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Competing Interests: DS is an expert advisor to the National Institutes of Clinical Excellence (NICE, UK) Centre for Guidelines. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objective: Type 2 diabetes (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin, which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin use with incident dementia and cognitive decline over 6 years in participants with diabetes compared with those not receiving metformin and those without diabetes., Research Design and Methods: A prospective observational study was conducted of N = 1,037 community-dwelling older participants without dementia aged 70-90 years at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease, or progressive malignancy. Neuropsychological testing measured cognitive function every 2 years; a battery of tests measured executive function, memory, attention/speed, language, and visuospatial function individually. These were used to determine the measure of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal, and parahippocampal volumes were measured by MRI at baseline and 2 years ( n = 526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, BMI, heart disease, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage., Results: Of n = 1,037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those who did not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared with DM-noMF. Incident dementia was significantly higher in DM-noMF compared with DM+MF (odds ratio 5.29 [95% CI 1.17-23.88]; P = 0.05)., Conclusions: Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin., (© 2020 by the American Diabetes Association.)

Objective: Graves' disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRAbs) are clearly pathogenic, but the role of thyroidperoxidase antibodies (TPOAbs) in Graves disease is unknown., Methods: We retrospectively studied whether TPOAb positivity reduced risk of relapse following antithyroid drug (ATD) treatment in newly diagnosed Graves disease., Results: During follow-up of 204 patients with TRAb-positive Graves disease, 107 (52%) relapsed following withdrawal of ATD. Mean age was 40.0 years, and 82% were female. The average duration of ATD treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAbs significantly increased risk of Graves relapse (odds ratio, 2.21). Male sex and younger age were other factors significantly associated with increased risk of relapse., Conclusion: TPOAb positivity significantly improves the odds of remission following ATD treatment in newly diagnosed Graves' disease., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

We assessed the value of the Edmonton Obesity Staging System (EOSS) compared with the body mass index (BMI) for determining associations with use of health services and pharmacotherapies in a nationally representative sample of participants in the 2011-2013 Australian Health Survey. A subsample of participants aged 18 years or over, with at least overweight (BMI ≥ 25 kg/m 2 ) or central obesity (waist measurement of ≥102 cm for men; ≥88 cm for women), and who had provided physical measurements (n = 9730) were selected for analysis. For statistical significance of each predictor, we used logistic regression for model comparisons with the BMI and EOSS separately, and adjusted for covariates. For relative explanatory ability, we used the Nagelkerke pseudo R 2 , receiver operating characteristic curve, and area under curve statistic. The EOSS was significantly better than the BMI for predicting polypharmacy and most of the health service use variables. Conversely, the BMI was significantly better than the EOSS for predicting having discussed lifestyle changes relevant to weight loss with the primary care physician. Clinicians, health care professionals, consumers, and policy makers should consider the EOSS a more accurate predictor of polypharmacy and health service use than the BMI in adults with overweight or obesity., (© 2020 World Obesity Federation.)

Objectives: Infections caused by dermatophytes affect a high percentage of the population. Antifungal susceptibility testing (AST) can offer useful information about the susceptibility profiles of the pathogens as well as the concomitant documentation of the appropriate treatment. However, the slow growth rate of these fungi and their poor sporulation are factors that can delay and affect the performance of the AST. The proposed methods by the CLSI or the EUCAST are both laborious for the everyday routine. There are alternative applications which propose the use of an inoculum, consisting of a conidia-mycelium mixture or even plain mycelia, as well as the use of resazurin in order to facilitate the reading. The aim of this study was to compare these approaches to the EUCAST method and evaluate their performance., Methods: Three alternative methods were compared to the EUCAST proposed methodology for conidia forming molds. The last was defined as the reference method. The methods under evaluation were (a) a fragmented mycelia method, (b) the EUCAST method with the addition of resazurin sodium salt solution and (c) the fragmented mycelia method with the addition of resazurin sodium salt solution. Twenty-two isolates (8 Trichophyton interdigitale , 8 T. rubrum , and 6 Microsporum canis ) were tested against the antifungal agents of griseofulvin, terbinafine, fluconazole, and itraconazole., Results: The essential agreement between the methods was calculated in percentages and a statistical analysis of the results was performed. Data evaluation revealed sufficient overall agreement of the methods with the addition of resazurin to the initial "uncolored" methods (98.9 and 97.5% for the EUCAST and the fragmented mycelia methods, respectively). The fragmented mycelia method exhibited a relatively sufficient overall agreement in comparison to the EUCAST method (90%) and not a satisfactory correlation, probably as a result of various issues of standardization., Conclusion: The EUCAST method was found to be the more reliable one, whereas the addition of resazurin sodium salt solution facilitates the reading and provides a reliable and objective evaluation. The fragmented mycelia method could serve as an alternative that should be applied only in cases of poor or no sporulating dermatophytes., (Copyright © 2020 Markantonatou, Samaras, Zachrou and Vyzantiadis.)

Background and Purpose- Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods- Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1-6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results- Patients with T2D had significantly poorer performance in global cognition (SD, -0.59 [95% CI, -0.82 to -0.36]; P <0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, -0.10 [95% CI, -0.45 to 0.24]; P =0.55) or in any cognitive domain. Conclusions- Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.

Background: There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline., Objectives: This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Interactions between statin use and known dementia risk factors were examined., Methods: Prospective observational study of community-dwelling elderly Australians age 70 to 90 years (the MAS [Sydney Memory and Ageing Study], n = 1,037). Outcome measures were memory and global cognition (by neuropsychological testing every 2 years) and total brain, hippocampal and parahippocampal volumes (by magnetic resonance) in a subgroup (n = 526). Analyses applied linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage. Interactions were sought between statin use and dementia risk factors., Results: Over 6 years there was no difference in the rate of decline in memory or global cognition between statin users and never users. Statin initiation during the observation period was associated with blunting the rate of memory decline. Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Eε4 carriage. There was no difference in brain volume changes between statin users and never users., Conclusions: In community-dwelling elderly Australians, statin therapy was not associated with any greater decline in memory or cognition over 6 years. These data are reassuring for consumers concerned about statin use and risk of memory decline., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Saksenaea vasiformis is an emerging human pathogen, belonging to the order Mucorales of the subphylum Mucormycotina, most often associated with rhino-cerebral, cutaneous and subcutaneous infections following trauma. A review of the published literature was attempted on the occasion of a cutaneous leg infection with favorable outcome in a young immunocompetent man after mild injury. The overall aim was the facilitation of the study and the integrated understanding of this kind of fungal infections., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Adipocytes support key metabolic and endocrine functions of adipose tissue. Lipid is stored in two major classes of depots, namely visceral adipose (VA) and subcutaneous adipose (SA) depots. Increased visceral adiposity is associated with adverse health outcomes, whereas the impact of SA tissue is relatively metabolically benign. The precise molecular features associated with the functional differences between the adipose depots are still not well understood. Here, we characterised transcriptomes and methylomes of isolated adipocytes from matched SA and VA tissues of individuals with normal BMI to identify epigenetic differences and their contribution to cell type and depot-specific function. We found that DNA methylomes were notably distinct between different adipocyte depots and were associated with differential gene expression within pathways fundamental to adipocyte function. Most striking differential methylation was found at transcription factor and developmental genes. Our findings highlight the importance of developmental origins in the function of different fat depots.

Background: Severe mental illness (SMI) is thought to be associated with lower diet quality and adverse eating behaviours contributing towards physical health disparities. A rigorous review of the studies looking at dietary intake in psychotic disorders and bipolar disorder is lacking.AimsTo conduct a systematic, comprehensive evaluation of the published research on dietary intake in psychotic disorders and bipolar disorder., Method: Six electronic databases were searched for studies reporting on dietary intakes in psychotic disorders and bipolar disorder. Dietary-assessment methods, and dietary intakes, were systematically reviewed. Where possible, data was pooled for meta-analysis and compared with healthy controls., Results: In total, 58 eligible studies were identified. People with SMI were found to have significantly higher dietary energy (mean difference 1332 kJ, 95% CI 487-2178 kJ/day, P = 0.002, g = 0.463) and sodium (mean difference 322 mg, 95% CI 174-490 mg, P &lt; 0.001, g = 0.414) intake compared with controls. Qualitative synthesis suggested that higher energy and sodium intakes were associated with poorer diet quality and eating patterns., Conclusions: These dietary components should be key targets for preventative interventions to improve weight and other physical health outcomes in people with SMI.Declaration of interestS.B.T. and E.T. have clinical dietitian appointments within the South Eastern Sydney Local Health District and do not receive any further funding.

Aspergillus galactomannan immunoassay is a main diagnostic and monitoring tool in medical mycology. However, the specificity of the method can be skewered by the presence of several other fungi. Trying to diagnose a possible fungal infection of the lower respiratory tract in a haematology patient, it appeared that the fungus Trichoderma longibrachiatum is an additional probable cause of positive galactomannan results. Although, that Trichoderma is a rare but emerging pathogen in immunocompromised patients, the above information could be a caution point in the clinical evaluation of diagnostic results.

Introduction: Antipsychotic medication (APM) initiation is associated with rapid and substantial weight-gain and high rates of obesity. Obesity leads to premature onset of cardiometabolic diseases and contributes to the 15-20 year shortfall in life expectancy in those experiencing severe mental illness. Dietary energy intake excess is critical to weight management but is yet to be quantified in youth with first episode psychosis (FEP) receiving APM. This study aimed to describe the degree of energy overconsumption and the food sources contributing to this in youth with FEP. Materials and Methods: People aged 15-30 years with FEP receiving APM completed diet histories through qualified dietitians to assess energy imbalance and food sources. Outcome measures were: (i) energy balance; and (ii) intake of core and discretionary foods. Results: Participants ( n = 93) were aged 15-29 years (mean = 21.4 ± 2.9 years) and exposed to APMs for a median for 8 months (Interquartile Range (IQR) 11 months). Energy balance was exceeded by 26%, by a median 1,837 kJ per day (IQR 5,365 kJ). APM polypharmacy and olanzapine were linked to larger excesses in dietary energy intake. The greatest contributors to energy intake were refined grain foods (33%) and discretionary foods (31%). Conclusion: Young people with FEP receiving APMs appear to have markedly excessive energy consumption, likely contributing to rapid weight-gain, and thereby seeding future poor physical health. Larger, prospective studies are needed to gain a greater understanding of dietary intake, and its effects on health, in people with FEP.

Since the introduction of combined antiretroviral therapy (cART) and more effective treatments for AIDS, there has been a dramatic shift from the weight loss and wasting that characterised HIV/AIDS (and still does in countries where cART is not readily available or is initiated late) to healthy weight, or even overweight and obesity at rates mirroring those seen in the general population. These trends are attributable to several factors, including the " return to health " weight gain with reversal of the catabolic effects of HIV-infection following cART-initiation, strategies for earlier cART-initiation in the course of HIV-infection which have prevented many people living with HIV-infection from developing wasting, in addition to exposure to the modern obesogenic environment. Older cART regimens were associated with increased risk of body fat partitioning disorders (lipodystrophy) and cardiometabolic complications including atherothrombotic cardiovascular disease (CVD) and diabetes mellitus. Whilst cART now avoids those medications implicated in causing lipodystrophy, long-term cardiometabolic data on more modern cART regimens are lacking. Longitudinal studies show increased rates of incident CVD and diabetes mellitus with weight gain in treated HIV-infection. Abdominal fat gain, weight gain, and rising body mass index (BMI) in the short-term during HIV treatment was found to increase incident diabetes risk. Rising BMI was associated with increased risk of incident CVD, however the relationship varied depending on pre-cART BMI category. In contrast, a protective association with mortality is evident, predominantly in the underweight and in resource-poor settings, where weight gain reflects access to cART and virological suppression. The question of how to best evaluate, manage (and perhaps constrain) weight gain during HIV treatment is of clinical relevance, especially in the current climate of increasingly widespread cART use, rising overweight, and obesity prevalence and growing metabolic and cardiovascular disease burden in people living with HIV-infection. Large prospective studies to further characterise the relationship between weight gain during HIV treatment and risk of diabetes, CVD and mortality are required.

Treated human immunodeficiency virus (HIV) infection is associated with high rates of type 2 diabetes mellitus (DM), metabolic syndrome and central obesity/body fat partitioning disorders. To our knowledge, there are no available data comparing diabetes care in people with both HIV+DM vs. DM alone (DM-controls) within the same service and evaluating if benchmarked standards of care are being met in people with HIV+DM. This study evaluated the frequency that people with HIV+DM met the benchmarked American Diabetes Association (ADA) standards of care in diabetes (targets for HbA1c, blood pressure, lipid levels, complication screening, and healthy weight), compared to age- and sex- matched controls with diabetes, in an urban teaching hospital. The frequency of diabetes complications and rates of obesity and metabolic syndrome were also examined. All participants were male; individuals with HIV+DM ( n = 30) were similar to DM-controls ( n = 30) for age, diabetes duration and smoking status, but were more frequently non-obese compared to DM controls (92 vs. 55%, respectively, p = 0.003). Only 41% of HIV+DM met HbA1c targets, compared with 70% of DM-controls ( p = 0.037). Blood pressure targets were poorly met in both HIV+DM and DM-controls: 43 vs. 23%, respectively ( p = 0.12); LDL cholesterol targets were met in 65 vs. 67% ( p = 1.0). Benchmarked complication screening rates were similar between HIV+DM vs. DM-controls for annual foot examination (53 vs. 67%, respectively, p = 0.29); biennial retinal examination (83 vs. 77%, respectively, p = 0.52); and annual urinary albumin measurement (77 vs. 67%, respectively, p = 0.39). The prevalence of diabetes complications was similar between HIV+DM compared to DM-controls: macrovascular complications were present in 23% in both groups ( p = 1.0); the prevalence of microvascular complications was 40 vs. 30%, respectively ( p = 0.51). Achieving the standard of care benchmarks for diabetes in people with both HIV-infection and diabetes is of particular importance to mitigate against the accelerated cardiometabolic outcomes observed in those with treated HIV infection. HIV+DM were less likely to achieve HbA1c targets than people with diabetes, but without HIV. People with HIV+DM may require specific strategies to ensure care benchmarks are met.

Objectives: While obesity has been linked with lower quality of life in the general adult population, the prospective effects of present obesity on future quality of life amongst the elderly is unclear. This article investigates the cross-sectional and longitudinal relationships between obesity and aspects of quality of life in community-dwelling older Australians., Method: A 2-year longitudinal sample of community dwellers aged 70-90 years at baseline, derived from the Sydney Memory and Ageing Study (MAS), was chosen for the study. Of the 1037 participants in the original MAS sample, a baseline (Wave 1) sample of 926 and a 2-year follow-up (Wave 2) sample of 751 subjects were retained for these analyses. Adiposity was measured using body mass index (BMI) and waist circumference (WC). Quality of life was measured using the Assessment of Quality of Life (6 dimensions) questionnaire (AQoL-6D) as well as the Satisfaction with Life Scale (SWLS). Linear regression and analysis of covariance (ANCOVA) were used to examine linear and non-linear relationships between BMI and WC and measures of health-related quality of life (HRQoL) and satisfaction with life, adjusting for age, sex, education, asthma, osteoporosis, depression, hearing and visual impairment, mild cognitive impairment, physical activity, and general health. Where a non-linear relationship was found, established BMI or WC categories were used in ANCOVA., Results: Greater adiposity was associated with lower HRQoL but not life satisfaction. Regression modelling in cross-sectional analyses showed that higher BMI and greater WC were associated with lower scores for independent living, relationships, and pain (i.e. worse pain) on the AQoL-6D. In planned contrasts within a series of univariate analyses, obese participants scored lower in independent living and relationships, compared to normal weight and overweight participants. Longitudinal analyses found that higher baseline BMI and WC were associated with lower independent living scores at Wave 2., Conclusions: Obesity is associated with and predicts lower quality of life in elderly adults aged 70-90 years, and the areas most affected are independent living, social relationships, and the experience of pain.

Background: Amiodarone-induced thyrotoxicosis (AIT) is associated with significant morbidity and mortality, particularly in patients with cardiac failure. The aim of the study was to evaluate the management of AIT at a tertiary hospital specialising in cardiac failure and transplantation. Methods: Retrospective audit of 66 patients treated for AIT by Endocrinology (2007-2016), classified as type 1 (T1) or type 2 (T2) based on radiological criteria. Main outcome measurements were response rate to initial treatment, time to euthyroidism, and frequency/safety of thyroidectomy. Results: Mean age was 60 ± 2 years; 80% were male. Sixty-four patients commenced medical treatment: thionamides (THIO) in 23, glucocorticoids (GC) in 17 and combination (COMB) in 24. Median thyroxine (fT4) was 35.1 (31.2-46.7) in THIO, 43.1 (30.4 -60.7) in GC, and 60.0 (39.0 ->99.9) pmol/L in COMB ( p = 0.01). Initial therapy induced euthyroidism in 52%: 70% THIO, 53% GC, and 33% COMB ( p = 0.045) by 100 (49-167), 47 (35-61), and 53 (45-99) days, respectively ( p = 0.02). A further 11% became euthyroid after transitioning from monotherapy to COMB. Thyroidectomy was undertaken in 33%. Patients who underwent thyroidectomy were younger (54 ± 3 vs. 63 ± 2 years; p = 0.03), with higher prevalence of severely impaired left ventricular function prior to diagnosis of AIT (38 vs. 18%; p = 0.08). Despite median American Society of Anaesthesiologists classification 4, no thyroidectomy patient experienced cardiorespiratory complications/death. Conclusions: Patients with AIT had limited response to medical treatment. The poorest response was observed in COMB group, likely related to greater hyperthyroidism severity. Thyroidectomy is safe in patients with severe cardiac failure if performed in a centre with cardiac anaesthetic expertise. There should be low threshold for proceeding to thyroidectomy in patients with severe AIT and/or cardiac failure.

We aimed to describe the current state of specialist obesity services for adults with clinically severe obesity in public hospitals in Australia, and to analyse the gap in resources based on expert consensus. We conducted two surveys to collect information about current and required specialist obesity services and resources using open-ended questionnaires. Organizational level data were sought from clinician expert representatives of specialist obesity services across Australia in 2017. Fifteen of 16 representatives of current services in New South Wales (n = 8), Queensland (n = 1), Victoria (n = 2), South Australia (n = 3), and the Australian Capital Territory (n = 1) provided data. The composition of services varied substantially between hospitals, and patient access to services and effective treatments were limited by strict entry criteria (e.g. body mass index 40 kg/m 2 or higher with specific complication/s), prolonged wait times, geographical location (major cities only) and out-of-pocket costs. Of these services, 47% had a multidisciplinary team (MDT), 53% had an exercise physiologist/physiotherapist, 53% had a bariatric surgeon and 33% had pharmacotherapy resources. Key gaps included staffing components of the MDT (psychologist, exercise physiologist/physiotherapist) and access to publicly funded weight loss pharmacotherapy and bariatric surgery. There was consensus on the need for significant improvements in staff, physical infrastructure, access to services, education/training in obesity medicine and targeted research funding. Based on the small number of existing, often under-resourced specialist obesity services that are located only in a few major cities, the vast majority of Australians with clinically severe obesity cannot access the specialist evidence based treatments needed., (© 2018 World Obesity Federation.)

Objective: To determine the long-term incidence of glucose disorders in treated HIV infection, associations with traditional and HIV-specific risk factors., Methods: Observational cohort of 104 men with treated HIV infection and without diabetes, aged 43 ± 8 years at baseline, with (mean ± SD) 11.8 ± 3.5 years follow-up. Ascertainment of glucose status by fasting glucose or, in a subset (n = 33), a 75 g oral glucose tolerance test by 10-12 years follow-up. A subset underwent sequential body composition measures (n = 58) to determine changes in total body and central abdominal adiposity., Results: The cumulative incidence of glucose disorders was 48.1% (prediabetes 35.6%, diabetes 12.5%), with an incidence rate of 34.5/1000 years of patient follow-up (PYFU) (prediabetes: 24.3/1000 PYFU; diabetes: 10.2/1000 PYFU). Incident glucose disorders were independently associated with higher age (44.9 ± 8.4 vs. 41.1 ± 7.5 years, P = 0.027), baseline C-peptide (2.9 ± 1.3 vs. 2.4 ± 1.1 ng/ml, P = 0.019) and baseline 2-h glucose (135 ± 41 vs. 95 ± 25 mg/dl, P < 0.001). A prior AIDS-defining illness was independently associated with higher follow-up fasting glucose (108 ± 38 vs. 94 ± 16 mg/dl, P = 0.007). Abdominal fat gain over 2-4 years was associated with a 3.16-fold increased risk of incident glucose disorders (95% CI 1.30-7.68, P = 0.011). In a subgroup who underwent further oral glucose tolerance testing, 60% had a glucose disorder, the majority not detected by fasting glucose., Conclusion: Men with long-term treated HIV infection have high rates of incident glucose disorders associated with modest abdominal fat gain. Directed measures to prevent diabetes in this population are warranted.

People experiencing a severe mental illness (SMI), such as schizophrenia, schizoaffective disorder, bipolar affective disorder or depression with psychotic features, have a 20-year mortality gap compared to the general population. This 'scandal of premature mortality' is primarily driven by preventable cardiometabolic disease, and recent research suggests that the mortality gap is widening. Multidisciplinary mental health teams often include psychiatrists, clinical psychologists, specialist mental health nurses, social workers and occupational therapists, offering a range of pharmacological and nonpharmacological treatments to enhance the recovery of clients who have experienced, or are experiencing a SMI. Until recently, lifestyle and life skills interventions targeting the poor physical health experienced by people living with SMI have not been offered in most routine clinical settings. Furthermore, there are calls to include dietary intervention as mainstream in psychiatry to enhance mental health recovery. With the integration of dietitians being a relatively new approach, it is important to review and assess the literature to inform practice. This review assesses the dietary challenges experienced by people with a SMI and discusses potential strategies for improving mental and physical health., (© 2017 The British Dietetic Association Ltd.)

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion., (© 2017 Blackwell Verlag GmbH.)

Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1 , MSH2 , MSH6 , and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient's metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient's known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2 , suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Summary: Diamond-Blackfan anaemia (DBA) is a rare cause of bone marrow failure. The incidence of malignancy and endocrine complications are increased in DBA, relative to other inherited bone marrow failure syndromes. We describe an adult woman with DBA who developed osteoporosis and avascular necrosis (AVN) of both distal femora. Such endocrine complications are not uncommon in DBA, but under-appreciated, especially in adulthood. Further, rectal adenocarcinoma was diagnosed at age 32 years, requiring hemi-colectomy and adjuvant chemotherapy. Elevated cancer risk may warrant disease-specific screening guidelines. Genetic predictors of extra-haematopoetic complications in DBA are yet to be established., Learning Points: Endocrine complications are common in DBA.Clinical vigilance is required in managing bone health of DBA patients treated with glucocorticoids.There is currently no reliable way to predict which patients will develop complications of therapy or premature malignancy related to DBA.Complaints of bone or joint pain should prompt screening with targeted magnetic resonance imaging. Osteoporosis screening should be performed routinely.

Aim: Using routine hemoglobin A1c (HbA1c) testing to describe the prevalence, characteristics, and length of stay (LOS) of psychiatry inpatients with type 2 diabetes compared to those with pre-diabetes and those without diabetes., Methods: In this prospective observational study, all inpatients aged greater than 30 years admitted to the Austin Health Psychiatry Unit, a major tertiary hospital, affiliated with the University of Melbourne, between February 2014 and April 2015 had routine HbA1c testing as part of the Diabetes Discovery Initiative. Patients were divided into three groups: diabetes (HbA1c ≥ 6.5%, 48 mmol/mol), pre-diabetes (HbA1c 5.7-6.4%, 39-46 mmol/mol), or no diabetes (HbA1c ≤ 5.6%, 38 mmol/mol). Baseline characteristics, co-morbidities, psychiatric illnesses, and treatment were recorded., Results: There were a total of 335 psychiatry inpatients (median age 41 years). The most prevalent diagnoses were schizophrenia, depression, and substance abuse. Of the 335 psychiatric inpatients, 14% ( n  = 46) had diabetes and 19% ( n  = 63) had pre-diabetes, a prevalence threefold greater than in the aged matched general population. Compared to inpatients with pre-diabetes and no diabetes, those with diabetes were older and were at least twice as likely to have hypertension, obesity, and hyperlipidemia (all p  ≤ 0.002). In multivariable analyses, diabetes was associated with increasing age ( p  = 0.02), substance abuse ( p  = 0.04), dyslipidaemia ( p  = 0.03), and aripiprazole use ( p  = 0.01). Patients with diabetes also had a 70% longer expected LOS (95% CI: 20-130%; p  = 0.001), compared to those with pre-diabetes and no diabetes., Conclusion: Despite relative youth, one-third of all psychiatric inpatients above the age of 30 have diabetes or pre-diabetes. Presence of diabetes in psychiatric inpatients is associated with older age, substance abuse, and longer LOS. Routine inpatient HbA1c testing provides an opportunity for early detection and optimization of diabetes care.

Background: Nutrition interventions would appear fundamental for weight management and cardiometabolic risk reduction in people experiencing severe mental illness (SMI). Comprehensive evaluation of nutrition interventions is lacking., Aims: To subject randomised controlled trials of nutrition interventions in people with SMI to systematic review and meta-analysis, and to measure anthropometric and biochemical parameters and nutritional intake., Method: An electronic database search identified trials with nutrition intervention components. Trials were pooled for meta-analysis. Meta-regression analyses were performed on anthropometric moderators., Results: Interventions led to significant weight loss (19 studies), reduced body mass index (17 studies), decreased waist circumference (10 studies) and lower blood glucose levels (5 studies). Dietitian-led interventions (6 studies) and studies delivered at antipsychotic initiation (4 studies) had larger effect sizes., Conclusions: Evidence supports nutrition interventions as standard care in preventing and treating weight gain among people experiencing SMI., (© The Royal College of Psychiatrists 2017.)

Statin therapy has strong evidence supporting health benefits and mortality reduction in cardiovascular disease, stroke, diabetes, renal disease, and genetic lipid disorders. Further, reports that statin therapy might be protective against Alzheimer's disease have subsequently been refuted in randomized trials. Low-level evidence based on case reports suggests that statins may adversely affect memory, a significant consumer concern. In this review, the published evidence on statins and memory in the elderly in randomized controlled trials and prospective observational cohort studies was examined in detail. Overall, there was moderate-strength evidence that statin therapy did not increase the risk of dementia in the elderly and low-strength evidence for no increased risk for Alzheimer's disease. Further, there was moderate-strength evidence that statin therapy in the elderly did not increase the risk for mild cognitive impairment or worsen global cognitive performance in the cognitively intact or impaired. There was moderate-strength evidence for no deterioration of memory function in the elderly. On balance, there was a moderate level of evidence of neither harm nor benefit on memory; however, the published literature contains a number of deficiencies that are detailed in this review, not limited to selection biases and deficiencies of detailed testing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cardiometabolic morbidity is a significant contributor to the poorer health outcomes experienced by people with intellectual disability (ID). Tailoring cardiometabolic monitoring tools developed for the general population to better fit the altered risk profiles and extra needs of people with ID may help to improve health outcomes. This paper describes a new cardiometabolic monitoring framework designed to address the extra needs of people with ID. The framework was adapted from a generalist guideline after a process of extensive consultation with the original authors and over 30 ID and cardiometabolic experts. In addition to standard cardiometabolic monitoring practice, the framework encourages clinicians to: anticipate and address barriers to care such as communication difficulties and fear of blood tests; account for socioeconomic and genetic factors altering baseline cardiometabolic risk; and carefully rationalize psychotropic prescription. Together with this framework, a toolkit of free cardiometabolic resources tailored for people with ID and formal and informal carers is included. The monitoring framework promotes a multidisciplinary and holistic approach to cardiometabolic care for people with ID.

Aim: Initiating antipsychotic medication frequently induces rapid, clinically significant weight gain. We aimed to evaluate the effectiveness of a lifestyle and life skills intervention, delivered within 4 weeks of antipsychotic medication initiation, in attenuating weight gain in youth aged 14-25 years with first-episode psychosis (FEP)., Methods: We undertook a prospective, controlled study in two early psychosis community services. Intervention participants (n = 16) received a 12-week individualized intervention delivered by specialist clinical staff (nurse, dietician and exercise physiologist) and youth peer wellness coaches, in addition to standard care. A comparison group was recruited from a similar service and received standard care (n = 12)., Results: The intervention group experienced significantly less weight gain at 12 weeks compared to standard care (1.8 kg, 95% CI -0.4 to 2.8 vs. 7.8 kg, 4.8-10.7, P < 0.001). Thirteen per cent (2/16) of the intervention group experienced clinically significant weight gain (greater than 7% of baseline weight), while 75% (9/12) of the standard care group experienced this level of weight gain. Similar positive effects of the intervention were observed for waist circumference., Conclusions: A lifestyle and life skills intervention delivered as part of standard care attenuated antipsychotic-induced weight gain in young people with FEP. The intervention was acceptable to the young people referred to the service. Such interventions may prevent the seeding of future disease risk and in the long-term help reduce the life expectancy gap for people living with serious mental illness., (© 2015 Wiley Publishing Asia Pty Ltd.)

Severe mental illness is characterised by a 20-year mortality gap due to cardiometabolic disease. Poor diet in those with severe mental illness is an important and modifiable risk factor. The present study aimed to (i) examine baseline nutritional intake in youth with first-episode psychosis (FEP), (ii) evaluate the feasibility and acceptability of nutritional intervention early in FEP and (iii) to evaluate the effectiveness of early dietary intervention on key nutritional end points. Participants were recruited over a 12-month period from a community-based programme specifically targeting young people aged 15-25 years with newly diagnosed FEP. Individual dietetic consultations and practical group sessions were offered as part of a broader lifestyle programme. Dietary assessments were conducted before and at the end of the 12-week intervention. Participants exceeded recommended energy and Na intakes at baseline. Retention within the nutrition intervention was 67 %, consistent with other interventions offered to FEP clients. There was a 47 % reduction in discretionary food intake (-94 g/d, P<0·001) and reductions in daily energy (-24 %, P<0·001) and Na (-26 %, P<0·001) intakes. Diet quality significantly improved, and the mean change was 3·6 (95 % CI 0·2, 6·9, P<0·05), although this finding was not significant after Bonferroni's correction. Increased vegetable intake was the main factor contributing to improved diet quality. Nutrition intervention delivered shortly after initiation of antipsychotic medication is feasible, acceptable and effective in youth with FEP. Strategies to prevent weight gain and metabolic decline will contribute to prevent premature cardiometabolic disease in this vulnerable population.

Background: In patients with advanced heart failure, morbid obesity is a relative contraindication to heart transplantation due to higher morbidity and mortality in these patients., Methods: We performed a retrospective analysis of consecutive morbidly obese patients with advanced heart failure who underwent bariatric surgery for durable weight loss in order to meet eligibility criteria for cardiac transplantation., Results: Seven patients (4 M/3 F, age range 31-56 years) with left ventricular ejection fraction (LVEF) ≤ 25 % underwent laparoscopic bariatric surgery. Median preoperative body mass index (BMI) was 42.8 kg/m(2) (range 37.5-50.8). There were no major perioperative complications in six of seven patients. Median length of hospital stay was 5 days. There was no mortality recorded during complete patient follow-up. At a median follow-up of 406 days, median BMI reduction was 12.9 kg/m(2) (p = 0.017). Postoperative LVEF improved to a median of 30 % (interquartile range (IQR) 25-53 %; p = 0.039). Two patients underwent successful cardiac transplantation. Two patients reported symptomatic improvement with little change in LV function and now successfully meet listing criteria. Three patients showed marked improvement of their LVEF and functional status, thus removing the requirement for transplantation., Conclusions: Bariatric surgery can achieve successful weight loss in morbidly obese patients with advanced cardiac failure, enabling successful heart transplantation. In some patients, cardiac transplantation can be avoided through surgical weight loss.

Background: Iphiseius degenerans (Berlese) (Acari: Phytoseiidae) is a common predatory mite in citrus orchards in some areas of the Mediterranean basin and an important biological control agent of the thrips Frankliniella occidentalis (Pergande) in Integrated Pest Management (IPM) programmes in greenhouse crops. In this study, we evaluated the effects of the 'reduced-risk' insecticides acetamiprid, chlorantraniliprole, flubendiamide, metaflumizone, methoxyfenozide, spinetoram and thiamethoxam on I. degenerans, as a means of testing their compatibility in IPM programmes., Results: Although all pesticides decreased immature survival, high mortality was only recorded for young larvae when exposed to acetamiprid, while metaflumizone, thiamethoxam and spinetoram resulted in intermediate lethal effects. The estimated LC50 values of acetamiprid, spinetoram and thiamethoxam for I. degenerans females were 0.52, 0.84 and 0.16-fold lower than the respective maximum recommended doses of the pesticides for field application. Although all pesticides tested significantly decreased fecundity, highest rates corresponded to the three pesticides already mentioned., Conclusion: Chlorantraniliprole, flubendiamide and methoxyfenozide may preliminarily be included in IPM programmes, whereas the effects of acetamiprid, metaflumizone, spinetoram and thiamethoxam on I. degenerans should be clarified in further field toxicological tests. This information could be useful for rationally planning and implementing pest management on a sustainable basis., (© 2014 Society of Chemical Industry.)

Objectives: To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease., Design: Prospective observational study., Setting: Population-derived cohort., Participants: Individuals with a mean age of 78.6 ± 4.7 (N = 945)., Measurements: Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined., Results: IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer., Conclusion: IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Background: Triple therapy with pegylated interferon, ribavirin and a protease inhibitor has proven efficacy in hepatitis C infection and is currently the standard of care. Interferon-based therapies have been, rarely, associated with the development of Type 1 diabetes mellitus, but few cases have yet been reported in triple therapy for hepatitis C., Case Report: We describe a case of autoimmune Type 1 diabetes developing in a 23-year-old woman after initiation of triple therapy for chronic hepatitis C virus infection. The patient had the IL-28B gene polymorphism rs12979860 CT genotype, which is associated not only with antiviral therapy response but also with diabetes risk after liver transplantation for hepatitis C., Conclusion: Further studies are required to determine which individual characteristics may identify patients who are at risk of developing Type 1 diabetes when treated with interferon-based regimens for hepatitis C infection., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Individual dietetic consultations were trialled in a community-based first-episode psychosis program. Participants received eight individualised dietetic consultations, plus weekly shopping tours and cooking groups. The outcome measure was waist circumference (WC). In total, 30 patients commenced the program. An intention-to-treat analysis revealed, a statistically significant reduction in WC (mean=2.1±5.4 cm, t=2.1, df=29, p=0.04). Similar results were found for the 14 participants who attended all eight sessions (mean WC reduction=2.9±4.7 cm, t=2.3, df=13, p=0.04). Dietetic consultations were feasible and effective in reducing WC, and could enhance programs to reduce cardiometabolic risk in youth with psychosis using lifestyle interventions.

Foam sclerotherapy is a widely used method to treat varicose veins disease. It is easy to use and apply, affordable, and has high efficiency that depends on foam stability upon injection. Since sclerotherapy is usually applied in a medical doctor's office, one of the most employed methods to generate foam is based on the Tessari technique which uses pumping cycles of liquid and air in-and-out of a double syringe system. Finally, the produced foam exits through a small orifice (∼2mm) at the output of a three-way valve. The present work shows results regarding the factors that may influence foam stability (liquid to air ratio, type of connector, syringe diameter, number of pumping cycles, etc.) of a commonly used sclerosing agent (polidocanol). Furthermore, an effort is made to evaluate the effect of adding different substances on the stability of polidocanol foams (0.5% w/w) by altering the surface tension or/and the bulk and interfacial rheological properties of the fluids. It is shown that adding small concentrations of nonionic surfactants can increase foam stability with just a very small variation of the mean bubbles size., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The identification and characterisation of differentially methylated regions (DMRs) between phenotypes in the human genome is of prime interest in epigenetics. We present a novel method, DMRcate, that fits replicated methylation measurements from the Illumina HM450K BeadChip (or 450K array) spatially across the genome using a Gaussian kernel. DMRcate identifies and ranks the most differentially methylated regions across the genome based on tunable kernel smoothing of the differential methylation (DM) signal. The method is agnostic to both genomic annotation and local change in the direction of the DM signal, removes the bias incurred from irregularly spaced methylation sites, and assigns significance to each DMR called via comparison to a null model., Results: We show that, for both simulated and real data, the predictive performance of DMRcate is superior to those of Bumphunter and Probe Lasso, and commensurate with that of comb-p. For the real data, we validate all array-derived DMRs from the candidate methods on a suite of DMRs derived from whole-genome bisulfite sequencing called from the same DNA samples, using two separate phenotype comparisons., Conclusions: The agglomeration of genomically localised individual methylation sites into discrete DMRs is currently best served by a combination of DM-signal smoothing and subsequent threshold specification. The findings also suggest the design of the 450K array shows preference for CpG sites that are more likely to be differentially methylated, but its overall coverage does not adequately reflect the depth and complexity of methylation signatures afforded by sequencing. For the convenience of the research community we have created a user-friendly R software package called DMRcate, downloadable from Bioconductor and compatible with existing preprocessing packages, which allows others to apply the same DMR-finding method on 450K array data.

Adrenal masses are commonly found in the course of abdominal investigations and present diagnostic challenges. The foremost issue is whether the mass is the cause of the symptoms being investigated. Additional important clinical questions are: (1) is the adrenal mass benign or malignant and (2) whether the adrenal mass is functional or non-functional? We present a case of a 48-year-old man with severe abdominal pain. Imaging revealed a very large adrenal mass. Differential diagnostic procedures were performed and a diagnosis of primary adrenal lymphoma, an extremely rare cause of adrenal malignancy, was made. He proceeded to chemotherapy with cyclical cyclophosphamide, doxorubicin, etoposide and prednisolone, in addition to rituximab. This case illustrates the importance of establishing the nature of adrenal masses, to rapidly facilitate appropriate treatment., (2014 BMJ Publishing Group Ltd.)

Objectives: To determine whether obesity, estimated according to body mass index (BMI), waist circumference, and body fat and abdominal fat assessed using dual-energy X-ray absorptiometry (DEXA), was associated with cognitive performance., Design: Cross-sectional., Setting: Community based., Participants: Individuals aged 74-94 (N = 406)., Measurements: BMI, waist circumference, body fat, and abdominal fat were assessed using DEXA. Cognitive performance was assessed using a comprehensive neuropsychological battery., Results: When categorized using BMI, overweight individuals had higher global cognitive function and executive function scores than normal-weight individuals. This relationship did not differ according to sex. When categorized according to DEXA, there were no relationships between body fat and cognitive function in the whole group, but women in the middle and highest tertiles of DEXA body fat had better executive function than those in the lowest tertile. Men in the middle tertile of DEXA body fat had significantly better executive function and memory than those in the lowest tertile. BMI had greater power to predict executive function than DEXA body fat. No significant associations were found between cognition and estimates of abdominal adiposity., Conclusion: This study found an association between being overweight and better executive function in elderly adults; this association was stronger for the simpler BMI than the more-elaborate DEXA measures., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Importance: Presence of eating abnormalities is one of the core criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD), yet their occurrence in other subtypes of frontotemporal dementia (FTD) and effect on metabolic health is not known., Objective: To define and quantify patterns of eating behavior and energy, sugar, carbohydrate, protein, and fat intake, as well as indices of metabolic health in patients with bvFTD and semantic dementia (SD) compared with patients with Alzheimer disease (AD) and healthy control participants., Design, Setting, and Participants: Prospective case-controlled study involving patient and caregiver completion of surveys. Seventy-five participants with dementia (21 with bvFTD, 26 with SD, and 28 with AD) and 18 age- and education-matched healthy controls were recruited from FRONTIER, the FTD research clinic at Neuroscience Research Australia in Sydney., Main Outcomes and Measures: Caregivers of patients with FTD and AD completed validated questionnaires on appetite, eating behaviors, energy consumption, and dietary macronutrient composition. All participants completed surveys on hunger and satiety. Body mass index and weight measurements were prospectively collected., Results: The bvFTD group had significant abnormalities in the domains of appetite (U = 111.0, z = 2.7, P = .007), eating habits (U = 69.5, z = 3.8, P = .001), food preferences (U = 57.0, z = 4.1, P = .001), swallowing (U = 109.0, z = 3.0, P = .003), and other oral behaviors (U = 141.0, z = 2.6, P = .009) compared with the AD group. The bvFTD and SD groups tended to have increased energy consumption. Compared with controls, the bvFTD group had significantly increased carbohydrate intake (251 vs 170 g/d; P = .05) and the SD group had significantly increased sugar intake (114 vs 76 g/d; P = .049). No significant differences in total fat or protein intake between the groups were found. Despite similar energy intake, the SD group had lower hunger and satiety scores compared with the bvFTD group. In contrast, hunger and satiety scores did not differ between the bvFTD group and controls. The abnormal eating behavior was found in the 2 groups (bvFTD and SD) with the highest body mass index (F = 4.2, P = .008) and waist circumference (F = 6.4, P = .001)., Conclusions and Relevance: Abnormal eating behaviors are prominent in patients with bvFTD and those with SD and are not limited to increased appetite. The observed higher intake of sugar and carbohydrates was found in patients with the FTD subtypes and those with higher body mass index and waist circumference and was not explained simply by increased hunger or lower satiety.