; drinking; screening; brief intervention; hospital; outpatients; Internet
The demographic, health and contextual factors associated with quality of life impairment are investigated in older persons from New South Wales, Australia. We examine the impact of cardiovascular and affective conditions on impairment and the potential moderating influence of comorbidity and remoteness.
Data from persons aged 55 and over were drawn from two community cohorts sampling from across urban to very remote areas. Hierarchical linear regressions were used to assess: 1) the impact of cardiovascular and affective conditions on physical and psychological quality of life impairment; and 2) any influence of remoteness on these effects (N = 4364). Remoteness was geocoded to participants at the postal code level. Secondary data sources were used to examine the social capital and health service accessibility correlates of remoteness.
Physical impairment was consistently associated with increased age, male gender, lower education, being unmarried, retirement, stroke, heart attack/angina, depression/anxiety, diabetes, hypertension, current obesity and low social support. Psychological impairment was consistently associated with lower age, being unmarried, stroke, heart attack/angina, depression/anxiety and low social support. Remoteness tended to be associated with lower psychological impairment, largely reflecting overall urban versus rural differences. The impacts of cardiovascular and affective conditions on quality of life were not influenced by remoteness. Social capital increased and health service accessibility decreased with remoteness, though no differences between outer-regional and remote/very remote areas were observed. Trends suggested that social capital was associated with lower psychological impairment and that the influence of cardiovascular conditions and social capital on psychological impairment was greater for persons with a history of affective conditions. The beneficial impact of social capital in reducing psychological impairment was more marked for those experiencing financial difficulty.
Cardiovascular and affective conditions are key determinants of physical and psychological impairment. Persons affected by physical-psychological comorbidity experience greater psychological impairment. Social capital is associated with community remoteness and may ameliorate the psychological impairment associated with affective disorders and financial difficulties. The use of classifications of remoteness that are sensitive to social and health service accessibility determinants of health may better inform future investigations into the impact of context on quality of life outcomes.
Cardiovascular disease; Urban–rural; Social capital; Quality of life; Physical and psychological health; Over 55 years
Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts’ opinions and empirical evidence to estimate the relative importance of 15 types of information at the single nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from ten experts using a two-round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta-analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta-analysis or more than one study as conferring the highest relative probability of true association, while previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, while location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research.
Gene prioritization; Genome-wide association studies; Bioinformatics databases
Prioritization is the process whereby a set of possible candidate genes or SNPs is ranked so that the most promising can be taken forward into further studies. In a genome-wide association study, prioritization is usually based on the p-values alone, but researchers sometimes take account of external annotation information about the SNPs such as whether the SNP lies close to a good candidate gene. Using external information in this way is inherently subjective and is often not formalized, making the analysis difficult to reproduce. Building on previous work that has identified fourteen important types of external information, we present an approximate Bayesian analysis that produces an estimate of the probability of association. The calculation combines four sources of information: the genome-wide data, SNP information derived from bioinformatics databases, empirical SNP weights, and the researchers’ subjective prior opinions. The calculation is fast enough that it can be applied to millions of SNPS and although it does rely on subjective judgments, those judgments are made explicit so that the final SNP selection can be reproduced. We show that the resulting probability of association is intuitively more appealing than the p-value because it is easier to interpret and it makes allowance for the power of the study. We illustrate the use of the probability of association for SNP prioritization by applying it to a meta-analysis of kidney function genome-wide association studies and demonstrate that SNP selection performs better using the probability of association compared with p-values alone.
replication; prior knowledge; genome-wide studies
Objective. To conduct a systematic review and meta-analysis of hemoglobin effect on the pregnancy outcomes. Methods. We searched MEDLINE and SCOPUS from January 1, 1990 to April 10, 2011. Observational studies addressing association between hemoglobin and adverse pregnancy outcomes were selected. Two reviewers independently extracted data. A mixed logistic regression was applied to assess the effects of hemoglobin on preterm birth, low birth weight, and small for gestational age. Results. Seventeen studies were included in poolings. Hemoglobin below 11 g/dL was, respectively, 1.10 (95% CI: 1.02–1.19), 1.17 (95% CI: 1.03–1.32), and 1.14 (95% CI: 1.05–1.24) times higher risk of preterm birth, low birth weight, and small for gestational age than normal hemoglobin in the first trimester. In the third trimester, hemoglobin below 11 g/dL was 1.30 (95% CI: 1.08–1.58) times higher risk of low birth weight. Hemoglobin above 14 g/dL in third trimester decreased the risk of preterm term with ORs of 0.50 (95% CI: 0.26–0.97), but it might be affected by publication bias. Conclusions. Our review suggests that hemoglobin below 11 g/dl increases the risk of preterm birth, low birth weight, and small gestational age in the first trimester and the risk of low birth weight in the third trimester.
Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10−8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10−12 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.
This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.
Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.
Measurements and Main Results
In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.
After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function.
To determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters.
This cross-sectional study was conducted between March and December 2009. Any patient aged ≥30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate.
A total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI.
Participants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes.
Background and Purpose
Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS.
Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model.
Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons.
Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.
cerebral infarct; genetics; ischemia
Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome (LS) is a cancer syndrome characterised by early-onset epithelial cancers, especially colorectal cancer (CRC) and endometrial cancer. The aim of the current study was to use SNP-array technology to identify genomic aberrations which could contribute to the increased risk of cancer in HNPCC/LS patients.
Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation (CNV) calling and association analyses were performed using Nexus software, with significant results validated using QuantiSNP. TaqMan Copy-Number assays were used for verification of CNVs showing significant association with HNPCC/LS identified by both software programs.
We detected copy number (CN) gains associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls, Nexus; p = 3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p = 5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for validation of CNVs showing significant association with HNPCC/LS. In addition, CNV burden (total CNV length, average CNV length and number of observed CNV events) was significantly greater in cases compared to controls.
A greater CNV burden was identified in HNPCC/LS cases compared to controls supporting the notion of higher genomic instability in these patients. One intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and deserves further investigation. The results from this study highlight the complexities of fluorescent based CNV analyses. The inefficiency of both CNV detection methods to reproducibly detect observed CNVs demonstrates the need for sequence data to be considered alongside intensity data to avoid false positive results.
HNPCC; Lynch syndrome; SNP arrays; CNVs; CNV burden
Participation rates in colorectal cancer screening (CRC) are low. Relatively little is known about screening uptake across varying levels of risk and across population groups. The purpose of the current study was to identify factors associated with (i) ever receiving colorectal cancer (CRC) testing; (ii) risk-appropriate CRC screening in accordance with guidelines; and (iii) recent colonoscopy screening.
1592 at-risk persons (aged 56–88 years) were randomly selected from the Hunter Community Study (HCS), Australia. Participants self-reported family history of CRC was used to quantify risk in accordance with national screening guidelines.
1117 participants returned a questionnaire; 760 respondents were eligible for screening and analysis. Ever receiving CRC testing was significantly more likely for persons: aged 65–74 years; who had discussed with a doctor their family history of CRC or had ever received screening advice. For respondents “at or slightly above average risk”, guideline-appropriate screening was significantly more likely for persons: aged 65–74 years; with higher household income; and who had ever received screening advice. For respondents at “moderately or potentially high risk”, guideline-appropriate screening was significantly more likely for persons: with private health insurance and who had discussed their family history of CRC with a doctor. Colonoscopy screening was significantly more likely for persons: who had ever smoked; discussed their family history of CRC with a doctor; or had ever received screening advice.
The level of risk-appropriate screening varied across populations groups. Interventions that target population groups less likely to engage in CRC screening are pivotal for decreasing screening inequalities.
A reliable and accurate estimation of liver size by physical examination is an important aspect of the clinical assessment of a patient. The scratch test uses auscultation to detect the lower liver edge by using the difference in sound transmission through the abdominal cavity over solid and hollow organs. The test is thought to be particularly useful if the abdomen is tense, distended, obese, or very tender. Although the sign is often taught to medical students and residents, the value of the technique for detecting the liver edge has become controversial.
The study was performed in two parts. In the first part, 18 patients undergoing upper abdominal ultrasound as outpatients were randomly selected and the scratch test was performed by two raters independently, followed by ultrasound (USG) as the reference standard. In the second part of the study, the two raters independently performed the scratch test on separate randomly selected patients (15 patients by rater 1, and 16 patients by rater 2), followed by USG.
Agreement between raters on the scratch test was very high, with an intra-class correlation coefficient of 0.97. The agreement between the raters and the USG was 0.37 using Spearman’s rho. A Bland –Altman plot indicated that, on average, raters underestimated the distance from the right costal margin to the liver edge by only about 2.4 centimeters compared to USG. This translates into 37% and 54% of raters’ estimates falling within 2 and 3 cm of USG estimates. Each unit increase in BMI increased the discrepancy between raters and USG by 0.26 cm (p = 0.012).
The scratch test has very high reproducibility and overall agreement between the scratch test and USG was moderate, with a spearman’s rho of 0.37. The accuracy may potentially be improved by using the point of initial sound transmission rather than the point of maximal transmission. We conclude that the scratch test deserves further investigation.
Scratch test; Hepatomegaly; Auscultation; Liver edge; Liver span
Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.
A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.
No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, −1.3±0.23 (beta ± standard error), p = 6.6×10−9. Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r2 ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.
This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.
The role of small solute clearance on mortalities in patients with CAPD has been controversial. We therefore conducted a study with 3 years' follow up in adult patients who participated in the CAPD-first policy.
There were 11,523 patients with end-stage renal disease who participated in the CAPD-first policy between 2008 and 2011. Among them, 1,177 patients were included in the retrospective cohort study. A receiver operating characteristic curve was applied to calibrate the cutoffs of tKt/V, rKt/V and tCrcl. Kaplan-Meier and Cox-regression models with time varying covariates were applied to estimate overall death rate, probability of death and prognosis, respectively.
The cutoffs of rKt/V and tKt/V were 0.25 and 1.75, respectively. The Cox regression suggested that the higher these clearance parameters, the lower the risks of death after adjusting for covariables. The risks of death for those above these cutoffs were 57% (HR = 0.43, 95% CI: 0.31, 0.60) and 29% (HR = 0.71, 95% CI: 0.52, 0.98) lower for rKt/V and tKt/V, respectively. Age, serum albumin, hemoglobin, systolic blood pressure, and ultra-filtration volume significantly affected the mortality outcome.
Our study suggested that the cutoffs of 0.25 and 1.75 for rKt/V and tKt/V might be associated with mortality in CAPD patients. A minimum tKt/V of 1.75 should be targeted, but increased dialysis dosage to achieve tKt/V > 2.19 adds no further benefit. Serum albumin, hemoglobin, SBP, and UF volume are also associated with mortality. However, our study may face with selection and other unobserved confounders, so further randomized controlled trials are required to confirm these cutoffs.
Adequacy indices; CAPD; Continuous ambulatory peritoneal dialysis; Mortality; Peritoneal small solute clearance; Prognostic factors
Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.
Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60–70) years].
Regression analysis showed that: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P<0.001), cysteine (P = 0.007), and glutamylcysteine (P<0.001) were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.
After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA) and/or cationic amino acid transport requires further investigations.
Electronic screening and brief intervention (e-SBI) is a promising alternative to screening and brief intervention by health-care providers, but its efficacy in the hospital outpatient setting, which serves a large proportion of the population, has not been established. The aim of this study is to estimate the effect of e-SBI in hospital outpatients with hazardous or harmful drinking.
This randomized controlled trial will be conducted in the outpatient department of a large tertiary referral hospital in Newcastle (population 540,000), Australia. Some 772 adults with appointments at a broad range of medical and surgical outpatient clinics who score 5–9 inclusive on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) subscale will be randomly assigned in a 1:1 ratio to electronic alcohol screening alone (control) or to e-SBI. As randomization will be effected by computer, researchers and participants (who will be invited to participate in a study of alcohol use over time) will be blinded to group assignment. The primary analysis will be based on the intention-to-treat principle and compare weekly volume (grams of alcohol) and the full AUDIT score with a six-month reference period between the groups six months post randomization. Secondary outcomes, assessed six and 12 months after randomization, will include drinking frequency, typical occasion quantity, proportion who report binge drinking, proportion who report heavy drinking, and health-care utilization.
If e-SBI is efficacious in outpatient settings, it offers the prospect of systematically and sustainably reaching a large number of hazardous and harmful drinkers, many of whom do not otherwise seek or receive help.
Australian New Zealand Clinical Trials Registry ACTRN12612000905864.
Alcohol; Screening; Brief intervention; Internet; Intervention; Clinical trials; Hospital outpatients
We conducted a genome-wide association (GWA) meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese1 and European2 ancestry. We show that rs12700667 on chromosome 7p15.2, previously found in Europeans, replicates in Japanese (P = 3.6 × 10−3), and confirm association of rs7521902 on 1p36.12 near WNT4. In addition, we establish association of rs13394619 in GREB1 on 2p25.1 and identify a novel locus on 12q22 near VEZT (rs10859871). Excluding European cases with minimal or unknown severity, we identified additional novel loci on 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and produced P < 5 × 10−8 in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the European and Japanese GWA cohorts (P = 8.8 × 10−11), indicating that many weakly associated SNPs represent true endometriosis risk loci and risk prediction and future targeted disease therapy may be transferred across these populations.
Chronic arsenic exposure and its association with hypertension in adults are inconclusive and this cross-sectional study investigated the association. The study was conducted between January and July 2009 among 1,004 participants from 1,682 eligible women and men aged ≥30 years living in rural Bangladesh who had continuously consumed arsenic-contaminated drinking water for at least 6 months. Hypertension was defined as systolic blood pressure ≥140 mmHg (systolic hypertension) and diastolic blood pressure ≥90 mmHg (diastolic hypertension). Pulse pressure was calculated by deducting diastolic from systolic pressure and considered to be increased when the difference was ≥55 mmHg. The prevalence of hypertension was 6.6% (95% CI: 5.1–8.3%). After adjustment for other factors, no excess risk of hypertension was observed for arsenic exposure >50μg/L or to that of arsenic exposure as quartiles or as duration. Arsenic concentration as quartiles and >50 μg/L did show a strong relationship with increased pulse pressure (adjusted OR: 3.54, 95% CI: 1.46–8.57), as did arsenic exposure for ≥10 years (adjusted OR: 5.25, 95% CI: 1.41–19.51). Arsenic as quartiles showed a dose response relationship with increased pulse pressure. Our study suggests an association between higher drinking water arsenic or duration and pulse pressure, but not hypertension.
arsenic; drinking-water; hypertension; pulse-pressure; Bangladesh
The variation of determinants of mental health with remoteness has rarely been directly examined. The current research aims to examine whether the association of psychosocial factors with psychological distress outcomes varies with increasing remoteness.
Participants were persons aged 55 and over from two community cohorts sampling from across rural and urban New South Wales (N = 4219; mean age = 69.00 years; 46.1% male). Measures of social support from these studies were calibrated to facilitate comparison across the sample. Remoteness was assessed using a continuous measure, the Accessibility/Remoteness Index of Australia. The association between demographic characteristics, social support, remoteness, and their interactions with remoteness in the prediction of high psychological distress (cut-off > 21 on the Kessler 10) were examined using logistic regression.
Not being in a married or defacto relationship (OR 0.69; 99% CI 0.51-0.94), lower education (OR 0.52; 99% CI 0.38-0.71) and decreased social support (OR 0.36; 99% CI 0.31-0.42) significantly predicted psychological distress. There was a significant interaction of age and remoteness (OR 0.84; 99% CI 0.67-1.00), indicating that as remoteness increases, older persons are less likely to be highly distressed, as well as a significant interaction of social support and remoteness (OR 1.22; 99% CI 1.04-1.44), indicating that as remoteness decreases, persons with low levels of social support are more likely to be highly distressed.
Remoteness may moderate the influence of social support and age on psychological distress outcomes.
Rural health; Psychological distress; Social support; Aged 55 and over
Craniocervical arterial dissection is a major cause of ischaemic stroke in young adults. The pathogenesis is not fully understood but is thought to be related to a combination of an intrinsic weakness in the arterial wall and an external trigger. Intrinsic susceptibility is thought to be a generalised arteriopathy, vascular anomaly or genetic predisposition. Proposed extrinsic factors include recent viral infection and minor mechanical trauma to the neck, including neck manipulation, which has raised concerns amongst manual practitioners in particular as to the appropriate screening of patients and avoidance of more vigorous therapeutic techniques. The presenting features of dissection may mimic a musculoskeletal presentation, creating a diagnostic dilemma for primary care practitioners. Early recognition is critical so that appropriate management can be commenced.
The aims of this study are to prospectively investigate young patients ≤55 years admitted to hospital with radiologically diagnosed craniocervical arterial dissection compared to matched controls with stroke but not dissection, to identify risk factors and early presenting clinical features, so these may be more readily identified by primary care practitioners.
Patients ≤ 55 years presenting to hospital with craniocervical arterial dissection and controls will have their medical records reviewed and be interviewed and questioned about possible risk factors, preceding events to admission such as recent neck trauma, and presenting clinical features including any preceding transient ischaemic features. Clinical assessment will include a connective tissue screening examination to identify subclinical connective tissue disorders. Radiology and blood screening will be reviewed for typical features and inflammatory markers. Functional outcome will be reviewed to determine the burden of the stroke.
This study will provide descriptive and comparative data on intrinsic and extrinsic risk factors for craniocervical arterial dissection and outline the typical clinical presentation, including the nature of early presenting features which might assist practitioners to identify those patients for whom vigorous manual therapy of the neck is inappropriate and alert them to those for whom immediate urgent medical care should be sought.
Rural populations experience a higher suicide rate than urban areas despite their comparable prevalence of depression. This suggests the identification of additional contributors is necessary to improve our understanding of suicide risk in rural regions. Investigating the independent contribution of depression, and the impact of co-existing psychiatric disorders, to suicidal ideation and suicide attempts in a rural community sample may provide clarification of the role of depression in rural suicidality.
618 participants in the Australian Rural Mental Health Study completed the Composite International Diagnostic Interview, providing assessment of lifetime suicidal ideation and attempts, affective disorders, anxiety disorders and substance-use disorders. Logistic regression analyses explored the independent contribution of depression and additional diagnoses to suicidality. A receiver operating characteristic (ROC) analysis was performed to illustrate the benefit of assessing secondary psychiatric diagnoses when determining suicide risk.
Diagnostic criteria for lifetime depressive disorder were met by 28% (174) of the sample; 25% (154) had a history of suicidal ideation. Overall, 41% (63) of participants with lifetime suicidal ideation and 34% (16) of participants with a lifetime suicide attempt had no history of depression. When lifetime depression was controlled for, suicidal ideation was predicted by younger age, being currently unmarried, and lifetime anxiety or post-traumatic stress disorder. In addition to depression, suicide attempts were predicted by lifetime anxiety and drug use disorders, as well as younger age; being currently married and employed were significant protective factors. The presence of comorbid depression and PTSD significantly increased the odds of reporting a suicide attempt above either of these conditions independently.
While depression contributes significantly to suicidal ideation, and is a key risk factor for suicide attempts, other clinical and demographic factors played an important role in this rural sample. Consideration of the contribution of factors such as substance use and anxiety disorders to suicidal ideation and behaviours may improve our ability to identify individuals at risk of suicide. Acknowledging the contribution of these factors to rural suicide may also result in more effective approaches for the identification and treatment of at-risk individuals.
Little data exists on the factors associated with health care seeking behaviour for primary symptoms of colorectal cancer (CRC). This study aimed to identify individual, provider and psychosocial factors associated with (i) ever seeking medical advice and (ii) seeking early medical advice for primary symptoms of colorectal cancer (CRC).
1592 persons aged 56–88 years randomly selected from the Hunter Community Study (HCS) were sent a questionnaire.
Males and those who had received screening advice from a doctor were at significantly higher odds of ever seeking medical advice for rectal bleeding. Persons who had private health coverage, consulted a doctor because the ‘symptom was serious’, or who did not wait to consult a doctor for another reason were at significantly higher odds of seeking early medical advice (< 2 weeks). For change in bowel habit, persons with lower income, within the healthy weight range, or who had discussed their family history of CRC irrespective of whether informed of ‘increased risk’ were at significantly higher odds of ever seeking medical advice. Persons frequenting their GP less often and seeing their doctor because the symptom persisted were at significantly higher odds of seeking early medical advice (< 2 weeks).
The seriousness of symptoms, importance of early detection, and prompt consultation must be articulated in health messages to at-risk persons. This study identified modifiable factors, both individual and provider-related to consultation behaviour. Effective health promotion efforts must heed these factors and target sub-groups less likely to seek early medical advice.
Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works.
This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D.
A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose–response pattern was also observed.
These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.
The burden of patients with heart failure on health care systems is widely recognised, although there have been few attempts to quantify individual patterns of care and differences in health service utilisation related to age, socio-economic factors and the presence of co-morbidities. The aim of this study was to assess the typical profile, trajectory and resource use of a cohort of Australian patients with heart failure using linked population-based, patient-level data.
Using hospital separations (Admitted Patient Data Collection) with death registrations (Registry of Births, Deaths and Marriages) for the period 2000–2007 we estimated age- and gender-specific rates of index admissions and readmissions, risk factors for hospital readmission, mean length of stay (LOS), median survival and bed-days occupied by patients with heart failure in New South Wales, Australia.
We identified 29,161 index admissions for heart failure. Admission rates increased with age, and were higher for males than females for all age groups. Age-standardised rates decreased over time (256.7 to 237.7/100,000 for males and 235.3 to 217.1/100,000 for females from 2002–3 to 2006–7; p = 0.0073 adjusted for gender). Readmission rates (any cause) were 27% and 73% at 28-days and one year respectively; readmission rates for heart failure were 11% and 32% respectively. All cause mortality was 10% and 28% at 28 days and one year. Increasing age was associated with more heart failure readmissions, longer LOS and shorter median survival. Increasing age, increasing Charlson comorbidity score and male gender were risk factors for hospital readmission. Cohort members occupied 954,888 hospital bed-days during the study period (any cause); 383,646 bed-days were attributed to heart failure admissions.
The rates of index admissions for heart failure decreased significantly in both males and females over the study period. However, the impact on acute care hospital beds was substantial, with heart failure patients occupying almost 200,000 bed-days per year in NSW over the five year study period. The strong age-related trends highlight the importance of stabilising elderly patients before discharge and community-based outreach programs to better manage heart failure and reduce readmissions.
Heart failure; Hospitalization; Health services research; Australia