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Background: There exist wide variations in healthcare quality within the National Health Service (NHS). A shorter hospital length of stay (LOS) has been implicated as premature discharge, that may in turn lead to adverse consequences. We tested the hypothesis that a short LOS might be associated with increased risk of readmissions within 28 days of hospital discharge and also post-discharge mortality.Methods: We conducted a single-centred study of 32 270 (46.1% men) consecutive alive-discharge episodes (mean age = 64.0 years, standard deviation = 20.5, range = 18-107 years), collected between 01/04/2017 and 31/03/2019. Associations of LOS tertiles (middle tertile as a reference) with readmissions and mortality were assessed using observed/expected ratios, and logistic and Cox regressions to estimate odds (OR) and hazard ratios (HR) (adjusted for age, sex, patients' severity of underlying health status and index admissions), with 95% confidence intervals (CIs).Results: The observed numbers of readmissions within 28 days of hospital discharge or post-discharge mortality were lower than expected (observed: expected ratio < 1) in patients in the bottom tertile (<1.2 days) and middle tertile (1.2-4.3 days) of LOS, whilst higher than expected (observed: expected ratio > 1) in patients in the top tertile (>4.3 days), amongst all ages. Patients in the top tertile of LOS had increased risks for one readmission: OR = 2.32 (95% CI = 1.86-2.88) or ≥2 readmissions: OR = 6.17 (95% CI = 5.11-7.45), death within 30 days: OR = 2.87 (95% CI = 2.34-3.51), and within six months of discharge: OR = 2.52 (95% CI = 2.23-2.85), and death over a two-year period: HR = 2.25 (95% CI = 2.05-2.47). The LOS explained 7.4% and 15.9% of the total variance (r2) in one readmission and ≥2 readmissions, and 9.1% and 10.0% of the total variance in mortality with 30 days and within six months of hospital discharge, respectively. Within the bottom, middle and top tertiles of the initial LOS, the median duration from hospital discharge to death progressively shortened from 136, 126 to 80 days, whilst LOS during readmission lengthened from 0.4, 0.9 to 2.8 days, respectively.Conclusion: Short LOS in hospital was associated with favourable post-discharge outcomes such as early readmission and mortality, and with a delay in time interval from discharge to death and shorter LOS in hospital during readmission. These findings indicate that timely discharge from our hospital meets the aims of the NHS-generated national improvement programme, Getting It Right First Time. [ABSTRACT FROM AUTHOR]

Hypertension is known to be associated with obesity, while its relationship to skeletal muscle, SM (SM; a marker of general health and body function), remains uncertain. We analyzed population-based data of 22 591 men (mean age: 51.6 ± 16.9 years) and 27 845 nonpregnant women (50.6 ± 16.9 years) from Scottish Health Surveys (2003, 2008-2011) and Health Surveys for England (2003-2006, 2008-2013) including 2595 non-insulin- and 536 insulin-treated diabetic patients. Compared with normotensive individuals (no hypertension history with normal systolic [SBP < 140 mm Hg] and diastolic blood pressure [DBP < 90 mm Hg]), percent body fat (BF%) was significantly higher and percent SM lower (P < 0.001) in undetected (no hypertension history with raised SBP ≥ 140 and/or DBP ≥ 90 mm Hg), controlled (hypertension history with normal BP), uncontrolled (hypertension history with raised BP), and untreated hypertension. The prevalences of hypertension within BF% quintiles were 11.8%, 24.8%, 41.4%, 56.8%, and 71.6% and SM% quintiles were 67.5%, 53.3%, 39.5%, 27.4%, and 18.5%. Compared to referent groups (lowest BF% quintile or highest SM% quintile), odds ratio (age, sex, smoking, ethnicity, country, survey year, and diabetes adjusted) for having all types of hypertension in the highest BF% quintile was 5.5 (95% confidence interval = 5.0-5.9) and lowest SM% quintile was 2.3 (2.2-2.5). Compared with those without diabetes, individuals with diabetes had a 2.3-fold-2.6-fold greater risk of hypertension, independent of confounding factors and BF% or SM%. The associations of hypertension with BF% were higher than those with body mass index (BMI). In conclusion, both BF and SM should be considered when analyzing results from health surveys, rather than relying on BMI which does not discriminate between the two. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists. [ABSTRACT FROM AUTHOR]

Objective: Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study.Research Design and Methods: Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1) dyslipidemia (triglyceride >/=2.26 mmol/l or HDL cholesterol 140/90 mmHg or on hypertensive medication); or 3) diabetes (1999 World Health Organization criteria).Results: At baseline, CRP correlated significantly (P < 0.001) with all metabolic indexes in women, but less so in men. After 6 years, 14.2% of men and 16.0% of women developed the metabolic syndrome. Compared with tertile 1, women with CRP in the highest tertile had an increased relative risk of developing the metabolic syndrome by 4.0 (95% CI 2.0-7.9) and diabetes by 5.5 (2.2-13.5); these risks changed minimally after adjusting for BMI or HOMA-IR. The area under receiver-operating characteristic (ROC) curve for the prediction of the development of the syndrome was 0.684 for CRP, increasing to 0.706 when combined with BMI and to 0.710 for a complex model of CRP, BMI, and HOMA-IR.Conclusions: CRP was not a significant predictor of the development of the metabolic syndrome in men. Our data strongly support the notion that inflammation is important in the pathogenesis of diabetes and metabolic disorders in women. [ABSTRACT FROM AUTHOR]

Frequent emergency readmissions may associate with health consequences. We examined the association between readmissions within 28 days of hospital discharge and mortality in 32,270 alive-discharge episodes (18–107 years). Data collected between 1 April 2017 and 31 March 2019 are presented as age- and sex-adjusted hazard ratios (HR) with 95% confidence interval (CI). Compared with no readmission, mortality risk over a 2-year period was increased with one non-identical admission–readmission (AR) episode: HR = 2.4 (2.2–2.7), two or more non-identical AR episodes: HR = 3.0 (2.7–3.4), one identical AR episode: HR = 4.7 (3.6–6.1) and two or more identical AR episodes: HR = 5.0 (3.8–6.7). Eight conditions associated with AR episodes had increased risk of mortality including congestive heart failure: HR = 2.7 (2.2–3.2), chronic pulmonary obstructive disease: HR = 3.0 (2.5–3.6), pneumonia: HR = 2.0 (1.8–2.3), sepsis: HR = 2.2 (1.9–2.5), endocrine disorders: HR = 1.9 (1.6–2.3), urinary tract infection: HR = 1.5 (1.3–1.7), psychiatric disorders: HR = 1.5 (1.1–2.1) and haematological disorders: HR = 1.5 (1.2–1.9). Frequent identical AR episodes, particularly from chronic and agerelated conditions, are associated with increased mortality. [ABSTRACT FROM AUTHOR]

Background: Qatar is located on the north-eastern coast of the Arabian Peninsula. Qatari natives account for less than 15% of the population while the largest migrant group comprising 60% derives from South Asia. Despite projections that stroke burden in Qatar will increase with population ageing, epidemiological studies focusing on stroke in Qatar are relatively scarce. Method: We reviewed the available epidemiological publications relating to Qatar. In addition, we have added to this knowledge by incorporating Qatari data from the on-going Bio-Repository of DNA in Stroke, an independent multinational database of stroke patients. Results: Qatar has low reported incidence and mortality rates of 58 and 9.17 per 100,000 per year, respectively, which may be explained by its middle-aged migrant worker majority population. Correspondingly, South Asian migrants in Qatar suffered younger strokes than Qatari natives (48.7 vs 63.4 years, P<0.001). Among the most common risk factors identified in stroke patients were hypertension (77.9%), diabetes (43.8%) and hypercholesterolemia (28.5%). Ischaemic stroke was the most frequent subtype amongst migrant South Asians (71.1%). The majority of stroke cases had computed tomography and/or magnetic resonance imaging scans, but only 11.1% of ischaemic strokes were thrombolysed. Qataris on one-year follow up were more often found to have died (6.5% vs 0.3%) and had further stroke/transient ischaemic attack events (17.4% vs 6.4%, P¼0.009) compared to South Asians. Conclusion: The burden of stroke is increasing in Qatar, and considerable disparities are observed between the native and migrant populations which likely will require different approaches to management by its healthcare system. [ABSTRACT FROM AUTHOR]

Background: Primary hyperparathyroidism arising from parathyroid adenoma is one of the most common endocrine disorders treated by endocrine surgeons. The adenoma is commonly identified by imaging techniques. The present study evaluated the performance of a portable ultrasound machine (Sonosite MicroMaxx) operated by a surgeon, departmental ultrasound and 99mTc-sestamibi-SPECT/CT by a radiologist in the identification of parathyroid adenomas. Methods: Patient case notes were retrieved from medical records and imaging from picture archiving and communication system over the period from 2006 to 2012. 99mTc-sestamibi-SPECT/CT and departmental ultrasound images were reported by a nuclear radiologist. The ability of each imaging technique in localising parathyroid adenomas was referenced against the actual adenomas identified from parathyroidectomy. Results: With reference to the actual site of the lesion, surgeon-performed ultrasound accurately localised the site of the lesion in 30/33 (90.1%) of cases with a sensitivity of 86.7%, departmental ultrasound accurately localised the site of the lesion in 21/26 (80.1%) of cases with a sensitivity of 79.2%. In 6/75 patients where 99mTc-sestamibi-SPECT/CT did not localise the lesion, departmental ultrasound did not localise any lesions correctly, while surgeon-performed ultrasound successfully located the adenoma in three (50%) of these six patients. Patients whose parathyroid adenomas identified by the surgeon were more likely to have shorter length of stay in hospital: odds ratio = 0.53 (95% confidence interval = 0.30-0.92, p = 0.025). Conclusions: Surgeon-performed ultrasound for immediately pre-operative localisation improves identification of parathyroid adenomas and reduces length of stay in hospital, lending support for the use of this technique by endocrine surgeons. [ABSTRACT FROM AUTHOR]

We evaluated factors and outcomes associated with elapsed time to surgery (ETTS) in 1,081 men and 2,891 women (mean age 83.5 years ±9.1) undergoing hip fracture surgery (from 2009-2019). Mortality rates were 4.8%, 6.3%, 6.2% and 10.3% (chi-squared 19.0; p<0.001), and hospital length of stay (LOS) >19 days were 31.9%, 32.8%, 33.8% and 43.2% (chi-squared 18.5; p<0.001) for ETTS <24 hours, 24-35 hours, 36-47 hours and ≥48 hours, respectively. There were no differences between ETTS categories for failure to mobilise within 1 day of surgery, pressure ulcers or discharge to nursing care. After adjustment for age, sex, American Society of Anesthesiologists' score and years of data collection, compared with Sunday, the risk of ETTS ≥36 hours was highest on Friday (odds ratio (OR) 3.50; 95% confidence interval (CI) 2.43-5.03) and Saturday (OR 4.70; 95% CI 3.26-6.76). Compared with ETTS <24 hours, there were increases in the risk of death when ETTS ≥48 hours (OR 2.31; 95% CI 1.47-3.65) and LOS >19 days (OR 1.34; 95% CI 1.02-1.75). The median (interquartile range (IQR)) LOS for ETTS <24 hours was 12.7 days (IQR 8.0-23.0), 24-35 hours was 13.5 days (IQR 8.4-22.9), 36-47 hours was 14.1 days (IQR 8.9-23.3) and ≥48 hours was 16.9 (IQR 10.8-27.0; p<0.001). The 10-year period of collection did not change the conclusion. Admissions towards the end of the week are associated with delayed ETTS for hip fractures, while delay in surgery, particularly beyond 48 hours, is associated with increased risk of mortality and prolonged LOS. [ABSTRACT FROM AUTHOR]

Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment. Methods: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Results: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range = 36–62) and body mass index of 37.4 kg/m2 (range = 27–56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval =59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports. Conclusions: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels. [ABSTRACT FROM AUTHOR]

Background: Smoking and dyslipidaemia are known individual risk factors of coronary artery disease (CAD). The present study examined the combined risk of smoking and dyslipidaemia on coronary atherosclerosis. Methods: Coronary artery calcium (CAC), measured by cardiac CT, was used to assess the extent of CAD, which was related to smoking and dyslipidaemia using logistic regression, adjusted for age, sex, hypertension, BMI and family history of ischaemic heart disease. Results: Seventy-one patients (46 men, 25 women: median age of 53.7yrs; IQR = 47.0–59.5) were recruited. The mean log10 CAC score in never-smokers without dyslipidaemia (reference group) was 0.37 (SD = 0.73), while the value in those with a history of smoking was 0.44 ± 0.48 (mean difference: 0.07, 95%CI:–0.67 to 0.81, p = 0.844), dyslipidaemia was 1.07 ± 1.08 (mean difference: 0.71, 95%CI: 0.24 to 1.17, p = 0.003), and both risk factors was 1.82 ± 0.64 (mean difference: 1.45, 95%CI:0.88 to 2.02, p < 0.001). For individuals in the reference group, the proportions with none, one and multiple vessel disease were 80.6%, 16.1% and 3.2%; for those with a history of smoking or with dyslipidaemia were 50.0%, 25.0% and 25.0%; and for those with both risk factors were 8.3%, 25.0% and 66.7%. Patients with a history of both risk factors had greater adjusted risks of having one- vessel disease - OR = 14.3 (95%CI = 2.1–98.2) or multiple vessel disease: OR = 51.8 (95%CI = 4.2–609.6). Conclusions: Smoking and dyslipidaemia together are associated with high coronary artery calcification and CAD, independent of other major risk factors. [ABSTRACT FROM AUTHOR]

Stress from obstructive sleep apnea (OSA) stimulates catecholamine release consequently exacerbating hypertension. However, different studies have shown a conflicting impact of continuous positive airway pressure (CPAP) treatment in patients with OSA on catecholamine levels and blood pressure. We aimed to examine changes to catecholamine levels and blood pressure in response to CPAP treatment. We conducted a meta‐analysis of data published up to May 2020. The quality of the studies was evaluated using standard tools for assessing the risk of bias. Meta‐analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference (MD) for systolic (SBP) and diastolic blood pressure (DBP). A total of 38 studies met our search criteria; they consisted of 14 randomized control trials (RCT) totaling 576 participants and 24 prospective cohort studies (PCS) of 547 participants. Mean age ranged between 41 and 62 year and body mass index between 27.2 and 35.1 kg/m2. CPAP treatment reduced 24‐hour urinary noradrenaline levels both in RCT (SMD = −1.1; 95% confidence interval (CI): −1.63 to − 0.56) and in PCS (SMD = 0.38 (CI: 0.24 to 0.53). SBP was also reduced by CPAP treatment in RCT (4.8 mmHg; CI: 2.0‐7.7) and in PCS (7.5 mmHg; CI: 3.3‐11.7). DBP was similarly reduced (3.0 mmHg; CI: 1.4‐4.6) and in PCS (5.1 mmHg; CI: 2.3‐8.0). In conclusion, CPAP treatment in patients with OSA reduces catecholamine levels and blood pressure. This suggests that sympathetic activity plays an intermediary role in hypertension associated with OSA‐related stress. [ABSTRACT FROM AUTHOR]

Background the 4AT (Alertness, Abbreviated Mental Test-4, Attention and Acute change or fluctuating course), a tool to screen cognitive impairment and delirium, has recently been recommended by the Scottish Intercollegiate Guidelines Network. We examined its ability to predict health outcomes among patients admitted with hip fractures to a single hospital between January 2018 and June 2019. Methods the 4AT was performed within 1 day after hip surgery. A 4AT score of 0 means unlikely delirium or severe cognitive impairment (reference group); a score of 1–3 suggests possible chronic cognitive impairment, without excluding possibility of delirium; a score ≥ 4 suggests delirium with or without chronic cognitive impairment. Logistic regression, adjusted for: age; sex; nutritional status; co-morbidities; polypharmacy; and anticholinergic burden, used the 4AT to predict mobility, length of stay (LOS), mortality and discharge destination, compared with the reference group. Results from 537 (392 women, 145 men: mean = 83.7 ± standard deviation [SD] = 8.8 years) consecutive patients, 522 completed the 4AT; 132 (25%) had prolonged LOS (>2 weeks) and 36 (6.8%) died in hospital. Risk of failure to mobilise within 1 day of surgery was increased with a 4AT score ≥ 4 (OR = 2.4, 95% confidence interval [CI] = 1.3–4.3). Prolonged LOS was increased with 4AT scores of 1–3 (OR = 2.4, 95%CI = 1.4–4.1) or ≥4 (OR = 3.1, 95%CI = 1.9–6.7). In-patient mortality was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.2–8.2) but not with a 4AT score of 1–3. Change of residence on discharge was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.4–6.8). These associations persisted after excluding patients with dementia. 4AT score = 1–3 and ≥ 4 associated with increased LOS by 3 and 6 days, respectively. Conclusions for older adults with hip fracture, the 4AT independently predicts immobility, prolonged LOS, death in hospital and change in residence on discharge. [ABSTRACT FROM AUTHOR]

Background: Prevention of thromboembolism by novel oral anticoagulants is increasing, whilst use of vitamin K antagonists is on the decline. We assessed changes in the use of these anticoagulants in treating non-valvular atrial fibrillation between 2014 and 2018. Methods: One-hundred and sixty-two consecutive patients (95 men, 67 women) with non-valvular atrial fibrillation, mean age 72.3 years (standard deviation = 11.0), underwent cardiac assessment in a single cardiac unit. Use of anticoagulants at the time of investigation was documented: overall 83 (51.2%) patients were prescribed novel oral anticoagulants and 79 (48.8%) warfarin treatment. Trends in treatment rates with either anticoagulant class over time were characterised by calculating the average annual percentage change using a Joinpoint Regression Program 4.7.0.0. Results: There were diverging trends in anticoagulant treatment from 2014 to 2018 without join points: yearly increase in novel oral anticoagulant treatment (41.9, 45.5, 53.7, 53.1 and 72.7%, average annual percentage change = 16.2%, 95% confidence interval = 5.8% to 27.5%, p < 0.001), and decrease in warfarin treatment (57.1, 54.5, 46.3, 46.9 and 27.3%, average annual percentage change = −14.4%, 95% confidence interval = −25.2% to −2.1%, p < 0.001). Conclusions: Changing trends in treatment with anticoagulants for patients with non-valvular atrial fibrillation observed within less than two years provide important information to healthcare services to estimate future pharmaco-economic costs for such treatments. [ABSTRACT FROM AUTHOR]

Background: Left ventricular ejection fraction (LVEF) is generally measured by echocardiography but is increasingly available with myocardial perfusion scintigraphy. With myocardial perfusion scintigraphy, the threshold of LVEF below which there is a risk for myocardial infarct or sudden cardiac death is higher for women (51%) than for men (43%). We tested the hypothesis that such a sex difference may also occur with echocardiography and myocardial perfusion scintigraphy. Methods: Four hundred and four men, mean age = 67.7 ± SD = 12.3 yr; 339 women, 67.7 ± 11.7 yr had separate myocardial perfusion scintigraphy and echocardiography examinations within six months. A subset of 327 of these patients (181 men, 68.8 ± 12.1 yr; 146 women, 66.4 ± 12.1 yr) had examinations within one month and were additionally analysed as this sub-group. Myocardial perfusion scintigraphy and echocardiography were used to measure LVEF at rest and their agreement (neither considered as a reference method) was assessed by Bland–Altman plots: LVEF difference (myocardial perfusion scintigraphy minus echocardiography) against average LVEF ( MPS + Echo 2 ). Results: Of patients who had myocardial perfusion scintigraphy and echocardiography performed within six months, mean LVEF difference = +1.1% (95% limits of agreement: −19.3 to +21.6) in men but +10.9% (−10.7 to +32.5) in women. LVEF difference diverged from zero marginally in men (mean difference = +1.1, 95%CI = +0.1 to +2.1, p = 0.028) but more in women (+10.9, +9.8 to +12.1, p < 0.001). The LVEF difference correlated with average LVEF itself in both men (r = 0.305, p < 0.001) and women (r = 0.361, p < 0.001), and with age in women (r = 0.117, p = 0.031). Similar results were observed for the subset. Conclusions: Caution should be taken when interpreting LVEF measured by different techniques due to their wide limits of agreement and systematic bias, more markedly in women. [ABSTRACT FROM AUTHOR]

Background: Smoking and dyslipidaemia are known individual risk factors of coronary artery disease (CAD). The present study examined the combined risk of smoking and dyslipidaemia on coronary atherosclerosis. Methods: Coronary artery calcium (CAC), measured by cardiac CT, was used to assess the extent of CAD, which was related to smoking and dyslipidaemia using logistic regression, adjusted for age, sex, hypertension, BMI and family history of ischaemic heart disease. Results: Seventy-one patients (46 men, 25 women: median age of 53.7yrs; IQR = 47.0–59.5) were recruited. The mean log10 CAC score in never-smokers without dyslipidaemia (reference group) was 0.37 (SD = 0.73), while the value in those with a history of smoking was 0.44 ± 0.48 (mean difference: 0.07, 95%CI:–0.67 to 0.81, p = 0.844), dyslipidaemia was 1.07 ± 1.08 (mean difference: 0.71, 95%CI: 0.24 to 1.17, p = 0.003), and both risk factors was 1.82 ± 0.64 (mean difference: 1.45, 95%CI:0.88 to 2.02, p < 0.001). For individuals in the reference group, the proportions with none, one and multiple vessel disease were 80.6%, 16.1% and 3.2%; for those with a history of smoking or with dyslipidaemia were 50.0%, 25.0% and 25.0%; and for those with both risk factors were 8.3%, 25.0% and 66.7%. Patients with a history of both risk factors had greater adjusted risks of having one- vessel disease - OR = 14.3 (95%CI = 2.1–98.2) or multiple vessel disease: OR = 51.8 (95%CI = 4.2–609.6). Conclusions: Smoking and dyslipidaemia together are associated with high coronary artery calcification and CAD, independent of other major risk factors. [ABSTRACT FROM AUTHOR]

Background: Left ventricular ejection fraction (LVEF) is generally measured by echocardiography but is increasingly available with myocardial perfusion scintigraphy. With myocardial perfusion scintigraphy, the threshold of LVEF below which there is a risk for myocardial infarct or sudden cardiac death is higher for women (51%) than for men (43%). We tested the hypothesis that such a sex difference may also occur with echocardiography and myocardial perfusion scintigraphy. Methods: Four hundred and four men, mean age = 67.7 ± SD = 12.3 yr; 339 women, 67.7 ± 11.7 yr had separate myocardial perfusion scintigraphy and echocardiography examinations within six months. A subset of 327 of these patients (181 men, 68.8 ± 12.1 yr; 146 women, 66.4 ± 12.1 yr) had examinations within one month and were additionally analysed as this sub-group. Myocardial perfusion scintigraphy and echocardiography were used to measure LVEF at rest and their agreement (neither considered as a reference method) was assessed by Bland–Altman plots: LVEF difference (myocardial perfusion scintigraphy minus echocardiography) against average LVEF ( MPS + Echo 2 ). Results: Of patients who had myocardial perfusion scintigraphy and echocardiography performed within six months, mean LVEF difference = +1.1% (95% limits of agreement: −19.3 to +21.6) in men but +10.9% (−10.7 to +32.5) in women. LVEF difference diverged from zero marginally in men (mean difference = +1.1, 95%CI = +0.1 to +2.1, p = 0.028) but more in women (+10.9, +9.8 to +12.1, p < 0.001). The LVEF difference correlated with average LVEF itself in both men (r = 0.305, p < 0.001) and women (r = 0.361, p < 0.001), and with age in women (r = 0.117, p = 0.031). Similar results were observed for the subset. Conclusions: Caution should be taken when interpreting LVEF measured by different techniques due to their wide limits of agreement and systematic bias, more markedly in women. [ABSTRACT FROM AUTHOR]

Background: Prevention of thromboembolism by novel oral anticoagulants is increasing, whilst use of vitamin K antagonists is on the decline. We assessed changes in the use of these anticoagulants in treating non-valvular atrial fibrillation between 2014 and 2018. Methods: One-hundred and sixty-two consecutive patients (95 men, 67 women) with non-valvular atrial fibrillation, mean age 72.3 years (standard deviation = 11.0), underwent cardiac assessment in a single cardiac unit. Use of anticoagulants at the time of investigation was documented: overall 83 (51.2%) patients were prescribed novel oral anticoagulants and 79 (48.8%) warfarin treatment. Trends in treatment rates with either anticoagulant class over time were characterised by calculating the average annual percentage change using a Joinpoint Regression Program 4.7.0.0. Results: There were diverging trends in anticoagulant treatment from 2014 to 2018 without join points: yearly increase in novel oral anticoagulant treatment (41.9, 45.5, 53.7, 53.1 and 72.7%, average annual percentage change = 16.2%, 95% confidence interval = 5.8% to 27.5%, p < 0.001), and decrease in warfarin treatment (57.1, 54.5, 46.3, 46.9 and 27.3%, average annual percentage change = −14.4%, 95% confidence interval = −25.2% to −2.1%, p < 0.001). Conclusions: Changing trends in treatment with anticoagulants for patients with non-valvular atrial fibrillation observed within less than two years provide important information to healthcare services to estimate future pharmaco-economic costs for such treatments. [ABSTRACT FROM AUTHOR]

Background: Cowden's syndrome (OMIM:158350), a rare genetic disorder (incidence ~ 1:250,000), is caused by mutations of the tumor suppressor gene PTEN. In this report, we describe clinical manifestations of a 56-year-old patient diagnosed with Cowden's syndrome and his family with PTEN mutations. The family has an unusually high number of offspring with autism spectrum disorder.Case Presentation: Except for his 80-year-old Caucasian father, all of our index case's living Caucasian kindred (three children, brother, and nephew) had PTEN mutations and macrocephaly. Prior to genetic testing, his mother and sister died of breast cancer at 42 and 38 years old, respectively. After PTEN mutation was identified, our patient underwent complete thyroidectomy (histology showing micropapillary carcinoma) and right nephrectomy for renal cell carcinoma. All of his three children (13-year-old son, 11- and 8-year-old daughters) have been diagnosed with autism spectrum disorder. His son and brother underwent total thyroidectomy. His nephew had thyroid nodules. Management of Cowden's syndrome requires clinical examinations and investigations every 6 to 12 months from 18 years old or 5 years before the family's earliest age of cancer diagnosis and should focus on all clinical manifestations associated with PTEN mutations to identify early abnormal changes in skin, breasts, thyroid, endometrium, gut, and kidneys. Input from specialists across different disciplines is necessary.Conclusions: We describe a man and his family with PTEN mutations who have increased risk of cancers and an unusually high number of offspring with autism spectrum disorder. Early recognition and close surveillance are vital in order to provide treatment and early screening for asymptomatic at-risk relatives. [ABSTRACT FROM AUTHOR]

There exist published literature for cardiovascular disease (CVD) risk monitoring in cancer survivors but the extent of monitoring in clinical oncology practice is unknown. We performed an interactive survey at a Royal College of Physicians conference (11 November 2016) attended by practitioners with an interest in late effects of cancer treatment and supplemented the survey with an audit among 32 lung cancer survivors treated at St Peter's NHS Hospital in 2012-2016. Among the practitioners, 40% reported CVD risk monitoring performed at least annually, which is compatible with European Group for Blood and Marrow Transplantation Guidelines, but 31% indicated that monitoring was never performed. In contrast, 77% felt that at least an annual assessment was required (p<0.001). Corroborating these data, among the lung cancer survivors, 31% and 16% had lipids or glucose/HbA1C measured annually, and 28% and 31% had never had these tests performed since their cancer treatment. Alerting healthcare providers to review protocols may help reduce CVD after cancer treatments. [ABSTRACT FROM AUTHOR]

Context: The androgen receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive. Objective: To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints that are influenced by testosterone (T) levels in middle-aged and elderly European men. Design: Multinational European observational prospective cohort study. Participants: A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis. Main outcome measures: Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated as both a continuous and a categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels. Results: The AR CAG repeat, when used as a continuous or a categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels.Conclusion: Within a 4-year time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels. [ABSTRACT FROM AUTHOR]

Background: Dementia is a major public health challenge and China has the largest population with dementia in the world. However, dementia care and caregivers for Chinese are less investigated. Objectives and design: To evaluate demographic and socio-economic influences on dementia care, management patterns and caregiver burden in a household community-dwelling-based survey, using participants’ care receipts and Zarit scale. Setting and participants: Rural and urban communities across six provinces of China comprising 4837 residents aged ≥60 years, in whom 398 had dementia and 1312 non-dementia diseases. Results: People with dementia were less likely to receive care if they were living in rural compared to urban areas (Odd ratio (OR) = 0.20; 95%CI: 0.10–0.41), having education level below compared to above secondary school (OR = 0.24; 95%CI: 0.08–0.70), manual labourer compared to non-manual workers (OR = 0.27; 95%CI: 0.13–0.55), having personal annual income below RMB 10,000 yuan (£1000) compared to above (OR = 0.37; 95%CI: 0.13–0.74) or having four or more than compared to less four children (OR = 0.52; 95%CI: 0.27–1.00). Caregivers for dementia compared with those for non-dementia diseases were younger and more likely to be patients’ children or children in-law, had lower education and spent more caring time. Caregiver burden increased with low education, cutback on work and caring for patients who were younger or living in rural areas, and this caregiver burden was three-fold greater than that for non-dementia diseases. Conclusions: There are a number of inequalities in dementia care and caregiver burden in China. Reducing the socio-economic gap and increasing education may improve community care for people with dementia and preserve caregivers’ well-being. [ABSTRACT FROM AUTHOR]

Background: low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men. Methods: men aged 40-79 years were recruited for participation in a prospective study of male ageing: the European Male Ageing Study (EMAS). At baseline, subjects attended for quantitative ultrasound (QUS) of the heel (Hologic—SAHARA) and completed questionnaires on lifestyle factors and co-morbidities. Height and weight were measured. After a median of 4.3 years, subjects were invited to attend a follow-up assessment, and reasons for non-participation, including death, were recorded. The relationship between QUS parameters (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) and mortality was assessed using Cox proportional hazards model. Results: from a total of 3,244 men (mean age 59.8, standard deviation [SD] 10.8 years), 185 (5.7%) died during the follow-up period. After adjusting for age, centre, body mass index, physical activity, current smoking, number of co-morbidities and general health, each SD decrease in BUAwas associated with a 20% higher risk of mortality (hazard ratio [HR] per SD = 1.2; 95% confidence interval [CI] = 1.0-1.4). Compared with those in higher quintiles (2nd-5th), those in the lowest quintile of BUA and SOS had a greater mortality risk (BUA: HR = 1.6; 95% CI = 1.1-2.3 and SOS: HR = 1.6; 95% CI = 1.2-2.2). Conclusion: lower heel ultrasound parameters are associated with increased mortality in European men. [ABSTRACT FROM AUTHOR]

Presents the authors' response to comments on their article on the relation of C-reactive protein (CRP) with type 2 diabetes. Importance of inflammation to the pathogenesis of type 2 diabetes in women; Reason for the inability to find an association between CRP and diabetes risk in men.

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40–79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here. [ABSTRACT FROM AUTHOR]

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40–79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here. [ABSTRACT FROM AUTHOR]

Background: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH.Setting: cross-sectional analysis within the European Male Ageing Study (EMAS).Participants: a total of 1,504 community-dwelling men aged 60–79 years.Methods: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models.Results: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26–1.67) and frail (ROR = 1.89; 95% CI: 1.30–2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01–1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH.Conclusion: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further. [ABSTRACT FROM PUBLISHER]

The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance. [ABSTRACT FROM AUTHOR]

Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. Design and methods: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E2) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. Results: In univariate analyses, free T levels were lower (P=0.02) and E2 and LH levels were higher (P<0.05) in men with vitamin D deficiency <25(OH)D !50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E2 and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. Design: A cross-sectional population-based survey. Methods: Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (b C-terminal cross-linked telopeptide (b-cTX)), total testosterone, total oestradiol (E2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dualenergy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres Results: A total of 3120, mean age 59.9 years (S.D.Z11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E2 were negatively associated with &bgr;-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both &bgr;-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. Conclusions: E2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r²≥0.8) within MAP3K14 (±10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health. [ABSTRACT FROM AUTHOR]

Purpose Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40–79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. [ABSTRACT FROM AUTHOR]

Background: A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested. Methods: Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication. Results: Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (b(SD) = 0.07, p = 0.032) but not BUA (b(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (b(SD) = -0.22, p = 0.014), FN (b(SD) = -0.31,p = 0.001) and TH (b(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL. Conclusions: We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men. [ABSTRACT FROM AUTHOR]