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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]

The LACE index scoring tool has been designed to predict hospital readmissions in adults. We aimed to evaluate the ability of the LACE index to identify children at risk of frequent readmissions. We analysed data from alive-discharge episodes (1 April 2017 to 31 March 2019) for 6546 males and 5875 females from birth to 18 years. The LACE index predicted frequent all-cause readmissions within 28 days of hospital discharge with high accuracy: the area under the curve = 86.9% (95% confidence interval = 84.3–89.5%, p < 0.001). Two-graph receiver operating characteristic curve analysis revealed the LACE index cutoff to be 4.3, where sensitivity equals specificity, to predict frequent readmissions. Compared with those with a LACE index score = 0–4 (event rates, 0.3%), those with a score > 4 (event rates, 3.7%) were at increased risk of frequent readmissions: age- and sex-adjusted odds ratio = 12.4 (95% confidence interval = 8.0–19.2, p < 0.001) and death within 30 days of discharge: OR = 5.0 (95% CI = 1.5–16.7). The ORs for frequent readmissions were between 6 and 14 for children of different age categories (neonate, infant, young child and adolescent), except for patients in the child category (6–12 years) where odds ratio was 2.8. Conclusion: The LACE index can be used in healthcare services to identify children at risk of frequent readmissions. Focus should be directed at individuals with a LACE index score above 4 to help reduce risk of readmissions. What is Known: • The LACE index scoring tool has been widely used to predict hospital readmissions in adults. What is New: • Compared with children with a LACE index score of 0–4 (event rates, 0.3%), those with a score > 4 are at increased risk of frequent readmissions by 14-fold. • The cutoff of a LACE index of 4 may be a useful level to identify children at increased risk of frequent readmissions. [ABSTRACT FROM AUTHOR]

Purpose: With improving nutrition and health, athletes have grown taller and heavier over the past century. Since there is no weight restriction in the heavyweight class, secular changes in anthropometric measurements of heavyweight boxers may mirror those of contemporary general populations. Objectives: We aimed to (1) examine secular trends in adiposity and musculoskeletal measurements in heavyweight boxers, (2) determine anthropometric differences between champions and unsuccessful challengers. Methods: Detailed demographics taken at time of contest (first official World Championship to current contest: 1889–2019) were collected from media archives. Results: All 237 boxers (83 champions, 154 challengers) contesting a recognised heavyweight World Championships were identified. They had mean (± SD) age = 28.9 ± 4.1 years, height = 187.3 ± 6.5 cm, reach = 195.2 ± 9.4 cm, weight = 97.5 ± 11.5 kg, BMI = 27.8 ± 2.4 kg/m2 and waist = 87.9 ± 6.2 cm. Contest years explained 25.9% (p < 0.001) of the variance in BMI for champions and 30.9% (p < 0.001) for challengers, 9.1% (p < 0.071) in WC for champions and 19.9% (p < 0.001) for challengers. Contest years correlated with height (r = 0.531, p < 0.001), reach (r = 0.341, p < 0.001), weight (r = 0.603, p < 0.001) and BMI (r = 0.370, p = 0.001) among all documented boxers, and with waist only in challengers (r = 0.349, p < 0.001) but not in champions (r = 0.078, p = 0.509). Compared with challengers, champions had greater stature by + 3.4 cm (p < 0.001), reach + 3.6 cm (p = 0.005) and weight + 3.7 kg (p = 0.017), with similar BMI and waist. Champions had larger biceps and forearms but did not differ from challengers in other musculoskeletal dimensions. Conclusions: Over 130 years elite heavyweight boxers have increased in size (BMI) and reach but waists in champions have remained static. Being heavier, taller with longer and bigger arms, but with similar in BMI and waist, appear to be differentiating factors between champions and challengers. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is managed primarily by dopamine agonists and physiotherapy while virtual reality (VR) has emerged recently as a complementary method. The present study reviewed the effectiveness of VR in rehabilitation of patients with PD.Methods: Literature search up to June 2019 identified ten studies (n = 343 participants) suitable for meta-analysis and 27 studies (n = 688 participants) for systematic review. Standard mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random effects model.Results: In meta-analysis, compared with active rehabilitation intervention, VR training led to greater improvement of stride length, SMD = 0.70 (95%CI = 0.32-1.08, p = 0.0003), and was as effective for gait speed, balance and co-ordination, cognitive function and mental health, quality of life and activities of daily living. Compared with passive rehabilitation intervention, VR had greater effects on balance: SMD = 1.02 (95%CI = 0.38-1.65, p = 0.002). Results from single randomised controlled trials showed that VR training was better than passive rehabilitation intervention for improving gait speed SMD = 1.43 (95%CI = 0.51-2.34, p = 0.002), stride length SMD = 1.27 (95%CI = 0.38-2.16, p = 0.005) and activities of daily living SMD = 0.96 (95%CI = 0.02-1.89). Systematic review showed that VR training significantly (p < 0.05) improved motor function, balance and co-ordination, cognitive function and mental health, and quality of life and activities of daily living.Conclusion: VR used in rehabilitation for patients with PD improves a number of outcomes and may be considered for routine use in rehabilitation. [ABSTRACT FROM AUTHOR]

Background: The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants.Methods: PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale).Results: Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS.Conclusions: We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene. [ABSTRACT FROM AUTHOR]

Background: Urgent reversal of vitamin K antagonists (VKAs) is required for major bleeding or urgent surgery by intravenous vitamin K with either prothrombin complex concentrates (PCCs) or fresh frozen plasma (FFP). However, there is lack of consensus regarding the superiority of either reversal agent. We sought to compare the performance of PCC and FFP in urgent reversal of VKA. Methods: A meta-analysis was conducted up to November 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Seventeen studies comprising 2606 participants met the inclusion criteria. Compared with FFP treatment, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.60, 95% CI 0.40–0.90, p = 0.01), better reversal of INR (OR 7.36, 95% CI 4.18–12.98; p < 0.00001) and lower risk of at least one treatment-related adverse event (OR 0.45, 95% CI 0.26–0.80, p = 0.006). Among patients with VKA-associated intracranial haemorrhage, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.58, 95% CI 0.35–0.94, p = 0.03) and better reversal of INR (OR 6.52, 95% CI 1.66–25.59, p = 0.007). There were no differences between these two agents in thrombogenicity, requirement for and quantity of red blood cell transfusions, all adverse events, fluid overload or disability on discharge or at 90 days. Conclusions: As an agent for urgent reversal of VKA, PCC outperforms FFP in 90-day all-cause mortality including those with VKA-related intracranial haemorrhage, INR reversal and treatment-related adverse events. [ABSTRACT FROM AUTHOR]

Objectives: The National Institute of Health and Clinical Excellence and The Royal College of Physicians recommend transferring thrombolysed patients with stroke to a hyperacute stroke unit (HASU) within 4 h from hospital arrival (TArrival-HASU), but there is paucity of evidence to support this cut-off. We assessed if a shorter interval within this target threshold conferred a significant improvement in patient mortality.Design: We conducted a retrospective analysis of prospectively collected data from the Sentinel Stroke National Audit Programme.Setting: Four major UK hyperacute stroke centres between 2014 and 2016.Participants: A total of 183 men (median age = 75 years, IQR = 66-83) and 169 women (median age = 81 years, IQR = 72.5-88) admitted with acute ischaemic stroke.Main Outcome Measures: We evaluated TArrival-HASU in relation to inpatient mortality, adjusted for age, sex, co-morbidities, stroke severity, time between procedures, time and day on arrival.Results: There were 51 (14.5%) inpatient deaths. On ROC analysis, the AUC (area under the curve) was 61.1% (52.9-69.4%, p = 0.01) and the cut-off of TArrival-HASU where sensitivity equalled specificity was 2 h/15 min (intermediate range = 30 min to 3 h/15 min) for predicting mortality. On logistic regression, compared with the fastest TArrival-HASU group within 2 h/15 min, the slowest TArrival-HASU group beyond upper limit of intermediate range (≥ 3 h/15 min) had an increased risk of mortality: 5.6% vs. 19.6%, adjusted OR = 5.6 (95%CI:1.5-20.6, p = 0.010).Conclusions: We propose three new alarm time zones (A1, A2 and A3) to improve stroke survival: "A1 Zone" (TArrival-HASU < 2 h/15 min) indicates that a desirable target, "A2 Zone" (TArrival-HASU = 2 h/15 min to 3 h/15 min), indicates increasing risk and should not delay any further, and "A3 Zone" (TArrival-HASU ≥ 3 h/15 min) indicates high risk and should be avoided. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. Methods: The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. Results: The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6–33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1–50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1–37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53–4.25, p < 0.001), 3.61 (95% CI: 2.90–4.51, p < 0.001), and 5.24 (95% CI: 3.93–7.00, p < 0.001), respectively. Conclusion: South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations. [ABSTRACT FROM AUTHOR]

Purpose: While weight gain and obesity are the dominant factors, dietary sugar and specifically sugar-sweetened beverages (SSB) has been implicated in causing type 2 diabetes (T2DM). We assessed how much of the apparent effect of SSB is explained by adiposity, but not captured by adjustment for BMI, which is a poor index of body fat. Methods: We examined data from 5187 adults (mean age 50.8 years, SD = 16.4, 172 (3.3%) T2DM), from the Scottish Health Survey 2003 and 2008–2010 databases. Logistic regression was used to assess the association between SSB consumption and T2DM (non-insulin treated) and its attenuation (reduction in odds ratios, ORs), after entering published anthropometric indices of adiposity into the regression model, adjusted for age, sex, social class, education, smoking, alcohol consumption and physical activity. Results: Compared with low SSB categories ("less often/never", once/week or 1–3 times/month), the OR without adiposity adjustment for having T2DM in high SSB consumers (2–3, 4–5, ≥ 6/day) was 2.56 (95% CI 1.12–5.83; p = 0.026). That OR was marginally changed by adjusting for BMI (+ 4.3%), WC (+ 5.5%) or total body fat (− 4.3%), but greatly attenuated by adjusting for estimated %body fat (− 23.4%). These indices had similar influences on the associations between SSB and T2DM combining known T2DM patients with unknown HbA1c > 6.5%, > 48 mmol/mol. Conclusions: Associations between SSB and T2DM are attenuated more markedly by adjustment with estimated %body fat than with BMI, indicating an adiposity effect not captured using BMI. Future research should employ best available estimates of adiposity. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the Hypoglycaemia Symptom Rating Questionnaire (HypoSRQ©) and relationships between self-reported hypoglycaemia and hypoglycaemia measured using blinded continuous glucose monitoring (CGM).Methods: Diabetes outpatients (n = 113) recruited from Ashford and St. Peter's Hospital completed the HypoSRQ (recent weeks version) and provided clinical information. Thirty participants used blinded CGM for six days and completed the HypoSRQ (24-hour version) for seven days, at the end of each week (7-day version), and after four weeks (recent weeks version).Results: The HypoSRQ had a single-factor structure and excellent internal consistency (α = 0.90). There was high correspondence in recalled symptoms, bother ratings and hypoglycaemic episodes across one week and four weeks (r = 0.84-0.98, p < 0.001). HypoSRQ-reported hypoglycaemia correlated significantly with CGM-measured hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) frequency (r = 0.72, p < 0.001) across six days. The magnitude of the correlation increased when the person's own threshold for detecting hypoglycaemia was used (r = 0.78, p < 0.001). The number of days (out of six) a person reported symptoms of hypoglycaemia was associated with the number of days CGM detected hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) (r = 0.83, p < 0.001) and remained significant after controlling for covariates.Conclusions: Psychometric properties of the HypoSRQ make it attractive for use in people with insulin-treated diabetes. The HypoSRQ may be a less-invasive and more-economical alternative to CGM. [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]

Objective Hyperandrogenism in congenital adrenal hyperplasia ( CAH) provides an in vivo model for exploring the effect of androgens on erythropoiesis in women. We investigated the association of androgens with haemoglobin (Hb) and haematocrit (Hct) in women with CAH. Design Cross-validation study. Patients Women with CAH from Sheffield Teaching Hospitals, UK (cohort 1, the training set: n = 23) and National Institutes of Health, USA (cohort 2, the validation set: n = 53). Measurements Androgens, full blood count and basic biochemistry, all measured on the same day. Demographic and anthropometric data. Results Significant age-adjusted correlations ( P < 0·001) were observed for Ln testosterone with Hb and Hct in cohorts 1 and 2 (Hb r = 0·712 & 0·524 and Hct r = 0·705 & 0·466), which remained significant after adjustments for CAH status, glucocorticoid treatment dose and serum creatinine. In the combined cohorts, Hb correlated with androstenedione ( P = 0·002) and 17-hydroxyprogesterone ( P = 0·008). Hb and Hct were significantly higher in cohort 1 than those in cohort 2, while there were no group differences in androgen levels, glucocorticoid treatment dose or body mass index. In both cohorts, women with Hb and Hct in the highest tertile had significantly higher testosterone levels than women with Hb and Hct in the lowest tertile. Conclusions In women with CAH, erythropoiesis may be driven by androgens and could be considered a biomarker for disease control. [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]

The originally published version of this article contained typesetting errors in Figure 4. [ABSTRACT FROM AUTHOR]

Aims To assess factors associated with excess rates of fractures in women with Turner's syndrome (TS). Outcome measures History of bone fracture and treatment with oestrogen, growth hormone (GH), oxandrolone and thyroxine, anthropometry, blood measurements of calcium, vitamin D (25-hydroxycholecalciferol), parathyroid hormone and karyotype, pure tone audiometry and spinal bone mineral density (BMD). Results One hundred and seventy-seven consecutive women with TS, aged 19–60 years, were interviewed with respect to bone fracture history. BMD and hearing information were recorded from the medical notes. Karyotype was available in 94% of patients (55% monosomy 45X, 45% other X chromosome defects and mosaicism). Subjects had a mean (SD) height of 1·47 (0·07) m and BMI 25·8 (5·2) kg/m2. The prevalence of fractures was 32% and hearing impairment 84% (18% conductive and 67% sensorineual, of whom 32% and 16%, respectively, used hearing aids). BMD T score was < −1 in 55% of women and < −2·5 in 9%. Fracture rates were higher in subjects with a combination of low BMD and hearing impairment (44% in conductive and 35% in sensorineural) than those with high BMD and normal hearing (25%) ( P < 0·05). The duration of oestrogen deficiency was also longer in the former groups ( P < 0·05). Multivariate logistic regression analysis (adjusted for age and karyotype) showed that increased risk of fracture was independently associated with low BMD (OR 3·2, 95% CI: 1·0 to10·5) and hearing impairment (conductive: OR 4·8, 95% CI: 1·2 to18·9, sensorineural: OR 3·6, 95% CI: 1·1 to11·8). Subgroup analysis showed that hearing impairment was associated with fractures only in those with low BMD (OR 9·0, 95% CI: 1·1–73·4). Further adjustments for weight, height, BMI, calcium levels, vitamin D concentrations, thyroxine use and oestrogen deficiency, previous use of oxandrolone or GH did not alter these relationships. Conclusions Women with TS who have low BMD and hearing impairment, particularly a conductive type, are at increased risk of bone fractures. [ABSTRACT FROM AUTHOR]

The article focuses on the different methods doctors have for assessing (diagnosing) obesity in patients. The advantages and disadvantages of each method are discussed. A discussion of body mass indexing and waist circumference measurement, and their relationship to obesity assessment is presented. The clinical implications of obesity assessment are discussed.

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]

Objectives: To assess the impact of urinary incontinence (UI) on health outcomes over the entire spectrum of acute stroke severity (National Institutes of Health Stroke Scale [NIHSS] scores: 0–42), due to a paucity of data on patients with milder strokes. Patients and Methods: Data were prospectively collected (2014–2016) from the Sentinel Stroke National Audit Programme (1593 men, 1591 women; mean [SD] age 76.8 [13.3] years) admitted to four UK hyperacute stroke units (HASUs). Relationships between variables were assessed by multivariable logistic regression. Data were adjusted for age, sex, comorbidities, pre‐stroke disability and intra‐cranial haemorrhage, and presented as odds ratios with 95% confidence intervals. Results: Amongst patients with no symptoms or a minor stroke (NIHSS scores of 0–4), compared to patients without UI, patients with UI had significantly greater risks of poor outcomes including: in‐hospital mortality; disability at discharge; in‐hospital pneumonia; urinary tract infection within 7 days of admission; prolonged length of stay on the HASU; palliative care by discharge; activity of daily living (ADL) support, and new discharge to care home. In patients with more moderate stroke (NIHSS score of 5–15) the same outcomes were identified; being at greater risk for patients with UI, except for palliative care by discharge and ADL support. With the highest stroke severity group (NIHSS score of 16–48) all outcomes were identified except in‐patient mortality, pneumonia, and ADL support. However, odds ratios diminished as NIHSS scores increased. Conclusions: Urinary incontinence is a useful indicator of poor short‐term outcomes in older patients with an acute stroke, but irrespective of stroke severity. This provides valuable information to healthcare professionals to identify at‐risk individuals. [ABSTRACT FROM AUTHOR]

Provides information on a study regarding the effects of thiazolidinedione insulin-sensitizing treatment on total body fat and fat distribution of diabetic patients. Total body fat in underwater weighing; Abdominal fat measured by magnetic resonance imaging; Calculations of intra-abdominal and extra-abdominal adipose tissue and fat volumes.

Examines health and quality of life matters using federal guidelines in the United States for the identification of obesity. Lack of consistent published dat using standardized body mass index; Prevalence of cardiovascular risks in men and women; Difficulty in men and women in performing range of basic daily physical activities.

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: The present study assessed factors associated with the risk of surgical site infections (SSI) after a caesarean section (C-section). Methods: Data were collected in 1682 women undergoing elective (53.9%) and emergency (46.1%) C-sections between 1st August 2020, and 30th December 2021, at a National Health Service hospital (Surrey, UK). Results: At the time of C-section, the mean age was 33.1 yr (SD ± 5.2). Compared to women with BMI < 30 kg/m2, those with a BMI ≥ 35 kg/m2 had a greater risk of SSI, OR 4.07 (95%CI 2.48–6.69). Women with a history of smoking had a greater risk of SSI than those who had never smoked, OR 1.69 (95%CI 1.05–2.27). Women with a BMI ≥ 30 kg/m2 and had a smoking history or emergency C-section had 3- to tenfold increases for these adverse outcomes. Ethnic minority, diabetes or previous C-section did not associate with any of the outcomes. Conclusions: High BMI, smoking, and emergency C-section are independent risk factors for SSI from C-section. Women planning conception should avoid excess body weight and smoking. Women with diabetes and from ethnic minority backgrounds did not have increased risks of SSI, indicating a consistent standard of care for all patients. [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]

We measured rates of hospital admissions for mental health disorders and self‐poisoning during the pandemic in patients without COVID‐19, compared to those admitted before the pandemic. Data were collected from 01/04/2019 to 31/03/2021, including the pandemic period from 01/03/2020. There were 10 173 (47.7% men) from the pre‐pandemic and 11 019 (47.5% men) from the pandemic periods; mean age = 68.3 year. During the pandemic, admission rates for mental health disorders and self‐poisoning were higher for any given age and sex. Self‐poisoning was increased with toxic substances, sedatives and psychotropic drugs, but reduced with nonopioid analgesics. Patients admitted with mental health disorders had lower readmission rates within 28 days during the pandemic, but did not differ in other outcomes. Outcomes from self‐poisoning did not change between the two study periods. [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]

Objective: To reduce average surgical‐site infection (SSI) rates to less than 7.5%, as well as other complications by incrementally implementing an SSI prevention care bundle in maternity: (1) ChloraPrep; (2) PICO dressings, performing elective cesarean sections in a main theater rather than a labor ward and warming blankets; (3) vaginal cleansing; and (4) Hibiscrub. Methods: In this prospective cohort study, the association between categorical variables was assessed by χ2 tests, temporal trends in the monthly percentage change of SSI were measured using the Joinpoint Regression Program v4.7.0.0. Results: In all, 1682 women (mean age 33.1 ± 5.2 years) underwent either elective (53.9%) or emergency (46.1%) cesarean section. After a small initial increase (10.0%–11.8%), SSI progressively declined to 4.4% (χ2 = 22.1, P < 0.001), as did sepsis, reoperation or readmission for SSI: from 12.5% to 0.5% (χ2 = 90.1, P < 0.001). The rates of SSI fell progressively with the cumulative introduction care bundle components. The average monthly percentage change was −14.0% (95% confidence interval −21.8% to −5.4%, P = 0.004), and the average SSI rate was kept below 7.5% for the last 12 months of the study. Conclusion: The maternal SSI prevention care bundle is simple and inexpensive; it effectively reduces SSI after a cesarean section and should be offered routinely to women undergoing cesarean section. Synopsis: Global surgical‐site infection (SSI) rate relating to cesarean sections is up to 18%; no consensus of benchmark targets exists for SSI after cesarean section. [ABSTRACT FROM AUTHOR]

Objective: Socioeconomic and health inequalities persist in multicultural western countries. Here, we compared outcomes following an acute stroke amongst ethnic minorities with Caucasian patients. Methods: Data were prospectively collected (2014–2016) from the Sentinel Stroke National Audit Programme for 3309 patients who were admitted with an acute stroke in four UK hyperacute stroke units. Associations between variables were examined by chi-squared tests and multivariable logistic regression, adjusted for age, sex, prestroke functional limitations and co-morbidities, presented as odds ratios (OR) with 95% CI. Results: There were 3046 Caucasian patients, 95 from ethnic minorities (mostly South Asians, Blacks, mixed race and a few in other ethnic groups) and 168 not stated. Compared with Caucasian patients, those from ethnic minorities had a proportionately higher history of diabetes (33.7% vs 15.4%, P < 0.001), but did not differ in other chronic conditions, functional limitations or sex distribution. Their age of stroke onset was younger both in women (76.8 year vs 83.2 year, P < 0.001) and in men (69.5 year vs 75.9 year, P = 0.002). They had greater risk for having a stroke before the median age of 79.5 year: OR = 2.15 (1.36–3.40) or in the first age quartile (< 69 year): OR = 2.91 (1.86–4.54), requiring palliative care within the first 72 h: OR = 3.88 (1.92–7.83), nosocomial pneumonia or urinary tract infection within the first 7 days of admission: OR = 1.86 (1.06–3.28), and in-hospital mortality: OR = 2.50 (1.41–4.44). Conclusions: Compared with Caucasian patients, those from ethnic minorities had earlier onset of an acute stroke by about 5 years and a 2- to fourfold increase in many stroke-related adverse outcomes and death. [ABSTRACT FROM AUTHOR]

Hip fracture in older adults is associated with poor prognosis. We tested the hypothesis that a single standardized measure, pre-fracture mobility, can be used as an early indicator of patients at high health risk after a hip fracture. Analysis of prospectively collected data of older adults admitted with a hip fracture between April-2009 and June-2019 in a single NHS hospital, UK. Pre-fracture mobility status (freely mobile, mobilising outdoors with one aid or with two aids, and limited to indoors), was used to predict length of stay (LOS) and mortality in hospital, and discharge destination. Among 3073 (2231 women, 842 men) admitted from their own home (mean ± SD age = 82.7 ± 9.3 yr), 159 died and 2914 survived to discharge: 1834 back to their home, 772 to rehabilitation, 66 to residential care, 141 to nursing care and 101 to unknown destinations. Compared with LOS of 15.9 ± 15.6 days in patients who mobilised freely before fracture (reference), those who were able to mobilise outdoors with one aid stayed 3.5 days, and those with two aids or confined to indoor mobility stayed one week longer in hospital. In-patient mortality was increased among patients who mobilised outdoors with two aids: OR = 2.1 (95%CI = 1.3–3.3), and those limited to indoors: OR = 2.1 (1.3–1.5). Finally, a change in residence on discharge was more likely in those who mobilised outdoors with two aids (OR = 1.8, 95%CI = 1.2–2.6), and those limited to indoors (OR = 1.9, 95%CI = 1.2–2.9). In conclusion, pre-fracture mobility may be a useful early indicator for identifying patients at increased risk of adverse outcomes after an acute hip fracture. [ABSTRACT FROM AUTHOR]

Objective: Hospital-onset stroke (HOS) is associated with poorer outcomes than community-onset stroke (COS). Previous studies have variably documented patient characteristics and outcome measures; here, we compare in detail characteristics, management and outcomes of HOS and COS.Methods: A total of 1656 men (mean age ± SD = 73.1 years ± 13.2) and 1653 women (79.3 years ± 13.0), with data prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme, were admitted with acute stroke in four UK hyperacute stroke units (HASU). Associations between variables were examined by chi-squared tests and multivariable logistic regression (COS as reference).Results: There were 272 HOS and 3037 COS patients with mean ages of 80.2 years ± 12.5 and 76.4 years ± SD13.5 and equal sex distribution. Compared to COS, HOS had higher proportions ≥ 80 years (64.0% vs 46.4%), congestive heart failure (16.9% vs 4.9%), atrial fibrillation (25.0% vs 19.7%) and pre-stroke disability (9.6% vs 5.1%), and similar history of stroke, hypertension, diabetes, stroke type and severity of stroke. After age, sex and co-morbidities adjustments, HOS had greater risk of pneumonia: OR (95%CI) = 1.9 (1.3-2.6); malnutrition: OR = 2.2 (1.7-2.9); immediate thrombolysis complications: OR = 5.3 (1.5-18.2); length of stay on HASU > 3 weeks: OR = 2.5 (1.8-3.4); post-stroke disability: OR = 1.8 (1.4-2.4); and in-hospital mortality: OR = 1.8 (1.2-2.4), as well as greater support at discharge including palliative care: OR = 1.9 (1.3-2.8); nursing care: OR = 2.0 (1.3-4.0), help for daily living activities: OR = 1.6 (1.1-2.2); and joint-care planning: OR = 1.5 (1.1-1.9).Conclusions: This detailed analysis of underlying differences in subject characteristics between patients with HOS or COS and adverse consequences provides further insights into understanding poorer outcomes associated with HOS. [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]

The Blue Book published by the British Orthopaedic Association and British Geriatrics Society, together with the introduction of National Hip Fracture Database Audit and Best Practice Tariff, have been influential in improving hip fracture care. We examined ten-year (2009–2019) changes in hip fracture outcomes after establishing an orthogeriatric service based on these initiatives, in 1081 men and 2891 women (mean age = 83.5 ± 9.1 years). Temporal trends in the annual percentage change (APC) of outcomes were identified using the Joinpoint Regression Program v4.7.0.0. The proportions of patients operated beyond 36 h of admission fell sharply during the first two years: APC = − 53.7% (95% CI − 68.3, − 5.2, P = 0.003), followed by a small rise thereafter: APC = 5.8% (95% CI 0.5, 11.3, P = 0.036). Hip surgery increased progressively in patients > 90 years old: APC = 3.3 (95% CI 1.0, 5.8, P = 0.011) and those with American Society of Anaesthesiologists grade ≥ 3: APC = 12.4 (95% CI 8.8, 16.1, P < 0.001). There was a significant decline in pressure ulcers amongst patients < 90 years old: APC = − 17.9 (95% CI − 32.7, 0.0, P = 0.050) and also a significant decline in mortality amongst those > 90 years old: APC = − 7.1 (95% CI − 12.6, − 1.3, P = 0.024). Prolonged length of stay (> 23 days) declined from 2013: APC = − 24.6% (95% CI − 31.2, − 17.4, P < 0.001). New discharge to nursing care declined moderately over 2009–2016 (APC = − 10.6, 95% CI − 17.2, − 2.7, P = 0.017) and sharply thereafter (APC = − 47.5%, 95%CI − 71.7, − 2.7, P = 0.043). The rate of patients returning home was decreasing (APC = − 2.9, 95% CI − 5.1, − 0.7, P = 0.016), whilst new discharge to rehabilitation was increasing (APC = 8.4, 95% CI 4.0, 13.0; P = 0.002). In conclusion, the establishment of an orthogeriatric service was associated with a reduction of elapsed time to hip surgery, a progressive increase in surgery carried out on high-risk adults and a decline in adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Obesity, obstructive sleep apnoea (OSA) and hypertension frequently coexist and are associated with elevated cortisol levels. Identification and treatment of such patients is important when investigating for suspected Cushing's syndrome and hypertension. Studies of the impact of continuous positive airway pressure (CPAP) on cortisol and blood pressure are limited by the small sample size and show conflicting findings. We conducted a meta‐analysis to document changes in the levels of cortisol and blood pressure in response to CPAP treatment of OSA. Methods: Meta‐analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference for systolic (SBP) and diastolic blood pressure (DBP). The quality of the studies was evaluated using standard tools for assessing the risk of bias. Results: A total of 22 studies met our search criteria; they consisted of 16 prospective cohort studies (PCS) that recruited 385 participants and six randomized control trials (RCT) totalling 252 participants. The range of mean age was 41–62 years and BMI 27.2–35.1 kg/m2. CPAP treatment reduced plasma cortisol levels in PCS: SMD = −0.28 [95% confidence interval (95% CI) = −0.45 to −0.12], I2 = 0%, p =.79 and in RCT: SMD = −0.39 (95% CI = −0.75 to −0.03), I2 = 28.3%, p =.25. CPAP treatment reduced SBP by 5.4 mmHg (95% CI = 1.7–9.1) and DBP by 3.3 mmHg (95% CI = 1.0–5.7). Interstudy heterogeneity was low for all studies. Bias in most RCT arose from the lack of blinding of participants and personnel. Conclusion: CPAP treatment in individuals with OSA reduces cortisol levels and blood pressure. [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]

The Nottingham Hip Fracture Score (NHFS) has been developed for predicting 30-day and 1-year mortality after hip fracture. We hypothesise that NHFS may also predict other adverse events. Data from 666 patients (190 men, 476 women), aged 60.2–103.4 years, admitted with a hip fracture to a single centre from 1/10/2015 and 7/12/2017 were analysed. The ability of NHFS to predict mobility within 1 day after surgery, length of stay (LOS) find mortality, and discharge destination was evaluated by receiver operating characteristic curves and two-graph plots. The area under the curve (95% confidence interval [CI]) for predicting mortality was 67.4% (58.4–76.4%), prolonged LOS was 59.0% (54.0–64.0%), discharge to residential/nursing care was 62.3% (54.0–71.5%), and any two of failure to mobilise, prolonged LOS or discharge to residential/nursing care was 64.8% (59.0–70.6%). NHFS thresholds at 4 and 7 corresponding to the lower and upper limits of intermediate range where sensitivity and specificity equal 90% were identified for mortality and prolonged LOS, and 4 and 6 for discharge to residential/nursing care, which were used to create three risk categories. Compared with the low risk group (NHFS = 0–4), the high risk group (NHFS = 7–10 or 6–10) had increased risk of in-patient mortality: rates = 2.0% versus 7.1%, OR (95% CI) = 3.8 (1.5–9.9), failure to mobilise within 1 day of surgery: rates = 18.9% versus 28.3%, OR = 1.7 (1.0–2.8), prolonged LOS (> 17 days): rates = 20.3% versus 33.9%, OR = 2.2 (1.3–3.3), discharge to residential/nursing care: rates = 4.5% vs 12.3%, OR = 3.0 (1.4–6.4), and any two of failure to mobilise, prolonged LOS or discharge to residential/nursing care: rates = 10.5% versus 28.6%, 3.4 (95% CI 1.9–6.0), and stayed 4.1 days (1.5–6.7 days) longer in hospital. High NHFS associates with increased risk of mortality, prolonged LOS and discharge to residential/nursing care, lending further support for its use to identify adverse events. [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]

Summary: Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone–binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow‐up of 4.3 years. Patients: Three thousand three hundred sixty‐nine community‐dwelling men aged 40‐79 years from eight European centres. Measurements: Subjects were categorized according to baseline and follow‐up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27‐5.60)], erectile dysfunction [OR = 4.53 (2.05‐10.01)] and infrequent morning erections [OR = 3.40 (1.48‐7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT. [ABSTRACT FROM AUTHOR]

Introduction A wide variety of non-genetic and genetic factors have been shown to associate with increased risk for cerebral venous thrombosis (CVT). However, there is a paucity of risk factor data and conclusions about their impact are often conflicting. Herein, we quantified the associations of non-genetic and genetic risk factors for CVT in adults. Materials and methods Electronic databases were searched up to January 2017. Meta-analyses were performed (RevMan v5.3) to determine pooled odds ratios (ORs and 95% CIs) for risk factors, interstudy heterogeneity and publication bias. Results Twenty non-genetic ( n  = 2314) and 33 genetic ( n  = 2117) studies up to January 2017 met the selection criteria. For non-genetic factors, CVT risk increased in the presence of glucocorticosteroid therapy by 18.3-fold (3.3–102.6), alcohol consumption 2.7-fold (1.8–3.9), infection 7.5-fold (2.6–21.6), surgery 9.6-fold (1.1–83.5), hypercholesterolaemia 2.4-fold (1.3–4.4), hyperhomocysteinaemia 3.1-fold (2.1–4.6), antiphospholipid antibodies 7.0-fold (2.1–23.6), autoimmune diseases 5.6-fold (2.3–13.6), anaemia 4.0-fold (2.1–7.9), malignancy 3.2-fold (1.4–7.1) and pregnancy/puerperium 11.4-fold (5.7–24.3). Smoking, hypertension and diabetes did not associate with CVT risk. For genetic factors, CVT risk increased in the presence of factor V Leiden ( G1691A ) by 2.5-fold (1.9–3.3), protein C deficiency 10.7-fold (3.1–37.7), protein S deficiency 5.7-fold (1.4–22.4), antithrombin deficiency 3.8-fold (1.0–13.8), prothrombin ( G20210A ) 5.5-fold (4.0–7.27) and TAFI gene variant ( C1040T ) 1.6-fold (1.0–2.4). Prothrombin G20210A and factor V Leiden polymorphisms tended to have higher ORs for CVT than for ischaemic stroke. Conclusions We provide quantitative data supporting a strong basis for genetic and non-genetic risk factors in CVT. Its genetic liability seems higher when compared with sporadic ischaemic stroke. [ABSTRACT FROM AUTHOR]

Summary: Objective: Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). Design, Patients and Measurements: We conducted a 4.3‐year prospective observational study of 3369 community‐dwelling European men aged 40‐79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. Results: Age >70 years (OR = 4.12 [2.07‐8.20]), diabetes (OR = 2.86 [1.42‐5.77]), chronic pain (OR = 2.53 [1.34‐4.77]), predegree education (OR = 1.79 [1.01‐3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24‐4.50]) predicted development of HLH. Younger age (40‐49 years, OR = 8.14 [1.35‐49.13]) and nonsmoking (OR = 5.39 [1.48‐19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85‐43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. Conclusions: Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism. [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]

Objective: Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adults and children by analyzing mortality rates, neurologic outcomes, and adverse effects.Data Sources: Electronic databases PubMed, Google Scholar, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov and manual searches of studies were conducted for relevant publications up until February 2016.Study Selection: Forty-one studies in adults (n = 3,109; age range, 18-81 yr) and eight studies in children (n = 454; age range, 3 mo to 18 yr) met eligibility criteria.Data Extraction: Baseline patient characteristics, enrollment time, methodology of cooling, target temperature, duration of hypothermia, and rewarming protocols were extracted.Data Synthesis: Risk ratios with 95% CIs were calculated. Compared with adults who were kept normothermic, those who underwent therapeutic hypothermia were associated with 18% reduction in mortality (risk ratio, 0.82; 95% CI, 0.70-0.96; p = 0.01) and a 35% improvement in neurologic outcome (risk ratio, 1.35; 95% CI, 1.18-1.54; p < 0.00001). The optimal management strategy for adult patients included cooling patients to a minimum of 33°C for 72 hours, followed by spontaneous, natural rewarming. In contrast, adverse outcomes were observed in children who underwent hypothermic treatment with a 66% increase in mortality (risk ratio, 1.66; 95% CI, 1.06-2.59; p = 0.03) and a marginal deterioration of neurologic outcome (risk ratio, 0.90; 95% CI, 0.80-1.01; p = 0.06).Conclusions: Therapeutic hypothermia is likely a beneficial treatment following traumatic brain injuries in adults but cannot be recommended in children. [ABSTRACT FROM AUTHOR]

Objective In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone ( LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism ( PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men. Design, Patients and Measurements A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years. Men were classified as incident (i) PHG (eugonadal [ EUG, T ≥ 10·5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG ( PHG at baseline and follow-up), pEUG ( EUG at baseline and follow-up) and reversed (r) PHG ( PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models. Results Of 1,991 men comprising the analytical sample, 97·5% had pEUG, 1·1% iPHG, 1·1% pPHG and 0·3% rPHG. The incidence of PHG was 0·2%/year. Higher age (>70 years) [ OR 12·48 (1·27-122·13), P = 0·030] and chronic illnesses [ OR 4·24 (1·08-16·56); P = 0·038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance. Conclusions Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study. [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]