131 resultados para Millennium Cohort Study
Resumo:
Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians.
Results: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03).
Conclusion: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.
Resumo:
Objective: To examine the association of adolescent depression and anxiety symptoms with alcohol abuse or dependence in young adulthood.
Design, setting and participants: Cohort study of the health and wellbeing of adolescents and young adults in Victoria, assessed at 8 waves (periods) of data collection, from age 14 to 24 years, between 1992 and 2003. Young people who participated in the cohort study at least once during the six adolescent assessment points (conducted 6 months apart, from age 14 to 17 years), at least once during young adulthood and who were alive at Wave 8 (n = 1758).
Main outcome measure: Alcohol abuse or dependence assessed using the alcohol and substance abuse modules of the Composite International Diagnostic Interview at age 24 years.
Results: Adolescents with moderate to high levels of depression and anxiety symptoms (measured by the revised Clinical Interview Schedule) had an increased risk of alcohol abuse or dependence in young adulthood, compared with young adults with low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Risk was higher for those with symptoms at more than two adolescent assessment points (odds ratio [OR] 1.9; 95% CI, 1.7–2.0) and for those with symptoms at one or two assessment points (OR 1.3; 95% CI, 1.2–1.4), compared with those with no above-threshold symptoms in adolescence.
Conclusions: Adolescents with depression and anxiety symptoms are at increased risk for alcohol use disorders into young adulthood. They warrant vigilance from primary care providers in relation to alcohol use well into adulthood.
Resumo:
Study Objective: To examine relationships between depressive symptoms in adolescence (14-18 years of age) and becoming pregnant, completing a pregnancy (live birth) and terminating a pregnancy in young adulthood (21-24 years of age).
Participants and Design: Data from 1000 females were drawn from a larger sample of 1943 young Australians participating in a longitudinal study of adolescent health and development, followed across 8 waves from adolescence (waves 1-6) to young adulthood (waves 7 and 8).
Setting: Victoria, Australia.
Main Outcome Measures: Pregnancy, pregnancy completion and pregnancy termination between 21-24 years of age.
Results: We observed a twofold increase in the odds of becoming pregnant in those reporting persisting patterns of depressive symptoms during adolescence (2þ waves); however, after staged adjustment for adolescent antisocial behaviour, drug use and socioeconomic disadvantage, there was no evidence of association. Of particular note, and consistent with previous research, adolescent antisocial and drug use behavior were strongly associated with becoming pregnant and pregnancy termination in young adulthood.
Conclusions: Adolescent antisocial and drug use behavior, not depressive symptoms, independently predict pregnancy outcomes in young adulthood.
Resumo:
We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val158Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose–response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met158 [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76–0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79–0.99, P = 0.033). There was no evidence for a dose–response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29–0.70, P < 0.001) among carriers homozygous for both the COMT Met158 and the 5HTTLPR Short alleles (Met158Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.
Overweight and obesity between adolescence and young adulthood : a ten-year prospective cohort study
Resumo:
Objective: To examine the relationship between childhood sexual abuse (CSA) before the age of 16 years and later onset of bulimia and anorexia nervosa symptoms in females.
Design: A longitudinal cohort study of adolescents observed from August 1992 to March 2003. The cohort was defined in a 2-stage cluster sample using 44 Australian schools in Victoria.
Setting: Population based.
Participants: A total of 1936 persons participated at least once and survived to the age of 24 years, including 999 females. The mean (SD) age of females at the start of follow- up was 14.91 (0.39) years; and at completion, 24.03 (0.55) years.
Main Exposure: Self-reported CSA before the age of 16 years was ascertained retrospectively at the age of 24 years.
Outcome Measures: Incident Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)–defined partial syndromes of anorexia and bulimia nervosa were identified between waves 4 (mean age, 16.3 years) and 6 (mean age, 17.4 years) using the Branched Eating Disorder Test.
Results: The incidence of bulimic syndrome during adolescence was 2.5 (95% confidence interval, 0.80-8.0) times higher among those who reported 1 episode of CSA and 4.9 (95% confidence interval, 1.9-12.7) times higher among those who reported 2 or more episodes of CSA, compared with females reporting no episodes, adjusted for age and background factors. The association persisted after adjusting for possible confounders or mediators measured 6 months earlier, including psychiatric morbidity and dieting behavior. There was little evidence of an association between CSA and partial syndromes of incident anorexia nervosa.
Conclusion: Childhood sexual abuse seems to be a risk factor for the development of bulimic syndromes, not necessarily mediated by psychiatric morbidity or severe dieting.
Resumo:
Introduction : Although obesity is a modifiable risk factor for knee osteoarthritis (OA), the effect of weight gain on knee structure in young and healthy adults has not been examined. The aim of this study was to examine the relationship between body mass index (BMI), and change in BMI over the preceding 10-year period, and knee structure (cartilage defects, cartilage volume and bone marrow lesions (BMLs)) in a population-based sample of young to middle-aged females.
Methods : One hundred and forty-two healthy, asymptomatic females (range 30 to 49 years) in the Barwon region of Australia, underwent magnetic resonance imaging (MRI) during 2006 to 2008. BMI measured 10 years prior (1994 to 1997), current BMI and change in BMI (accounting for baseline BMI) over this period, was assessed for an association with cartilage defects and volume, and BMLs.
Results : After adjusting for age and tibial plateau area, the risk of BMLs was associated with every increase in one-unit of baseline BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.009), current BMI (OR 1.13 (95% CI 1.04 to 1.23) P = 0.005), and per one unit increase in BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.01). There was a trend for a one-unit increase in current BMI to be associated with increased risk of cartilage defects (OR 1.06 (95% CI 1.00 to 1.13) P = 0.05), and a suggestion that a one-unit increase in BMI over 10 years may be associated with reduced cartilage volume (-17.8 ml (95% CI -39.4 to 3.9] P = 0.10). Results remained similar after excluding those with osteophytes.
Conclusions : This study provides longitudinal evidence for the importance of avoiding weight gain in women during early to middle adulthood as this is associated with increased risk of BMLs, and trend toward increased tibiofemoral cartilage defects. These changes have been shown to precede increased cartilage loss. Longitudinal studies will show whether avoiding weight gain in early adulthood may play an important role in diminishing the risk of knee OA.
Resumo:
Lower socioeconomic status (SES) is associated with a higher prevalence of major risk factors for cardiovascular disease (CVD). However, few longitudinal studies have examined the association between SES and CVD risk factors over time. We aimed to determine whether SES, using education as a proxy, is associated with the onset of CVD risk factors over 5 years in an Australian adult cohort study.
Participants in the Australian Diabetes, Obesity and Lifestyle study (AusDiab) study aged 25 years and over who attended both baseline and 5-year follow-up examinations (n=5 967) were categorised according to educational attainment. Cardiovascular risk factor data at both time points were ascertained through questionnaire and physical measurement.
Women with lower education had a greater risk of progressing from normal weight to overweight or obesity than those with higher education (age-adjusted OR 1.57, 95% CI 1.06-2.31). Both men and women with lower education were more likely to develop diabetes (age-adjusted OR from higher education 1.75, 95% CI 1.14-2.71 and 3.01, 95% CI 1.26-7.20, respectively). A lower level of education was associated with a greater number of risk factors accumulated over time in women (OR of progressing from having two or less risk factors at baseline to three or more at follow up, 2.04, 95% 1.32-3.14).
In this Australian population-based study, lower educational attainment was associated with an increased risk of developing both individual and total CVD risk factors over a 5-year period. These findings suggest that SES inequalities in CVD will persist into the future.
Resumo:
Background Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables.
Methods A sample of 2000 participants from a cohort study (n = 41 514) was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare) number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review.
Results Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%.
Conclusions High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables.
Resumo:
Summary Despite targeted attempts to reduce post-fracture care gaps, we hypothesized that a larger care gap would be experienced by First Nations compared to non-First Nations people. First Nations peoples were eight times less likely to receive post-fracture care compared to non-First Nations peoples, representing a clinically significant ethnic difference in post-fracture care.
Introduction First Nations peoples are the largest group of aboriginal (indigenous or native) peoples in Canada. Canadian First Nations peoples have a greater risk of fracture compared to non-First Nations peoples. We hypothesized that ethnicity might be associated with a larger gap in post-fracture care.
Methods Non-traumatic major osteoporotic fractures for First Nations and non-First Nations peoples aged ≥50 years were identified from a population-based data repository for Manitoba, Canada between April 1996 and March 2002. Logistic regression analysis was used to examine the probability of receiving a BMD test, a diagnosis of osteoporosis, or beginning an osteoporosis-related drug in the 6 months post-fracture.
Results A total of 11,234 major osteoporotic fractures were identified; 502 occurred in First Nations peoples. After adjustment for confounding covariates, First Nations peoples were less likely to receive a BMD test [odds ratio (OR) 0.1, 95% confidence interval (CI), 0.0–0.5], osteoporosis-related drug treatment (OR, 0.5; 95% CI, 0.3–0.7), or a diagnosis of osteoporosis (OR, 0.5; 95% CI, 0.3–0.7) following a fracture compared to non-First Nations peoples. Females were more likely to have a BMD test (OR, 5.0; 95% CI, 2.6–9.3), to be diagnosed with osteoporosis (OR, 1.7; 95% CI, 1.5–2.0), and to begin drug treatment (OR, 4.1; 95% CI, 2.7–6.4) compared to males.
Conclusions An ethnicity difference in post-fracture care was observed. Further work is needed to elucidate underlying mechanisms for this difference and to determine whether failure to initiate treatment originates with the medical practitioner, the patient, or a combination of both. It is imperative that all residents of Manitoba receive efficacious and equal care post-fracture, regardless of ethnicity.
Resumo:
Background: The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of
fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia.
Methodology/Principal Findings: Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was
62 years (range 3–94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic
regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p,0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27–2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases.
Conclusions: Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.
