Lithium use and bone health in women with bipolar disorder: A cross-sectional study.

INTRODUCTION: Several psychiatric disorders and medications used to treat them appear to be independently associated with skeletal deficits. As there is increasing evidence that lithium possesses skeletal protective properties, we aimed to investigate the association between lithium use and bone health in a group of women with bipolar disorder. METHOD: Women with bipolar disorder (n = 117, 20+ years) were recruited from south-eastern Australia. Bipolar disorder was confirmed using a clinical interview (SCID-I/NP). Bone mineral density (BMD; g/cm2 ) was measured at the spine, hip and total body using dual-energy x-ray absorptiometry and low bone mass determined by BMD T-score of <-1.0. Weight and height were measured, socioeconomic status (SES) determined and information on medication use and lifestyle factors self-reported. Linear and logistic regression were used to test associations between lithium and (i) BMD and (ii) low bone mass, respectively. RESULTS: Thirty-five (29.9%) women reported current lithium use. Lithium users and non-users differed in regard to SES and BMD; otherwise, groups were similar. After adjustments, mean BMD among lithium users was 5.1% greater at the spine (1.275 [95% CI 1.229-1.321] vs. 1.214 [1.183-1.244] g/cm2 , p = 0.03), 4.2% greater at the total hip (0.979 [0.942-1.016] vs. 0.938 [0.910-0.966] g/cm2 , p = 0.03) and 2.2% greater at the total body (1.176 [1.148-1.205] vs. 1.150 [1.129-1.171] g/cm2 , p = 0.08) compared to participants not receiving lithium. Lithium users were also less likely to have low bone mass (22.9% vs. 43.9%, p = 0.031). Associations persisted after adjustment for confounders. CONCLUSION: These data suggest lithium is associated with greater BMD and reduced risk of low bone mass in women with bipolar disorder. Research into the underlying mechanisms is warranted.

Long-Term Implications of Socioeconomic Status on Major Adverse Cardiovascular, Cerebrovascular Events (MACCE), and All-Cause Mortality.

BACKGROUND: Socio-economic status (SES) has a large impact on health through a complex interplay of upstream, midstream and downstream factors. However, little is known about the predictive role of SES on long-term major adverse cardiovascular, cerebrovascular events, and mortality (MACCE). AIM: To determine the long-term relationship between SES and MACCE for men and women. The secondary endpoint was to determine the relationship between SES and all-cause mortality. METHOD: A total of 3,034 participants (1,494 women and 1,540 men) were assessed at baseline in the Geelong Osteoporosis Study, a large regional Australian population cohort study. Area-based SES was assessed, utilising the Index of Relative Socio-Economic Disadvantage (IRSD) and grouped into quintiles. The primary endpoint, MACCE, was defined as a composite of myocardial infarction, heart failure hospitalisation, malignant arrhythmias, stroke, and all-cause mortality. The secondary endpoint was all-cause mortality. Baseline data including age, sex, smoking status and alcohol use, and comorbidities were collected between 1993-1997 for women, and 2001-2006 for men, with follow-up over 30 and 22 years, respectively. Logistic regression was utilised to assess MACCE and all-cause mortality outcomes across the SES quintiles. RESULTS: Participants lost to follow-up or with incomplete data collection were excluded leaving 2,173 participants eligible for analysis. SES was associated with MACCE outcomes. Compared with Quintile I (lowest SES stratum), the odds of MACCE for each IRSD stratum were: Quintile II, odds ratio (OR) 0.85 (95% confidence interval [CI] 0.65-1.13); Quintile III, OR 0.69 (95% CI 0.51-0.91); Quintile IV, OR 0.66 (95% CI 0.50-0.88); and, Quintile V, OR 0.55 (95% CI 0.41-0.72). In the adjusted model, an inverse trend was noted, with reducing MACCE outcomes with an increasing SES status; IRSD Quintile II, OR 0.85 (95% CI 0.62-1.17); Quintile III, OR 0.70 (95% CI 0.50-0.97); Quintile IV, OR 0.73 (95% CI 0.52-1.02); and, Quintile V, OR 0.54 (95% CI 0.39-0.74). SES was inversely associated with all-cause mortality; IRSD Quintile II (OR 0.87, 95% CI 0.66-1.16) failed to achieve significance however IRSD Quintile III (OR 0.65, 95% CI 0.48-0.88), Quintile IV (OR 0.59, 95% CI 0.44-0.80) and Quintile V (OR 0.46, 95% CI 0.34-0.62) had a lower risk of mortality compared with Quintile I. In the adjusted model, an inversely proportional trend was noted between SES and all-cause mortality; IRSD Quintile II (OR 0.82, 95% CI 0.59-1.15), IRSD Quintile III (OR 0.63, 95% CI 0.49-0.95), Quintile IV (OR 0.59, 95% CI 0.45-0.90) and Quintile V (OR 0.44, 95% CI 0.31-0.61) had fewer mortality events compared with IRSD Quintile I. CONCLUSIONS: Our research indicates that being part of a lower socio-economic stratum is linked to a higher likelihood of experiencing negative cardiovascular and cerebrovascular events, along with an increased risk of overall mortality. SES is an important risk stratification marker for long-term prognosis of cardiovascular diseases and stroke, and warrants further investigation.

Anxiety disorders are associated with reduced bone mineral density in men: Findings from the Geelong Osteoporosis Study.

OBJECTIVE: Certain psychiatric disorders, including depression, appear to impact adversely on bone health. Anxiety disorders are highly prevalent but few studies have examined their effects on bone tissue. This study investigated the effect of anxiety disorders on bone mineral density (BMD). METHODS: This prospective cohort study used data from the Geelong Osteoporosis Study. Participants were women and men aged ≥20 years randomly selected from the electoral roll and followed up for a mean of 14.7 and 11.0 years, respectively. Participants were assessed for a lifetime history of an anxiety disorder using the Structured Clinical Interview for DSM-IV-TR. BMD in the lumbar spine and femoral neck was measured using dual-energy x-ray absorptiometry. RESULTS: Eight hundred and ninety women and 785 men participated in the study. Adjusting for sociodemographic, biometric and lifestyle factors, medical comorbidities and medication use, anxiety disorders were associated with reduced BMD at the lumbar spine (partial η2 = 0.006; p = 0.018) and femoral neck (partial η2 = 0.006; p = 0.003) in men. These associations became non-significant when men with a history of comorbid mood disorders were excluded from the analysis. There was no significant association between anxiety disorders and BMD in women (p ≥ 0.168). CONCLUSIONS: Anxiety disorders are associated with reduced BMD in men. This effect may be mediated by comorbid depression.

Metformin is Protective Against the Development of Mood Disorders.

INTRODUCTION: Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders. METHODS: This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders. RESULTS: The transcriptional effects of a combination of drugs commonly used to treat mood disorders included regulation of the steroid and terpenoid backbone biosynthesis pathways, suggesting a mechanism involving cholesterol biosynthesis, and effects on the thyroid hormone signaling pathway. Connectivity Map analysis highlighted metformin, an FDA-approved treatment for type 2 diabetes, as a drug having global transcriptional effects similar to the mood disorder drug combination investigated. In a retrospective cohort study, we found evidence that metformin is protective against the onset of mood disorders. DISCUSSION: These results provide proof-of-principle of combining gene expression signature technology with pharmacoepidemiology to identify potential novel drugs for treating mood disorders. Importantly, metformin may have utility in the treatment of mood disorders, warranting future randomized controlled trials to test its efficacy.

Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative.

OBJECTIVES: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. METHODS: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. RESULTS: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. CONCLUSIONS: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

Falls in community-dwelling women with bipolar disorder: a case-control study.

BACKGROUND: Falls are a common occurrence in psychiatric hospital settings, however population-based research among individuals with psychiatric disorders, in particular bipolar disorder (BD) is scant. Thus, we aimed to investigate falls risk in community-dwelling women diagnosed with BD. METHODS: Women with BD (cases, n = 119) were recruited from health care settings located in southeast Victoria, Australia. Age-matched controls (n = 357, ratio 3:1) without BD were participants in the Geelong Osteoporosis Study drawn from the same geographical region. Lifetime history of BD was identified by semi-structured clinical interview (SCID-IV/NP). Previous 12-month falls data were obtained via questionnaire. Information on mobility, alcohol use, general health, medication use, blood pressure, body mass index, socioeconomic status and use of a walking aid was collected. Generalised Estimating Equations, binary and ordinal logistic regression were used to determine the odds ratio (OR) and 95% confidence interval (CI) for falls following adjustment for confounders. RESULTS: During the 12-month period, 34 (28.6%, median age 48.4 yr) cases and 70 (19.6%, median age 49.1 yr) controls reported one fall; 22 (18.5%) cases and 18 (5.0%) controls reported ≥ two falls (p < 0.001). Cases had 2.5-fold increased odds of at least one fall and 2.9-fold increased likelihood of increasing falls categories (0 vs. 1 vs. 2 +), compared to controls [adjOR 2.5, 95%CI (1.8, 3.4), adjOR OR 2.9, 95%CI (2.0, 4.1)]. CONCLUSION: Risk of falls was greater among women with BD. Balance training could be a research and clinical focus for falls prevention programs among women with bipolar disorder to prevent the detrimental outcomes associated with falling.

Anticonvulsant use and fracture: a case-control study.

OBJECTIVES: We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women. METHODS: Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders. RESULTS: In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women. CONCLUSIONS: Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.

Anticonvulsant use and bone health in a population-based study of men and women: cross-sectional data from the Geelong Osteoporosis Study.

BACKGROUND: Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based sample of men and women. METHODS: Data from 926 men (24-73 yr) and 1070 women (21-94 yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm2) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. RESULTS: Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI. CONCLUSION: Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.

Towards accurate exclusion of neonatal bacterial meningitis: a feasibility study of a novel 16S rDNA PCR assay.

BACKGROUND: PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay's potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the "field conditions" to attain a clinically useful level of specificity. METHODS: The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (Eppendorf™) replaced standard universal containers for collection of CSF to reduce environmental contamination. RESULTS: The assay's specificity was 90.5% in CSF collected into the snap-top tubes - up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study. CONCLUSIONS: A simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay's sensitivity and its negative predictive value.

Personality disorder increases risk of low quality of life among women with mental state disorders.

BACKGROUND: Limited data are available examining the relationship between mental state disorders (mood, anxiety, substance use, eating disorders), their co-occurrence with personality disorder (PD), and quality of life among women. We aimed to investigate these relationships in a sample of women from the community. METHOD: Women from the Geelong Osteoporosis Study (n = 717) were administered the Structured Clinical Interview for DSM-IV (SCID-I/NP and SCID-II) and the World Health Organisation Quality of Life scale (WHOQOL-BREF). Weight and height were measured and lifestyle and demographic factors were self-reported. Logistic regression models (odds ratios with 95% confidence intervals) were undertaken to investigate associations among groups (mental state disorders, co-occurring mental state disorders with PD, and controls) and the WHOQOL-BREF domains (physical, psychological, social, and environmental health) while testing for potential confounding. RESULTS: Results indicated that mental state disorders were associated with increased risk of low quality of life in physical, psychological, social, but not environmental domains, compared to controls. This risk was increased among women with co-occurring PD across all domains compared to both controls and those with mental state disorders. CONCLUSION: These findings add evidence suggesting poor quality of life is experienced by those with mental state disorders, and that this is worsened by the experience of co-occurring PD.

Lower-limb muscle strength: normative data from an observational population-based study.

BACKGROUND: The extent of muscle deterioration associated with ageing or disease can be quantified by comparison with appropriate reference data. The objective of this study is to present normative data for lower-limb muscle strength and quality for 573 males and 923 females aged 20-97 yr participating in the Geelong Osteoporosis Study in southeastern Australia. METHODS: In this cross-sectional study, measures of muscle strength for hip flexors and hip abductors were obtained using a Nicholas manual muscle tester, a hand-held dynamometer (HHD; kg). Leg lean mass was measured by dual energy x-ray absorptiometry (DXA; kg), and muscle quality calculated as strength/mass (N/kg). RESULTS: For both sexes, muscle strength and quality decreased with advancing age. Age explained 12.9-25.3% of the variance in muscle strength in males, and 20.8-24.6% in females; age explained less of the variance in muscle quality. Means and standard deviations for muscle strength and quality for each muscle group are reported by age-decade for each sex, and cutpoints equivalent to T-scores of - 2.0 and - 1.0 were derived using data from young males (n = 89) and females (n = 148) aged 20-39 years. CONCLUSIONS: These data will be useful for quantifying the extent of dynapenia and poor muscle quality among adults in the general population in the face of frailty, sarcopenia and other age-related muscle dysfunction.

Diet quality, dietary patterns and short sleep duration: a cross-sectional population-based study.

OBJECTIVE: To examine the cross-sectional association between habitual diet quality, dietary patterns and sleep duration. METHODS: A cross-sectional study of 838 men and 1065 women participating in a large, population-based cohort study, the Geelong Osteoporosis Study. A diet quality score (DQS) was derived from answers to a food-frequency questionnaire, and a factor analysis identified habitual dietary patterns. Self-reported sleep duration was dichotomized into 'short sleep duration' (< 7 h/night) and 'adequate sleep duration' (≥ 7 h/night). Sleep duration was also grouped into predetermined cut-off ranges (< 5, 5.01-6, 6.01-7, 7.01-8, 8.01-9, 9.01-10 and ≥ 10.01 h /night) to explore the relationship between sleep duration, DQS and dietary patterns. RESULTS: 363 (34.0%) women and 339 (36.1%) men were identified with short sleep duration. After adjustments for age, socioeconomic status, education, physical activity and body mass index, each standard deviation increase in the factor score for traditional dietary pattern was associated with a 13% reduced odds for short sleep duration in men. In women, each standard deviation increase in DQS score was associated with a 21% reduced odds for short sleep duration. In women, adequate sleep was related to higher modern dietary pattern scores when compared both with excessive sleep duration (> 9 h) and shorter sleep duration (< 7 h). CONCLUSION: Diet quality score was associated with adequate sleep duration (≥ 7 h) and reduced odds for short sleep duration (< 7 h) in Australian women.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men.

Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20-96 year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94 year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.

Pattern of psychotropic medication use over two decades in Australian women.

OBJECTIVE: Few population-based studies have been used to investigate secular trends in psychotropic medication use. Therefore, the aim of this study was to examine psychotropic medication use over time using data from the Geelong Osteoporosis Study, an on-going, population-based, cohort study of Australian women. METHODS: Of the 1494 women recruited at Time 1 (1993-1997), self-reported medication use from Time 2 (2004-2008) and/or Time 3 (2011-2014) was available for 889 women. Prevalence of antidepressant/antipsychotic/anxiolytic/sedative/anticonvulsant use by age and cohort strata was calculated using bootstrapping methods. Simultaneous age-cohort patterns were evaluated using logistic regression techniques. RESULTS: The prevalence of any psychotropic medication use increased from 8.0% (95% confidence interval = [6.3, 9.8]) at Time 1 to 26.0% (95% confidence interval = [22.4, 29.4]) at Time 3, translating to a 4.3-fold increase in the likelihood of psychotropic medication use over the study period (odds ratio = 4.3, 95% confidence interval = [3.2, 5.8], p < 0.001). This increase was driven by the use of antidepressants (odds ratio = 6.4, 95% confidence interval = [4.2, 9.5], p < 0.001) and anticonvulsants (odds ratio = 4.4, 95% confidence interval = [1.8, 11.1]) and modest increases in the use of anxiolytic agents (odds ratio = 1.9, 95% confidence interval = [1.1, 3.1]) and sedatives (odds ratio = 1.7, 95% confidence interval = [1.6, 1.9]). The prevalence of any psychotropic medication use increased with increasing age (40-59.9 years: odds ratio = 1.9, 95% confidence interval = [1.5, 2.6]; 60-79.9 years: odds ratio = 2.6, 95% confidence interval = [1.9, 3.5], compared to the 20- to 39.9-year group). Use of selective serotonin reuptake inhibitors increased dramatically over the study period (odds ratio = 15.3, 95% confidence interval = [7.0, 33.4]). CONCLUSION: Use of psychotropic medication has increased substantially over the past two decades, especially among older women. Further investigations into the correlates and outcomes of the increased use of psychotropic medications are warranted.

The prevalence, age distribution and comorbidity of personality disorders in Australian women.

OBJECTIVE: We aimed to describe the prevalence and age distribution of personality disorders and their comorbidity with other psychiatric disorders in an age-stratified sample of Australian women aged ⩾25 years. METHODS: Individual personality disorders (paranoid, schizoid, schizotypal, histrionic, narcissistic, borderline, antisocial, avoidant, dependent, obsessive-compulsive), lifetime mood, anxiety, eating and substance misuse disorders were diagnosed utilising validated semi-structured clinical interviews (Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition and Structured Clinical Interview for DSM-IV Axis II Personality Disorders). The prevalence of personality disorders and Clusters were determined from the study population ( n = 768), and standardised to the Australian population using the 2011 Australian Bureau of Statistics census data. Prevalence by age and the association with mood, anxiety, eating and substance misuse disorders was also examined. RESULTS: The overall prevalence of personality disorders in women was 21.8% (95% confidence interval [CI]: 18.7, 24.9). Cluster C personality disorders (17.5%, 95% CI: 16.0, 18.9) were more common than Cluster A (5.3%, 95% CI: 3.5, 7.0) and Cluster B personality disorders (3.2%, 95% CI: 1.8, 4.6). Of the individual personality disorders, obsessive-compulsive (10.3%, 95% CI: 8.0, 12.6), avoidant (9.3%, 95% CI: 7.1, 11.5), paranoid (3.9%, 95% CI: 3.1, 4.7) and borderline (2.7%, 95% CI: 1.4, 4.0) were among the most prevalent. The prevalence of other personality disorders was low (⩽1.7%). Being younger (25-34 years) was predictive of having any personality disorder (odds ratio: 2.36, 95% CI: 1.18, 4.74), as was being middle-aged (odds ratio: 2.41, 95% CI: 1.23, 4.72). Among the strongest predictors of having any personality disorder was having a lifetime history of psychiatric disorders (odds ratio: 4.29, 95% CI: 2.90, 6.33). Mood and anxiety disorders were the most common comorbid lifetime psychiatric disorders. CONCLUSIONS: Approximately one in five women was identified with a personality disorder, emphasising that personality disorders are relatively common in the population. A more thorough understanding of the distribution of personality disorders and psychiatric comorbidity in the general population is crucial to assist allocation of health care resources to individuals living with these disorders.

Statin and Aspirin Use and the Risk of Mood Disorders among Men.

BACKGROUND: There is a growing understanding that depression is associated with systemic inflammation. Statins and aspirin have anti-inflammatory properties. Given these agents have been shown to reduce the risk of a number of diseases characterized by inflammation, we aimed to determine whether a similar relationship exists for mood disorders (MD). METHODS: This study examined data collected from 961 men (24-98 years) participating in the Geelong Osteoporosis Study. MD were identified using a semistructured clinical interview (SCID-I/NP). Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. Two study designs were utilized: a nested case-control and a retrospective cohort study. RESULTS: In the nested case-control study, exposure to statin and aspirin was documented for 9 of 142 (6.3%) cases and 234 of 795 (29.4%) controls (P < .001); after adjustment for age, exposure to these anti-inflammatory agents was associated with reduced likelihood of MD (OR 0.2, 95%CI 0.1-0.5). No effect modifiers or other confounders were identified. In the retrospective cohort study of 836 men, among the 210 exposed to statins or aspirin, 6 (2.9%) developed de novo MD during 1000 person-years of observation, whereas among 626 nonexposed, 34 (5.4%) developed de novo MD during 3071 person-years of observation. The hazard ratio for de novo MD associated with exposure to anti-inflammatory agents was 0.55 (95%CI 0.23-1.32). CONCLUSIONS: This study provides both cross-sectional and longitudinal evidence consistent with the hypothesis that statin and aspirin use is associated with a reduced risk of MD.

The addition of depression to the Framingham Risk Equation model for predicting coronary heart disease risk in women.

BACKGROUND: Depression is widely considered to be an independent and robust predictor of Coronary Heart Disease (CHD), however is seldom considered in the context of formal risk assessment. We assessed whether the addition of depression to the Framingham Risk Equation (FRE) improved accuracy for predicting 10-year CHD in a sample of women. DESIGN: A prospective, longitudinal design comprising an age-stratified, population-based sample of Australian women collected between 1993 and 2011 (n=862). METHODS: Clinical depressive disorder was assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-I/NP), using retrospective age-of-onset data. A composite measure of CHD included non-fatal myocardial infarction, unstable angina coronary intervention or cardiac death. Cox proportional-hazards regression models were conducted and overall accuracy assessed using area under receiver operating characteristic (ROC) curve analysis. RESULTS: ROC curve analyses revealed that the addition of baseline depression status to the FRE model improved its overall accuracy (AUC:0.77, Specificity:0.70, Sensitivity:0.75) when compared to the original FRE model (AUC:0.75, Specificity:0.73, Sensitivity:0.67). However, when calibrated against the original model, the predicted number of events generated by the augmented version marginally over-estimated the true number observed. CONCLUSIONS: The addition of a depression variable to the FRE equation improves the overall accuracy of the model for predicting 10-year CHD events in women, however may over-estimate the number of events that actually occur. This model now requires validation in larger samples as it could form a new CHD risk equation for women.

The prevalence and age of onset of psychiatric disorders in Australian men.

OBJECTIVE: Given the burden of common psychiatric disorders and their consequent service and planning requirements, it is important to have a thorough knowledge of their distribution and characteristics in the population. Thus, we aimed to report the prevalence and age of onset of mood, anxiety and substance-use disorders in an age-stratified representative sample of Australian men. METHOD: Psychiatric disorders (mood, anxiety and substance-use disorders) were diagnosed utilising a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Non-Patient Edition) for 961 men aged 24-98 years enrolled in the Geelong Osteoporosis Study. The lifetime and current prevalence of these disorders was determined from the study population and standardised to 2006 census data for Australia. RESULTS: Approximately one in three men (28.8%, 95% confidence interval [CI] = [26.8%, 30.8%]) reported a lifetime history of any psychiatric disorder, with mood disorders (18.2%, 95% CI = [15.2%, 21.2%]) being more prevalent than anxiety (7.2%, 95% CI = [5.0%, 9.4%]) and substance-use disorders (12.9%, 95% CI = [9.7%, 16.0%]). Approximately 8.7% (95% CI = [7.5%, 10.0%]) were identified as having a current disorder, with 3.8% (95% interquartile range [IQR] = [2.2%, 5.4%]), 2.4% (95% CI = [1.1%, 3.8%]) and 3.4% (95% CI = [1.8%, 4.9%]) meeting criteria for current mood, anxiety and substance-use disorders, respectively. The median age of onset for mood disorders was 37.5 years (IQR = 27.0-48.0 years), 25.0 years (IQR = 20.0-40.3 years) for anxiety and 22.0 years (IQR = 18.0-34.3 years) for substance-use disorders. CONCLUSION: This study reports the lifetime and current prevalence of psychiatric disorders in the Australian male population. These findings emphasise the extent of the burden of these disorders in the community.

Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak.

BACKGROUND: Isolates of methicillin-resistant Staphylococcus aureus (MRSA) belonging to a single lineage are often indistinguishable by means of current typing techniques. Whole-genome sequencing may provide improved resolution to define transmission pathways and characterize outbreaks. METHODS: We investigated a putative MRSA outbreak in a neonatal intensive care unit. By using rapid high-throughput sequencing technology with a clinically relevant turnaround time, we retrospectively sequenced the DNA from seven isolates associated with the outbreak and another seven MRSA isolates associated with carriage of MRSA or bacteremia in the same hospital. RESULTS: We constructed a phylogenetic tree by comparing single-nucleotide polymorphisms (SNPs) in the core genome to a reference genome (an epidemic MRSA clone, EMRSA-15 [sequence type 22]). This revealed a distinct cluster of outbreak isolates and clear separation between these and the nonoutbreak isolates. A previously missed transmission event was detected between two patients with bacteremia who were not part of the outbreak. We created an artificial "resistome" of antibiotic-resistance genes and demonstrated concordance between it and the results of phenotypic susceptibility testing; we also created a "toxome" consisting of toxin genes. One outbreak isolate had a hypermutator phenotype with a higher number of SNPs than the other outbreak isolates, highlighting the difficulty of imposing a simple threshold for the number of SNPs between isolates to decide whether they are part of a recent transmission chain. CONCLUSIONS: Whole-genome sequencing can provide clinically relevant data within a time frame that can influence patient care. The need for automated data interpretation and the provision of clinically meaningful reports represent hurdles to clinical implementation. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.).

Changes in gait performance over several years are associated with recurrent falls status in community-dwelling older women at high risk of fracture.

BACKGROUND: Gait analysis is a recommended geriatric assessment for falls risk and sarcopenia; however, previous research utilises measurements at a single time point only. It is presently unclear how changes in gait over several years influence risk of recurrent falls in older adults. METHODS: We investigated 135 female volunteers (mean age±SD: 76.7±5.0 years; range: 70-92 years) at high risk of fracture. Gait parameters (speed, cadence, step length, step width, swing time and double support phase) were assessed using the GAITRite Electronic Walkway System at four annual clinics over ∼3.7±0.5 years. Participants reported incident falls monthly for 3.7±1.2 years. RESULTS: Increasing gait speed (odds ratio: 0.96; 95% confidence interval 0.93, 0.99) and step length (0.87; 0.77, 0.98) from baseline to final follow-up was associated with reduced likelihood of being a recurrent faller over the study period. No significant associations were observed for baseline gait parameters (all P≥0.05). At the second follow-up (2.8±0.6 years), an increase in swing time (0.65; 0.43, 0.98) was associated with reduced likelihood, while an increase in double support phase (1.31; 1.04, 1.66) was associated with increased likelihood, for being a recurrent faller in the subsequent 1.3 years following this time point. CONCLUSION: Changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older women at high risk of fracture. Further research is required to develop gait monitoring guidelines and gait parameter decline cut points that may be utilised by clinicians to identify older adults at risk of incident falls and sarcopenia.