Testosterone and the heart

The development of a subnormal level of testosterone (T) is not universal in ageing men, with 75% of men retaining normal levels. However, a substantial number of men do develop T deficiency (TD), with many of them carrying a portfolio of cardiovascular (CV) risk factors, including type 2 diabetes (T2D) and the metabolic syndrome. TD increases the risk of CV disease (CVD) and the risk of developing T2D and the metabolic syndrome. The key symptoms suggesting low T are sexual in nature, including erectile dysfunction (ED), loss of night-time erections and reduced libido. Many men with heart disease, if asked, admit to ED being present; a problem that is often compounded by drugs used to treat CVD. A large number of studies and meta-analyses have provided evidence of the link between TD and an increase in CVD and total mortality. Patients with chronic heart failure (CHF) who have TD have a poor prognosis and this is associated with more frequent admissions and increased mortality compared with those who do not have TD. Conversely, in men with symptoms and documented TD, T therapy has been shown to have beneficial effects, namely improvement in exercise capacity in patients with CHF, improvement of myocardial ischaemia and coronary artery disease. Reductions in BMI and waist circumference, and improvements in glycaemic control and lipid profiles, are observed in T-deficient men receiving T therapy. These effects might be expected to translate into benefits and there are more than 100 studies showing CV benefit or improved CV risk factors with T therapy. There are flawed retrospective and prescribing data studies that have suggested increased mortality in treated men, which has led to regulatory warnings, and one placebo-controlled study demonstrating an increase in coronary artery non-calcified and total plaque volumes in men treated with T, which is open for debate. Men with ED and TD who fail to respond to phosphodiesterase type 5 (PDE5) inhibitors can be salvaged by treating the TD. There are data to suggest that T and PDE5 inhibitors may act synergistically to reduce CV risk

Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure

We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01–1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status

N-(2-Amino-3,5-dibromo­benz­yl)-N-methyl­cyclo­hexan-1-aminium p-toluenesulfonate

The title compound, C14H21Br2N2 +·C7H7O3S−, features a salt of protonated bromhexine, a pharmaceutical used in the treatment of respiratory disorders, and the p-toluenesulfonate anion. The crystal packing is stabilized by inter­molecular N—H⋯O, N—H⋯Br and C—H⋯O hydrogen bonds

Testosterone undecanoate is associated with improved ageing male symptoms score in men with type 2 diabetes and adult-onset testosterone deficiency: re-analyzed results from a randomised controlled trial

Aim: To evaluate changes in quality of life via the ageing male symptom scale (AMSS) and somatic, psychological, and sexual sub-scales following testosterone undecanoate (TU) or placebo (P) treatment in men with type 2 diabetes mellitus (T2DM) and adult-onset testosterone deficiency (TD) via a re-analysis of the BLAST (Burntwood, Lichfield, Atherstone, Sutton Coldfield, and Tamworth) randomised controlled trial (RCT). Methods: Analysis of data from the BLAST RCT in men with T2DM and adult-onset TD was performed. Summation baseline and study-end AMSS data were available in 170 men (94: P; 76: TU) with subscale data available in 82 men. Rank-sum and sign-rank tests determined inter/intra-group differences, whilst linear/multiple regression models identified predictors of AMSS change. Results: AMSS improved significantly in P [–2 (median), p = 0.010] and TU [–6 (median), p 49. In the cohort with subscale AMSS data, TU was associated with improvements in somatic, psychological, and sexual subscales, whilst improvement was limited to the somatic subscale in the men on P. TU (reference: P) and higher baseline AMSS were significantly and independently associated with AMSS improvement. The improvement in summation AMSS associated with TU (reference: P) was only evident in men with mild depression and no anxiety (based on baseline Hospital Anxiety and Depression Scale data). Conclusions: TU appeared associated with improved AMSS (summation and subscales) in men with T2DM and adult-onset TD demonstrating symptoms (AMSS ≥ 27) with this benefit mediated by levels of depression and anxiety (European Union Clinical Trials Register, EudraCT 2008-000931-16)

P83 A pilot study to assess peak systolic velocity as a possible marker of atherosclerotic burden using ultrasound

Introduction: Ischemic heart disease (IHD) has been associated with lower peak systolic velocity (PSV) on penile Doppler measurements [1]. This study establishes whether carotid ultrasound (US) PSV was associated with computational fluid dynamics (CFD) outputs, which in turn may contribute to IHD pathogenesis. Methods: A sample of 57 subjects (with IHD: 27, without IHD: 30) had US velocity profiles (left- common carotid artery) determined between 10e12 equispaced points. Bezier curve fitting was used to fit the profile through the measured velocity points for a normalised diameter. PSV was correlated against CFD results such as wall shear stress (WSS) [2]. Difference in PSV between individuals with/without IHD was studied via t-test. Linear regression was carried out to see if peak systolic velocity was associated with CFD outputs. Any significant associations were analysed within stratified groups (with/without IHD). Results: PSV was significantly lower (p Z 0.042) in subjects with IHD (with IHD: 53.6 17.3 cm/s, without IHD: 62.8 16.1 cm/s). PSV was associated with carotid bulb average pressure drop (p < 0.001), area of average bulb WSS (<1 Pa: p Z 0.016, <2 Pa: p Z 0.006, <3 Pa: p Z 0.001). All the above associations remained significant in individuals with IHD (average bulb pressure drop: p Z 0.001, average bulb WSS (<1 Pa: p Z 0.013, <2 Pa: p Z 0.008, <3 Pa: p Z 0.003). In subjects without IHD, PSV was associated with only average bulb pressure drop (p Z 0.016). Conclusions: This study suggests that further work on PSV and its associations with CFD outputs is required in individuals with and without IHD in various vascular beds

Newer Classification System for Fissured Tongue: An Epidemiological Approach

Introduction. Fissured tongue is a commonly encountered tongue disorder in dental practice. But there is a lack of data on different pattern, severity, and association of fissuring with various systemic disorders and other tongue anomalies. This study attempts to establish a classification system for fissured tongue and to know the correlation with the systemic health and other disorders of the tongue. Materials and Methods. A total of 1000 subjects between the age groups of 10 and 80 years were included in the study. Pattern of fissuring, allied systemic diseases, and related tongue anomalies were tabulated. Results. Out of 1000 subjects, 387 subjects presented with fissured tongue. Out of 387 subjects, hypertension was present in 57 cases, 18 subjects had diabetes, and 3 subjects had both hypertension and diabetes. Central longitudinal type was found to be the most common type of tongue fissuring. Conclusion. Fissured tongue has been found to be associated with certain systemic disease and further researches are required to know positive correlation. If a correlation exists, such disorders could be diagnosed earlier by identifying fissured tongue at an earlier age

Adult-onset testosterone deficiency:the usefulness of hormone replacement in reducing mortality in men with this common age-related condition

Adult-onset testosterone deficiency (TD) in men is diagnosed by the finding of low serum testosterone levels and recognised, associated symptoms. The condition has high prevalence in men over 50 years of age, particularly those with type 2 diabetes (T2DM). Accumulating data show adult-onset TD is associated with increased mortality risk. We review the literature and consider the evidence suggesting testosterone therapy (TTh) reduces mortality, especially in men with T2DM. We previously reported that in the Burntwood Lichfield Atherstone Sutton Coldfield Tamworth (BLAST) study screened cohort of men with adult-onset TD and T2DM adult-onset TD was associated with increased mortality with TTh decreasing this higher mortality. The data hinted that the effect was greater in older men. We confirmed this observation with statistical analyses to study the effect of age on the association between adult-onset TD and mortality; Cox regression analysis demonstrated that the reduced risk (hazard ratio: 0.61, 95% CI: 0.38–0.96) following TTh was restricted to men above the median age of 65.89 years. Finally, we speculate on putative mechanisms that may mediate these associations. Heterogeneity in men with adult-onset TD is expected in view of its definition of low testosterone levels together with associated clinical phenotypes that are not always directly related. Many of these classifying phenotypes are associated with increased mortality. Thus, it is perhaps possible that mechanism(s) of all-cause mortality reduction following TTh is via the impact on these associated phenotypes such as the metabolic syndrome (MetS), hyperglycaemia, hypertension, dyslipidaemia, low haematocrit, sex hormone binding levels, erectile dysfunction, etc. We propose that further research studying the effect of TTh takes heterogeneity into account

A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

PURPOSE OF THE STUDY: Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. STUDY DESIGN: We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. RESULTS: In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. CONCLUSIONS: We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics

MGNREGA in Tamil Nadu: a story of success and transformation?

Social protection has emerged as a key driver of development policy at the beginning of the twenty‐first century. It is widely considered a ‘good thing’ that has the potential not only to alleviate poverty and vulnerability, but also to generate more transformative outcomes in terms of empowerment and social justice. Based on an ethnographic study of the implementation of the M ahatma G andhi N ational R ural E mployment G uarantee A ct (MGNREGA ), India's flagship social protection policy, this paper takes a critical look at what this policy's ‘success’ consists of. The study was carried out in T amil Nadu, a state widely presented as a ‘success’ in terms of MGNREGA 's implementation, and describes who participates in the scheme and how success is understood and expressed at different social and bureaucratic levels. In terms of MGNREGA 's outcomes, we conclude that the scheme is benefitting the poorest households – and D alits and women in particular – especially in terms of providing a safety net and as a tool for poverty alleviation. But the scheme does more than that. It has also produced significant transformative outcomes for rural labourers, such as pushing up rural wage levels, enhancing low‐caste workers' bargaining power in the labour market and reducing their dependency on high‐caste employers. These benefits are not only substantial but also transformative in that they affect rural relations of production and contribute to the empowerment of the rural labouring poor. However, in terms of creating durable assets and promoting grassroots democracy, the scheme's outcomes are much less encouraging