Lifestyle factors associated concurrently and prospectively with co-morbid cardiovascular disease in a population-based cohort of colorectal cancer survivors

Aims To assess self-reported lifetime prevalence of cardiovascular disease (CVD) among colorectal cancer survivors, and examine the cross-sectional and prospective associations of lifestyle factors with co-morbid CVD. Methods Colorectal cancer survivors were recruited (n = 1966). Data were collected at approximately 5, 12, 24 and 36 months post-diagnosis. Cross-sectional findings included six CVD categories (hypercholesterolaemia, hypertension, diabetes, heart failure, kidney disease and ischaemic heart disease (IHD)) at 5 months post-diagnosis. Longitudinal outcomes included the probability of developing (de novo) co-morbid CVD by 36 months post-diagnosis. Lifestyle factors included body mass index, physical activity, television (TV) viewing, alcohol consumption and smoking. Results Co-morbid CVD prevalence at 5 months post-diagnosis was 59%, and 16% of participants with no known CVD at the baseline reported de novo CVD by 36 months. Obesity at the baseline predicted de novo hypertension (odds ratio [OR] = 2.20, 95% confidence intervals [CI] = 1.09, 4.45) and de novo diabetes (OR = 6.55, 95% CI = 2.19, 19.53). Participants watching >4 h of TV/d at the baseline (compared with <2 h/d) were more likely to develop ischaemic heart disease by 36 months (OR = 5.51, 95% CI = 1.86, 16.34). Conclusion Overweight colorectal cancer survivors were more likely to suffer from co-morbid CVD. Interventions focusing on weight management and other modifiable lifestyle factors may reduce functional decline and improve survival.

Back to basics: Informing the public of co-morbid physical health problems in those with mental illness

Abstract OBJECTIVE: Those with mental illness are at increased risk of physical health problems. The current study aimed to examine the information available online to the Australian public about the increased risk and consequences of physical illness in those with mental health problems and the services available to address these co-morbidities. METHODS: A structured online search was conducted with the search engine Google Australia (www.google.com.au) using generic search terms 'mental health information Australia', 'mental illness information Australia', 'depression', 'anxiety', and 'psychosis'. The direct content of websites was examined for information on the physical co-morbidities of mental illness. All external links on high-profile websites [the first five websites retrieved under each search term (n = 25)] were examined for information pertaining to physical health. RESULTS: Only 4.2% of websites informing the public about mental health contained direct content information about the increased risk of physical co-morbidities. The Australian Government's Department of Health and Ageing site did not contain any information. Of the high-profile websites, 62% had external links to resources about physical health and 55% had recommendations or resources for physical health. Most recommendations were generic. CONCLUSIONS: Relative to the seriousness of this problem, there is a paucity of information available to the public about the increased physical health risks associated with mental illness. Improved public awareness is the starting point of addressing this health inequity.

Molecular Genetic Studies of Melanocortin Receptors in Morbid Obesity

The prevalence of obesity is increasing at an alarming rate in all age groups worldwide. Obesity is a serious health problem due to increased risk of morbidity and mortality. Although environmental factors play a major role in the development of obesity, the identification of rare monogenic defects in human genes have confirmed that obesity has a strong genetic component. Mutations have been identified in genes encoding proteins of the leptin-melanocortin signaling system, which has an important role in the regulation of appetite and energy balance. The present study aimed at identifying mutations and genetic variations in the melanocortin receptors 2-5 and other genes active on the same signaling pathway accounting for severe early-onset obesity in children and morbid obesity in adults. The main achievement of this thesis was the identification of melanocortin-4 receptor (MC4R) mutations in Finnish patients. Six pathogenic MC4R mutations (308delT, P299H, two S127L and two -439delGC mutations) were identified, corresponding to a prevalence of 3% in severe early-onset obesity. No obesity causing MC4R mutations were found among patients with adult-onset morbid obesity. The MC4R 308delT deletion is predicted to result in a grossly truncated nonfunctional receptor of only 107 amino acids. The C-terminal residues, which are important in MC4R cell surface targeting, are totally absent from the mutant 308delT receptor. In vitro functional studies supported a pathogenic role for the S127L mutation since agonist induced signaling of the receptor was impaired. Cell membrane localization of the S127L receptor did not differ from that of the wild-type receptor, confirming that impaired function of the S127L receptor was due to reduced signaling properties. The P299H mutation leads to intracellular retention of the receptor. The -439delGC deletion is situated at a potential nescient helix-loop-helix 2 (NHLH2) -binding site in the MC4R promoter. It was demonstrated that the transcription factor NHLH2 binds to the consensus sequence at the -439delGC site in vitro, possibly resulting in altered promoter activity. Several genetic variants were identified in the melanocortin-3 receptor (MC3R) and pro-opiomelanocortin (POMC) genes. These polymorphisms do not explain morbid obesity, but the results indicate that some of these genetic variations may be modifying factors in obesity, resulting in subtle changes in obesity-related traits. A risk haplotype for obesity was identified in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene through a candidate gene single nucleotide polymorphism (SNP) genotyping approach. An ENPP1 haplotype, composed of SNPs rs1800949 and rs943003, was shown to be significantly associated with morbid obesity in adults. Accordingly, the MC3R, POMC and ENPP1 genes represent examples of susceptibility genes in which genetic variants predispose to obesity. In conclusion, pathogenic mutations in the MC4R gene were shown to account for 3% of cases with severe early-onset obesity in Finland. This is in line with results from other populations demonstrating that mutations in the MC4R gene underlie 1-6% of morbid obesity worldwide. MC4R deficiency thus represents the most common monogenic defect causing human obesity reported so far. The severity of the MC4-receptor defect appears to be associated with time of onset and the degree of obesity. Classification of MC4R mutations may provide a useful tool when predicting the outcome of the disease. In addition, several other genetic variants conferring susceptibility to obesity were detected in the MC3R, MC4R, POMC and ENPP1 genes.

Morbid obesity in total hip arthroplasty: Redefining outcomes for operative time, length of stay, and readmission

Background The incidence of obesity amongst patients presenting for elective Total Hip Arthroplasty (THA) has increased in the last decade and the relationship between obesity and the need for joint replacement has been demonstrated. This study evaluates the effects of morbid obesity on outcomes following primary THA by comparing short-term outcomes in THA between a morbidly obese (BMI ≥40) and a normal weight (BMI 18.5 - <25) cohort at our institution between January 2003 and December 2010. Methods Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission and length of readmission were compared. Results Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (p=0.002). Post-operatively there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI ≥40 compared with 2.7% (p= 0.005) as well as a 5.1 fold increase in surgery related readmitted bed days - 0.32 bed days per patient for normal weight compared with 1.64 per patient for the morbidly obese (p=0.026). Conclusion Morbidly obese patients present a technical challenge and likely this and the resultant complications are underestimated. More work needs to be performed in order to enable suitable allocation of resources.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS:

A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients.

METHODS:

For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n?=?15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients.

RESULTS:

Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n?=?10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results.

CONCLUSIONS/INTERPRETATION:

Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Trends in Morbid Obesity and in Bariatric Surgeries Covered by the Brazilian Public Health System

Obesity is an increasingly serious public health problem on a global level. Morbid obesity, defined as a body mass index greater than 40 kg/m(2), is associated with increased mortality and a high burden of obesity-related morbidities. To study the prevalence of morbid obesity in Brazil, three national anthropometric surveys were reanalyzed. Data about bariatric surgeries were obtained from the Ministry of Health Hospital Information System, which is available online. A 255% rise in the prevalence of morbid obesity was observed, starting at 0.18% in 1975-1976 and growing to 0.33% in 1989 and 0.64% in 2002-2003. There was a higher rate in the South in the first two surveys, but the prevalence in the Southeast rose steadily, reaching 0.77% in 2002-2003 and overtaking the South. Since 1999, the Brazilian Unified Health System has covered surgical treatment for morbid obesity. From 2000 to 2006, there was a sixfold increase in the number of surgeries, which topped the 2,500 mark in 2006. The geographic distribution of these surgeries is heavily concentrated in the Southeast, the most developed region of Brazil, where there is also the highest prevalence of morbid obesity. This was followed by the Southern region. The figures for the rise in morbid obesity in Brazil are startling, especially the increase among men. This is a situation that calls for further study, alongside measures to encourage the adoption of healthy lifestyles. Preventive measures aimed at slowing down or reversing the obesity epidemic are urgently required.

Co-morbid cardiovascular disease and depression : sequence of disease onset is linked to mental but not physical self-rated health. Results from a cross-sectional, population-based study

Purpose: Self-rated health has been linked to important health and survival outcomes in individuals with co-morbid depression and cardiovascular disease (CVD). It is not clear how the timing of depression onset relative to CVD onset affects this relationship. We aimed to first identify the prevalence of major depressive disorder (MDD) preceding CVD and secondly determine whether sequence of disease onset is associated with mental and physical self-rated health. Methods: This study utilised cross-sectional, populationbased data from 224 respondents of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). Participants were those diagnosed with MDD and reported ever having a heart/circulatory condition over their lifetime. Age of onset was reported for each condition. Logistic regression was used to explore differences in self-rated mental and physical health for those reporting pre-cardiac and post-cardiac depression. Results: The proportion of individuals in whom MDD preceded CVD was 80.36% (CI: 72.57-88.15). One-fifth (19.64%, CI: 11.85-27.42) reported MDD onset at the time of, or following, CVD. After controlling for covariates, the final model demonstrated that those reporting post-cardiac depression were significantly less likely to report poor selfrated mental health (OR:0.36, CI: 0.14-0.93) than those with pre-existing depression. No significant differences were found in self-rated physical health between groups (OR:0.90 CI: 0.38-2.14). Conclusions: MDD is most common prior to the onset of CVD. Further, there is an association between pre-morbid MDD and poorer self-rated mental health. To our knowledge, this is the first time this has been demonstrated in a national, population-based survey. As self-rated health has been shown to predict important outcomes such as survival, we recommend that those with MDD be identified as vulnerable to CVD onset and poorer health outcomes

Co-morbid depression is associated with poor work outcomes in persons with cardiovascular disease (CVD) : a large, nationally representative survey in the Australian population

Background: Co-morbid major depressive disorder (MDD) and cardiovascular disease (CVD) is associated with poor clinical and psychological outcomes. However, the full extent of the burden of, and interaction between, this co-morbidity on important vocational outcomes remains less clear, particularly at the population level. We examine the association of co-morbid MDD with work outcomes in persons with and without CVD.

Methods. This study utilised cross-sectional, population-based data from the 2007 Australian National Survey of Mental Health and Wellbeing (n = 8841) to compare work outcomes of individuals with diagnostically-defined MDD and CVD, MDD but not CVD, CVD but not MDD, with a reference group of "healthy" Australians. Workforce participation was defined as being in full- or part-time employment. Work functioning was measured using a WHO Disability Assessment Schedule item. Absenteeism was assessed using the 'days out of role' item.

Results: Of the four groups, those with co-morbid MDD and CVD were least likely to report workforce participation (adj OR:0.4, 95% CI: 0.3-0.6). Those with MDD only (adj OR:0.8, 95% CI:0.7-0.9) and CVD only (adj OR:0.8, 95% CI: 0.6-0.9) also reported significantly reduced odds of participation. Employed individuals with co-morbid MDD and CVD were 8 times as likely to experience impairments in work functioning (adj OR:8.1, 95% CI: 3.8- 17.3) compared with the reference group. MDD was associated with a four-fold increase in impaired functioning. Further, individuals with co-morbid MDD and CVD reported greatest likelihood of workplace absenteeism (adj. OR:3.0, 95% CI: 1.4-6.6). Simultaneous exposure to MDD and CVD conferred an even greater likelihood of poorer work functioning.

Conclusions: Co-morbid MDD and CVD is associated with significantly poorer work outcomes. Specifically, the effects of these conditions on work functioning are synergistic. The development of specialised treatment programs for those with co-morbid MDD and CVD is required.

The health-related quality of life burden of co-morbid cardiovascular disease and major depressive disorder in Australia : findings from a population-based, cross-sectional study

Purpose Health-related quality of life (HRQOL) can be significantly impaired by the presence of chronic conditions such as cardiovascular disease (CVD) and major depressive disorder (MDD). The aim of this paper was to (1) identify differences in HRQOL between individuals with CVD, MDD, or both, compared to a healthy reference group, (2) establish whether the influence of co-morbid MDD and CVD on HRQOL is additive or synergistic and (3) determine the way in which depression severity interacts with CVD to influence overall HRQOL.

Methods Population-based data from the 2007 Australian National Survey of Mental Health and Well-being (NSMHWB) (n = 8841) were used to compare HRQOL of individuals with MDD and CVD, MDD but not CVD, CVD but not MDD, with a healthy reference group. HRQOL was measured using the Assessment of Quality of Life (AQOL). MDD was identified using the Composite International Diagnostic Interview (CIDI 3.0).

Results Of all four groups, individuals with co-morbid CVD and depression reported the greatest deficits in AQOL utility scores (Coef: −0.32, 95% CI: −0.40, −0.23), after adjusting for covariates. Those with MDD only (Coef: −0.27, 95% CI: −0.30, −0.24) and CVD only (Coef: −0.08, 95% CI: −0.11, −0.05) also reported reduced AQOL utility scores. Second, the influence of MDD and CVD on HRQOL was shown to be additive, rather than synergistic. Third, a significant dose–response relationship was observed between depression severity and HRQOL. However, CVD and depression severity appeared to act independently of each other in impacting HRQOL.

Conclusions HRQOL is greatly impaired in individuals with co-morbid MDD and CVD; these conditions appear to influence HRQOL in an additive fashion. HRQOL alters with depression severity, therefore treating depression and improving HRQOL is of clinical importance.

Morbid obesity in women on the rise : an observational, population-based study

Background The obesity epidemic is generally monitored by the proportion of the population whose body mass index (BMI) exceeds 30 kg/m2 but this masks the growing proportion of those who are morbidly obese. This issue is important as the adverse health risks amplify as the level of obesity increases. The aim of this study was to determine how the prevalence of morbid obesity (BMI >= 40.0 kg/m2) has changed over a decade among women living in south-eastern Australia.

Methods BMI was determined for women in the Geelong Osteoporosis study (GOS) during two time periods, a decade apart. Height and weight were measured for 1,494 women (aged 20--94 years) during 1993--7 and for 1,076 women (aged 20--93 years), 2004--8, and the BMI calculated as weight in kilograms divided by the square of the height in metres (kg/m2). Prevalence estimates were age-standardised to enable direct comparisons.

Results Mean BMI increased from 26.0 kg/m2 (95%CI 25.7-26.3) in 1993--7, to 27.1 kg/m2 (95%CI 26.8-27.4) in 2004--8. During this period, the prevalence of morbid obesity increased from 2.5% to 4.2% and the standardised morbidity ratio for morbid obesity was 1.69 (95%CI 1.26-2.27). Increases in mean BMI and prevalence of morbid obesity were observed for all ages and across the socioeconomic spectrum.

Conclusions These findings reveal that over a decade, there has been an increase in mean BMI among women residing in south-eastern Australia, resulting in a measurable increase in the prevalence of morbid obesity.

Brief report: children with ADHA without co-morbid autism do not have impaired motor proficiency on the Movement Assessment Battery for Children

Motor proficiency was investigated in a sample of children with Attention Deficit Hyperactivity Disorder-Combined type (ADHD-CT) without autism. Accounting for the influence of co-morbid autistic symptoms in ADHD motor studies is vital given that motor impairment has been linked to social–communication symptoms in children who have co-morbid ADHD and autistic-like symptoms. Two groups of children aged between 7–14 years were recruited; children with ADHD-CT (n = 16; mean age 10 years, 7 months [SD = 1 year, 10 months]) and a typically developing (n = 16; mean age 10 years, 6 months [SD = 2 years, 6 months]) group. Motor proficiency was measured using the Movement Assessment Battery for Children-2nd Edition, ADHD symptoms were measured using the Conner’s Parent Rating Scale. Children with ADHD-CT who had been screened for co-morbid autism did not display motor difficulties on the MABC-2. Higher levels of inattention, but not hyperactivity or impulsivity were associated with poorer motor performance. These findings provide indirect evidence that the motor problems that children with ADHD experience may be related to co-occurring social responsiveness impairments.

Co-morbid depression and chronic illness related to coping and physical and mental health status

A partial latent structural regression analysis was used to evaluate the role of coping resources, depression, diet and exercise on mental and physical health status. The sample consisted of 113 participants (59 females and 54 males) with a mean age of 59.38 years (SD = 10.52). Coping resources, depression and exercise explained 52 and 26% of the variance in mental and physical health status, respectively. Fewer coping resources predicted higher levels of depression and both predicted worse mental health. Only higher levels of depression predicted worse physical health status. There were also significant indirect effects of coping on mental and physical health status through depression. The development of cognitive, social and emotional coping strategies is important for managing depression and supporting positive mental health. These results highlight the important role of health psychologists in the care of individuals with chronic illness. Additionally, the management of depression is important in maintaining positive physical health.