Common mental disorder and suicidality among doctors: differences by specialty.

BACKGROUND: Common mental disorders (CMDs) and suicidal ideation (SI) are prevalent among doctors, yet limited evidence exists investigating the relationship of specialty area to these outcomes. AIMS: This study aimed to determine the prevalence of likely CMD and SI among doctors and to investigate whether likelihood of these outcomes varied by area of medical specialty. METHODS: A secondary analysis of a representative national survey of 12,252 Australian doctors was conducted. Demographic and work-related variables, SI and CMD (GHQ-28), were assessed among doctors (n = 7037; 57%) working in a range of specialty areas. Logistic regression was used to examine the association between specialty and mental health outcomes in unadjusted and adjusted models. RESULTS: Almost one-quarter of doctors (n = 1560; 23%) reported symptom levels indicating likely CMD whilst 9% (n = 667) reported SI in the last year. Doctors in surgery (adjusted odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.54-0.97, P = 0.03) were at significantly lower risk of CMD than General Practitioners (GPs), whilst doctors in anaesthetics (adjusted OR = 1.45; 95% CI 1.09-1.93, P = 0.01) and paediatrics (adjusted OR = 1.88; 95% CI 1.02-3.47, P = 0.04) were at significantly higher risk of experiencing SI compared to GPs after accounting for confounders. CONCLUSIONS: Results demonstrated that doctors in Australia working in certain specialties, specifically anaesthetics and paediatrics, were at significantly greater risk of suicidal ideation compared to GPs after accounting for confounders. Interventions to address CMD and SI among doctors in all specialties remain urgently needed.

Economic evaluations of Internet interventions for mental health: a systematic review.

BACKGROUND: Internet interventions are assumed to be cost-effective. However, it is unclear how strong this evidence is, and what the quality of this evidence is. METHOD: A comprehensive literature search (1990-2014) in Medline, EMBASE, the Cochrane Central Register of Controlled Trials, NHS Economic Evaluations Database, NHS Health Technology Assessment Database, Office of Health Economics Evaluations Database, Compendex and Inspec was conducted. We included economic evaluations alongside randomized controlled trials of Internet interventions for a range of mental health symptoms compared to a control group, consisting of a psychological or pharmaceutical intervention, treatment-as-usual (TAU), wait-list or an attention control group. RESULTS: Of the 6587 abstracts identified, 16 papers met the inclusion criteria. Nine studies featured a societal perspective. Results demonstrated that guided Internet interventions for depression, anxiety, smoking cessation and alcohol consumption had favourable probabilities of being more cost-effective when compared to wait-list, TAU, group cognitive behaviour therapy (CBGT), attention control, telephone counselling or unguided Internet CBT. Unguided Internet interventions for suicide prevention, depression and smoking cessation demonstrated cost-effectiveness compared to TAU or attention control. In general, results from cost-utility analyses using more generic health outcomes (quality of life) were less favourable for unguided Internet interventions. Most studies adhered reasonably to economic guidelines. CONCLUSIONS: Results of guided Internet interventions being cost-effective are promising with most studies adhering to publication standards, but more economic evaluations are needed in order to determine cost-effectiveness of Internet interventions compared to the most cost-effective treatment currently available.

Ovarian hyperstimulation syndrome on the acute medical unit: a problem-based review.

Ovarian Hyperstimulation Syndrome (OHSS) is a spectrum of clinical features typically resulting from assisted conception techniques. With 2.35% of all live births in the UK resulting from in-vitro fertilisation (IVF), OHSS is on the rise. Moreover, there has been an increase in the presentation of its complications to GP surgeries and unscheduled acute care services nationwide. This review will discuss signs and symptoms of the increasingly common and potentially fatal complications of OHSS, namely pleural effusion, ascites and thromboembolic events. With such propensity toward critical, life-threatening events it is not only prudent to recognise the population at risk, but also to be aware of the signs, symptoms and complications to expedite treatment and ensure optimum outcome.

Are illness perceptions related to future healthcare expenditure in patients with somatoform disorders?

BACKGROUND: Somatoform disorders are costly for society in terms of increased healthcare expenditure. Patients' illness perceptions have been found to play a role in somatoform disorders. However, it is unclear whether illness perceptions predict higher health costs in these patients. METHOD: A total of 1785 primary care patients presenting a new health complaint completed a questionnaire on their illness perceptions and emotional distress before the consultation. The physicians completed a questionnaire for each patient on diagnostics after the consultation. In a stratified subsample, physician interviewers established diagnoses of DSM-IV somatization and undifferentiated somatoform disorders (n = 144) using the Schedules for Clinical Assessment in Neuropsychiatry. Healthcare expenditure was obtained from Danish health registers for a 2-year follow-up period. RESULTS: Patients had more negative perceptions of their well-defined physical health problems when they had a co-morbid somatoform disorder. A strong illness identity [ß = 0.120, 95% confidence interval (CI) 0.029-0.212, p = 0.012], perceived negative consequences (ß = 0.010, 95% CI 0.001-0.019, p = 0.024), a long timeline perspective (ß = 0.013, 95% CI 0.005-0.021, p = 0.001), low personal control (ß = - 0.009, 95% CI -0.015 to -0.002, p = 0.011) and negative emotional representations (ß = 0.009, 95% CI 0.002-0.017, p = 0.020) predicted healthcare expenditure in somatoform disorders. CONCLUSIONS: The results suggest that illness perceptions play a role in the perpetuation of symptoms in somatoform disorders and predict higher future healthcare expenditure among a subgroup of these patients.

Responses of anaerobic rumen fungal diversity (phylum Neocallimastigomycota) to changes in bovine diet.

AIMS: Anaerobic rumen fungi (Neocallimastigales) play important roles in the breakdown of complex, cellulose-rich material. Subsequent decomposition products are utilized by other microbes, including methanogens. The aim of this study was to determine the effects of dietary changes on anaerobic rumen fungi diversity. METHODS AND RESULTS: Altered diets through increasing concentrate/forage (50 : 50 vs 90 : 10) ratios and/or the addition of 6% soya oil were offered to steers and the Neocallimastigales community was assessed by PCR-based fingerprinting with specific primers within the barcode region. Both a decrease in fibre content and the addition of 6% soya oil affected Neocallimastigales diversity within solid and liquid rumen phases. The addition of 6% soya oil decreased species richness. Assemblages were strongly affected by the addition of 6% soya oil, whereas unexpectedly, the fibre decrease had less effect. Differences in volatile fatty acid contents (acetate, propionate and butyrate) were significantly associated with changes in Neocallimastigales assemblages between the treatments. CONCLUSIONS: Diet clearly influences Neocallimastigales assemblages. The data are interpreted in terms of interactions with other microbial groups involved in fermentation processes within the rumen. SIGNIFICANCE AND IMPACT OF THE STUDY: Knowledge on the influence of diet on anaerobic fungi is necessary to understand changes in microbial processes occurring within the rumen as this may impact on other rumen processes such as methane production.

Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.

All-trans-retinoic acid (ATRA)-based differentiation therapy of acute promyelocytic leukemia (APL) represents one of the most clinically effective examples of precision medicine and the first example of targeted oncoprotein degradation. The success of ATRA in APL, however, remains to be translated to non-APL acute myeloid leukemia (AML). We previously showed that aberrant histone modifications, including histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) methylation, were associated with this lack of response and that epigenetic therapy with small molecule inhibitors of the H3K4 demethylase LSD1/KDM1A could reprogram AML cells to respond to ATRA. Serving as the enzymatic component of Polycomb Repressive Complex 2, EZH2/KMT6A methyltransferase plays a critical role in normal hematopoiesis by affecting the balance between self-renewal and differentiation. The canonical function of EZH2 is methylation of H3K27, although important non-canonical roles have recently been described. EZH2 mutation or deregulated expression has been conclusively demonstrated in the pathogenesis of AML and response to treatment, thus making it an attractive therapeutic target. In this study, we therefore investigated whether inhibition of EZH2 might also improve the response of non-APL AML cells to ATRA-based therapy. We focused on GSK-343, a pyridone-containing S-adenosyl-L-methionine cofactor-competitive EZH2 inhibitor that is representative of its class, and HKMTI-1-005, a substrate-competitive dual inhibitor targeting EZH2 and the closely related G9A/GLP H3K9 methyltransferases. We found that treatment with HKMTI-1-005 phenocopied EZH2 knockdown and was more effective in inducing differentiation than GSK-343, despite the efficacy of GSK-343 in terms of abolishing H3K27 trimethylation. Furthermore, transcriptomic analysis revealed that in contrast to treatment with GSK-343, HKMTI-1-005 upregulated the expression of differentiation pathway genes with and without ATRA, while downregulating genes associated with a hematopoietic stem cell phenotype. These results pointed to a non-canonical role for EZH2, which was supported by the finding that EZH2 associates with the master regulator of myeloid differentiation, RARα, in an ATRA-dependent manner that was enhanced by HKMTI-1-005, possibly playing a role in co-regulator complex exchange during transcriptional activation. In summary, our results strongly suggest that addition of HKMTI-1-005 to ATRA is a new therapeutic approach against AML that warrants further investigation.

Differing perceptions of intervention thresholds for fracture risk: a survey of patients and doctors.

UNLABELLED: This survey suggests that patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy. INTRODUCTION: Absolute fracture risk estimates are now incorporated into osteoporosis treatment guidelines. At present, little is known about how patients regard fracture risk and its management. We set out to describe and compare the views of patients and doctors on the level of fracture risk at which drug treatment is justified. METHODS: A cross-sectional survey was conducted on 114 patients referred for bone density measurement and 161 doctors whose practice includes management of osteoporosis. Participants were asked about fracture risk thresholds for pharmacological intervention. RESULTS: The absolute risk of both major osteoporotic fracture and hip fracture at which drug treatment was considered by patients to be justifiable was higher than that reported by doctors [major osteoporotic fracture, median (interquartile range): patients, 50% (25 to 60); doctors, 10% (10 to 20); P < 0.0001; hip fracture: patients, 50% (25 to 60); doctors, 10% (5 to 20); P < 0.0001]. Patients required that a drug provide a median 50% reduction in relative risk of fracture in order to consider taking long-term therapy, irrespective of the treatment mode or dosing schedule. Among doctors, there was an inverse relationship between the number of osteoporosis consultations conducted each month and threshold of risk for recommending drug treatment (r = -0.22 and r = -0.29 for major osteoporotic fracture and hip fracture, respectively, P < 0.01 for both) CONCLUSIONS: Patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy.

The effect of dietary concentrate and soya oil inclusion on microbial diversity in the rumen of cattle.

AIMS: Methane emissions from ruminants are a significant contributor to global greenhouse gas production. The aim of this study was to examine the effect of diet on microbial communities in the rumen of steers. METHODS AND RESULTS: The effects of dietary alteration (50 : 50 vs 90 : 10 concentrate-forage ratio, and inclusion of soya oil) on methanogenic and bacterial communities in the rumen of steers were examined using molecular fingerprinting techniques (T-RFLP and automated ribosomal intergenic spacer analysis) and real-time PCR. Bacterial diversity was greatly affected by diet, whereas methanogen diversity was not. However, methanogen abundance was significantly reduced (P = 0.009) in high concentrate-forage diets and in the presence of soya oil (6%). In a parallel study, reduced methane emissions were observed with these diets. CONCLUSIONS: The greater effect of dietary alteration on bacterial community in the rumen compared with the methanogen community may reflect the impact of substrate availability on the rumen bacterial community. This resulted in altered rumen volatile fatty acid profiles and had a downstream effect on methanogen abundance, but not diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding how rumen microbial communities contribute to methane production and how these microbes are influenced by diet is essential for the rational design of methane mitigation strategies from livestock.

An investigation into the effects of social evaluation on cardiovascular and endocrine responses to the CO2 stress test in humans.

The present study examined whether social evaluation could heighten individuals' physiological responses to the CO(2) stress test, and the hypothalamic-pituitary-adrenal (HPA) response in particular. Twenty-five healthy volunteers undertook the CO(2) test under three conditions: (i) standard CO(2) protocol, (ii) standard CO(2) protocol conducted in front of a full-length mirror (mirror) and (iii) standard CO(2) protocol conducted in front of a video camera deemed to be transmitting live images of the procedure to investigators evaluating participant performance (video). Despite counterbalancing for task order, there were significant differences in anger and depression among the conditions. Repeated measures analysis of variances (ANOVAs), controlling for these mood indices, revealed that salivary cortisol, heart rate and systolic blood pressure responses to the CO(2) test were not affected by social evaluation (i.e. mirror or video). Although the data provide no evidence that endocrine and cardiovascular responses to the CO(2) test are affected by social evaluation, the potency of the social evaluation manipulation in this study is in question. Thus, further research is warranted which includes evidence of, or instructions suggesting negative social evaluation.

Histone deacetylase inhibitors in APL and beyond.

In recent years the study of chemical modifications to chromatin and their effects on cellular processes has become increasingly important in the field of cancer research. Disruptions to the normal epigenetic pattern of the cell can serve as biomarkers and are important determinants of cancer progression. Accordingly, drugs that inhibit the enzymes responsible for modulating these epigenetic markers, in particular histone deacetylases, are the focus of intense research and development. In this chapter we provide an overview of class I and II histone deacetylases as well as a guide to the diverse types of histone deacetylase inhibitors and their activities in the context of APL. We also discuss the rationale for the use of histone deacetylase inhibitors in combination therapy for the treatment of cancer and the current status of clinical trials.

Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia.

We showed previously that net secretory output of apolipoprotein B (apo B) from cultured human hepatoma cells (HepG2) is regulated by rapid reuptake of nascent lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent lipoproteins could be remodeled to enhance or impede reuptake. We found that lipoprotein lipase (LpL), an enzyme that hydrolyzes lipoprotein triglyceride, reduced HepG2 output of apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short as 2 h and as long as 24 h. Heparin, which blocks receptor-mediated binding of lipoproteins, abolished the effect of LpL on apo B output, without causing enzyme inhibition. To assess uptake directly, we prepared labeled nascent lipoproteins. LpL tripled the cellular uptake of labeled nascent lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I-labeled anti-LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and familial combined hyperlipidemia.

Patients with acute myocardial infarction have an inaccurate understanding of their risk of a future cardiac event.

BACKGROUND: Accurate perceptions of future cardiac risk are important to ensure informed treatment choices and lifestyle adaptation in patients following myocardial infarction (MI). The aim of this study was to investigate whether risk perceptions of patients with MI were accurate compared with an established clinical risk model. METHODS: Seventy-nine consecutive patients with acute MI admitted to the Coronary Care Unit, Auckland Hospital, completed a questionnaire assessing risk perceptions. Clinical data were used to calculate patients' Thrombolysis In Myocardial Infarction (TIMI) risk scores, a validated predictive model of prognosis. The main outcome measures were the associations between perceived risk, TIMI risk scores and troponin T. RESULTS: Patients' risk perceptions showed no correlation with thrombolysis in myocardial infarction risk scores (r = -0.06; P = 0.61) or with troponin T (r = -0.07; P = 0.53). Patients' risk perceptions were not significantly associated with age or sex, and were not significantly higher in those who had experienced a previous MI, a family history of coronary heart disease, diabetes or smokers. Higher perceived risk was significantly associated with a number of illness perceptions, including worse consequences of the MI and lower beliefs in the benefit of treatment. Patients who overestimated their risk were more anxious than other patients (F(2, 73) = 22.97; P = 0.0001). CONCLUSION: Patients with MI ideas about their personal risk of future MI are not congruent with their clinical risk assessments. Inpatient hospital care appears to be unsuccessful in communicating prognosis effectively to patients. Improving the accuracy of risk perceptions may help decrease unnecessary cardiac anxiety and invalidism in some patients and prompt risk-reducing behaviours in others.

Modern health worries in medical students.

OBJECTIVE: The aim of this study was to investigate the association between modern health worries (MHW), subjective health complaints, and use of health care services in first-year Dutch medical students, and to compare MHW in Dutch and New Zealand cohorts. METHODS: Two hundred and twenty-seven Dutch first-year medical students completed questionnaires assessing MHW, subjective health complaints, positive and negative affect (PA and NA, respectively), and use of health care services. RESULTS: Dutch medical students were most concerned about drug resistant bacteria and least concerned about vaccination programmes. Overall, female students were more concerned about modern health issues than were male students. Students' scores on the MHW scale were significantly associated with subjective health complaints. Subjective health complaints were also significantly related to the use of health care services. The factor structure of the MHW scale was replicated. Respondents reported significantly lower scores on all MHW items than did New Zealand students. CONCLUSIONS: Worries about modernity are reliably associated with subjective health complaints and use of health care services in Dutch medical students.

A double-blind trial of melatonin as a treatment for jet lag in international cabin crew.

This study investigated the efficacy of oral melatonin in alleviating jet lag in flight crew after a series of international flights. The optimal time for taking melatonin in this group was also investigated. In a double-blind placebo-controlled trial, 52 international cabin crew were randomly assigned to three groups; early melatonin (5 mg started 3 days prior to arrival until 5 days after return home); late melatonin (placebo for 3 days then 5 mg melatonin for 5 days); and placebo. Daily ratings showed a trend in jet lag, mood, and sleepiness measures toward an improved recovery in the late melatonin group and a worse recovery in the early melatonin group as compared to placebo. Retrospective ratings made 6 days after arrival showed the late melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness than the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin may have potential benefits for international aircrew.

Clustering of attempted suicide: New Zealand national data.

BACKGROUND: The extent to which clusters of attempted suicides occur is a significant problem that is complementary to the current available research on the clustering of completed suicide. However, little systematic research on clusters of attempted suicides exists. The present study examines the extent and nature of clustering of suicide attempts. METHOD: The occurrence of clustering of attempted suicide was examined in nationwide data for all New Zealand hospitals, obtained from the New Zealand Health Statistics Services for the years 1988-1990. The Scan statistic and Knox procedure were employed for testing the significance of clusters in time and time-space, respectively. RESULTS: The analyses indicated that significant time clustering occurred in younger age groups, specifically among 15-19 and 20-24 year olds. The results could not be accounted for by seasonal variations in admissions. Age specificity of time-space clusters emerged, exhibiting a similar pattern to that reported for completed suicides in the US. CONCLUSIONS: The results suggest a similar underlying mechanism for the clustering of parasuicide and completed suicides and provide support for the existence of contagion of suicidal behaviour. The implications for prevention are discussed.

Disclosure of trauma and immune response to a hepatitis B vaccination program.

This study investigated whether emotional expression of traumatic experiences influenced the immune response to a hepatitis B vaccination program. Forty medical students who tested negative for hepatitis B antibodies were randomly assigned to write about personal traumatic events or control topics during 4 consecutive daily sessions. The day after completion of the writing, participants were given their first hepatitis B vaccination, with booster injections at 1 and 4 months after the writing. Blood was collected before each vaccination and at a 6-month follow-up. Compared with the control group, participants in the emotional expression group showed significantly higher antibody levels against hepatitis B at the 4 and 6-month follow-up periods. Other immune changes evident immediately after writing were significantly lower numbers of circulating T helper lymphocytes and basophils in the treatment group. The finding that a writing intervention influences immune response provides further support for a link between emotional disclosure and health.

Health-promoting variables as predictors of response to a brief pain management program.

This study investigated the value of the sense of coherence (SOC), self-esteem, and the Mental Health Inventory subscales as predictors of response to a brief pain management program. One hundred and seven chronic pain patients who participated in a pain management program, which included education about pain, relaxation training, and stress management, were sent a follow-up questionnaire 6 months after the course. Reported pain intensity since the course was significantly associated with SOC subscale meaningfulness. The use of relaxation and other techniques taught in the course was correlated with positive affect and well-being. The results suggest that health-promoting variables may offer advantages over pathological measures as predictors of patient response to pain management programs, and SOC is worthy of further study.

The immunological effects of thought suppression.

Individuals often suppress emotional thoughts, particularly thoughts that arouse negative emotions, as a way of regulating mood and reducing distress. However, recent work has highlighted the complexities and unexpected cognitive and physiological effects of thought suppression. In a study designed to examine the short-term immunological effects of thought suppression, participants wrote about either emotional or nonemotional topics with or without thought suppression. Blood was drawn before and after each experimental session on 3 consecutive days. Results showed a significant increase in circulating total lymphocytes and CD4 (helper) T lymphocyte levels in the emotional writing groups. Thought suppression resulted in a significant decrease in CD3 T lymphocyte levels. The implications of the results for the role of the expression and suppression of emotion in health are discussed.

Adolescent perceptions of smoking imagery in film.

Smoking amongst adolescents in New Zealand continues to be a problem, with more than a one-third increase in smoking prevalence between 1992 and 1997. Favourable portrayals of smoking in the media have been cited as potential motivators of the initiation of smoking among adolescents. To date, however, its role in influencing smoking perceptions and behaviours has not received systematic analysis. A qualitative study was conducted to explore how adolescents interpret and decode smoking imagery in movies. Data was collected through focus groups. Same-gender groups of 12- and 13-year-old students were interviewed at their schools. Participants discussed their recollections of and responses to portrayals of smoking in recently viewed films, as well as their perceptions of smoking in general. Students perceived that smoking in film is both highly prevalent and recognisable, and they regarded on-screen-smoking imagery as an accurate reflection of reality. Adolescents in this study were predominantly nonchalant towards the inclusion of smoking images in film, and they perceived an unrealistically high prevalence of smoking amongst peers and adults. Their noncholant response is linked with the perception that smoking is normal and prevalent and with the broad understanding of the constructed nature of media imagery. Smoking imagery in film may play a critical role in reinforcing cultural interpretations of tobacco use, such as its role as a means of stress relief, development of self-image and as a marker of adult independence.