Pain after combat injury in male UK military personnel deployed to Afghanistan.

BACKGROUND: Chronic pain after injury poses a serious health burden. As a result of advances in medical technology, ever more military personnel survive severe combat injuries, but long-term pain outcomes are unknown. We aimed to assess rates of pain in a representative sample of UK military personnel with and without combat injuries. METHODS: We used data from the ADVANCE cohort study (ISRCTN57285353). Individuals deployed as UK armed forces to Afghanistan were recruited to include those with physical combat injuries, and a frequency-matched uninjured comparison group. Participants completed self-reported questionnaires, including 'overall' pain intensity and self-assessment of post-traumatic stress disorder, anxiety, and depression. RESULTS: A total of 579 participants with combat injury, including 161 with amputations, and 565 uninjured participants were included in the analysis (median 8 yr since injury/deployment). Frequency of moderate or severe pain was 18% (n=202), and was higher in the injured group (n=140, 24%) compared with the uninjured group (n=62, 11%, relative risk: 1.1, 95% confidence interval [CI]: 1.0-1.2, P<0.001), and lower in the amputation injury subgroup (n=31, 19%) compared with the non-amputation injury subgroup (n=109, 26%, relative risk: 0.9, 95% CI: 0.9-1.0, P=0.034). Presence of at least moderate pain was associated with higher rates of post-traumatic stress (RR: 3.7, 95% CI: 2.7-5.0), anxiety (RR: 3.2, 95% CI: 2.4-4.3), and depression (RR: 3.4, 95% CI: 2.7-4.5) after accounting for injury. CONCLUSION: Combat injury, but not amputation, was associated with a higher frequency of moderate to severe pain intensity in this cohort, and pain was associated with adverse mental health outcomes.

ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study.

INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences.

A Double-Blind Placebo-Controlled Crossover Study of the Effect of Beetroot Juice Containing Dietary Nitrate on Aortic and Brachial Blood Pressure Over 24 h.

Dietary inorganic nitrate in beetroot can act as a source of nitric oxide and has been reported to lower brachial blood pressure (BP). This study examined the effect of inorganic nitrate in beetroot juice on aortic (central) BP acutely and over the subsequent 24-h period. A double blind, randomized, placebo-controlled crossover trial was performed in fifteen healthy, normotensive men and women (age 22-40 years). Participants were randomized to receive beetroot juice containing nitrate (6.5-7.3 mmol) or placebo beetroot juice from which nitrate had been removed (<0.06 mmol nitrate). Effects on aortic systolic BP were measured at 30 min (primary endpoint), 60 min and over a subsequent 24 h period using an ambulatory BP monitor. Carotid-femoral pulse wave velocity (cfPWV) was also measured at 30 min. Following a washout period, the procedure was repeated within 7 days with crossover to the opposite arm of the trial. Compared with placebo, ingestion of beetroot juice containing nitrate lowered aortic systolic BP at 30 min by 5.2 (1.9-8.5) mmHg [mean (95% confidence interval); p < 0.01]. A smaller effect on aortic systolic BP was observed at 60 min. There were minimal effects on brachial BP or cfPWV. Effects on aortic systolic BP were not sustained over the subsequent 24 h and there were no effects on other hemodynamic parameters during ambulatory monitoring. A single dose of beetroot juice containing nitrate lowers aortic BP more effectively than brachial BP in the short term, but the effects are comparatively short-lived and do not persist over the course of the same day.

Assessment of Exercise Capacity and Oxygen Consumption Using a 6 min Stepper Test in Older Adults.

It is often necessary to assess physical function in older adults to monitor disease progression, rehabilitation or decline in function with age. However, increasing frailty and poor balance that accompany aging are common barriers to exercise testing protocols. We investigated whether a 6-min stepper test (6MST) was acceptable to older adults and provided a measure of exercise capacity and a predicted value for peak aerobic capacity (VO2max). 635 older adults from a tri-ethnic UK population-based cohort were screened to undertake a self-paced 6MST. Expired gas analysis, heart rate and blood pressure monitoring were carried out. A sub-set of 20 participants performed a second 6MST for assessment of reproducibility and a further sub-set of 10 performed the 6-min walk test as verification against a well-recognized and accepted self-paced exercise test. 518 (82%) participants met inclusion criteria and undertook the 6MST (299 men, mean age 71.2 ± 6.4). Step rate showed a strong positive correlation with measured VO2 (r = 0.75, p < 0.001) and VO2 was lower in women (male-female difference in VO2 = 2.61 (95% confidence interval -3.6, -1.7) ml/min/kg; p < 0.001). 20 participants repeated a 6MST, step rate was higher in the second test but the predicted VO2max showed good agreement (mean difference = 0.1 [3.72, 3.95] ml/min/kg). In 10 participants who completed a 6MST and a 6-min walk test there was a strong positive correlation between walking rate and step rate (r = 0.77; p < 0.009) and weaker positive correlations between the tests for measured VO2 and peak heart rate. In conclusion, the 6MST is a convenient, acceptable method of assessing exercise capacity in older adults that allows VO2max to be predicted reproducibly. The test shows good correlation between performance and measured physiological markers of performance and can detect the expected gender differences in measured VO2. Furthermore, the 6MST results correlate with a previously verified and established self-paced exercise test.

A feasibility study of the association of exposure to biomass smoke with vascular function, inflammation, and cellular aging.

BACKGROUND: Biomass smoke at higher concentrations is associated with respiratory symptoms and, after years of exposure, increased risk of respiratory disorders in adults, but its effects on cardiovascular diseases are not well characterized, particularly compared with other pollution sources like tobacco smoke or traffic. METHODS: We conducted a cross-sectional study and enrolled 25 women living in rural Sichuan, China. We measured integrated 24-h personal exposure to fine particulate matter (PM2.5) and black carbon, and measured PM2.5 and black carbon in their kitchens. We assessed participants' brachial and central blood pressure and arterial stiffness using pulse wave analysis, and analyzed dried blood spot and buccal cell samples for C-reactive protein and relative telomere length. We also evaluated the difference in these physiological and biomarker measures between individuals with high (≥median) versus low (

British randomised controlled trial of AV and VV optimization ("BRAVO") study: rationale, design, and endpoints.

BACKGROUND: Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources. METHODS/DESIGN: BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014. DISCUSSION: If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented. TRIAL REGISTRATION: Clinicaltrials.gov NCT01258829.

Left-ventricular structure in the Southall And Brent REvisited (SABRE) study: explaining ethnic differences.

Cardiometabolic risk is elevated in South Asians and African Caribbeans compared with Europeans, yet whether this is associated with ethnic differences in left-ventricular structure is unclear. Conventional M-mode or 2-dimensional echocardiography may be misleading, because they calculate left-ventricular mass and remodeling using geometric assumptions. Left-ventricular structure was compared in a triethnic population-based cohort using conventional and 3-dimensional echocardiography on 895 individuals (aged 55-85 years; 427 European, 325 South Asian, 143 African Caribbean). Left-ventricular mass was indexed, and left-ventricle remodeling index and relative wall thickness were calculated. Anthropometry, blood pressure, and fasting bloods were measured. Three-dimensional left-ventricular mass index did not differ between Europeans (mean ± SE, 29.8 ± 0.3 g/m(2.7)) and African Caribbeans (29.9 ± 0.5 g/m(2.7); P=0.9), but it was significantly lower in South Asians (28.1 ± 0.4 g/m(2.7); P<0.0001) compared with Europeans. These findings persisted on multivariate adjustment. In contrast, conventional left-ventricle mass index was significantly higher in African Caribbeans (46.4 ± 0.9 g/m(2.7)) than in Europeans (41.9 ± 0.5 g/m(2.7); P<0.0001). Left-ventricle remodeling index was the highest in African Caribbeans and the lowest in South Asians. Relative wall thickness was also higher in African Caribbeans, but no different in South Asians, compared with Europeans. Differences in left-ventricle remodeling index were attenuated by adjustment for cardiometabolic factors between African Caribbeans and Europeans only. In conclusion, left-ventricular mass is lower in South Asians and equivalent in African Caribbeans compared with Europeans, even when cardiometabolic risk factors are accounted for. Left-ventricular remodeling rather than hypertrophy may explain the increased risk of heart failure in people of African Caribbean origin.

A randomized placebo controlled double blind crossover study of pioglitazone on left ventricular diastolic function in type 2 diabetes.

BACKGROUND/OBJECTIVES: Thiazolidinediones (TZDs), such as pioglitazone, are widely used to treat type 2 diabetes but there is evidence that their use is associated with an increased risk of heart failure. We compared the effect of pioglitazone vs. placebo on left ventricular (LV) diastolic and systolic function in people with type 2 diabetes. METHODS AND RESULTS: 24 male or female patients with type 2 diabetes were randomized to pioglitazone (45 mg/day) or placebo in addition to current therapy for 12 weeks using a prospective double blind crossover protocol following a run-in period >1 week and a 2 week washout period at crossover. Tissue Doppler early peak velocity (e'), a measure of LV diastolic function, was the primary outcome. Pioglitazone significantly increased e' by 0.7(0.1, 1.3) cm/s (mean (95% confidence interval); p=0.02) compared with placebo. Pioglitazone also increased E/A and mitral deceleration index, ejection fraction, stroke volume and weight, whereas fasting glucose, HbA1c, total peripheral resistance and LV meridional end systolic stress were decreased. CONCLUSIONS: Treatment with pioglitazone for 12 weeks improves left ventricular diastolic and systolic function in people with type 2 diabetes.

Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors.

BACKGROUND: Chronic hepatitis C (HCV) infection is associated with diabetes and favourable lipids. OBJECTIVE: To study the effect of this paradox on atherosclerosis and cardiometabolic response to HCV clearance. DESIGN: Cross-sectional study. SETTING: Egypt. PARTICIPANTS: 329 chronically infected, 173 with cleared infection and 795 never infected participants aged >or=35 attended for baseline investigations. A subsample of 192, 115 and 187, respectively, underwent ultrasound. MAIN OUTCOME MEASURES: Diabetes, fasting glucose, lipids and fat deposition on ultrasound. Carotid intima-media thickness (IMT) measured atherosclerosis. RESULTS: Diabetes prevalence was raised (10.1% (95% CI 6.6 to 13.6), p=0.04) in HCV chronic, and cleared (10.1% (5.6 to 14.8), p=0.08) individuals versus 6.6% (4.9 to 8.3) in those never infected. Mesenteric fat was raised in chronic (36.4 mm (34.5 to 38.2), p=0.004), and cleared infection (37.8 (35.6 to 40.0), p<0.0001) vs never infected (32.7 (31.0 to 34.4)). LDL cholesterol was lower in chronic (2.69 mmol/l (2.53 to 2.86), p<0.001), but similar in cleared (3.56 (3.34 to 3.78), p=0.4) versus never infected (3.45 (3.30 to 3.60)). Carotid IMT did not differ by infection status: 0.73 (0.70 to 0.76, p=0.4), 0.71 (0.66 to 0.75, p=0.9), 0.71 (0.68 to 0.74), respectively. Adjustment for cardiovascular risk factors increased IMT in chronic infection (0.76 (0.72 to 0.79), p=0.02) versus never infected individuals (0.70 (0.67 to 0.73)). CONCLUSIONS: Hepatic function normalisation with HCV clearance may account for reversal of favourable lipids observed with HCV infection. Hyperglycaemia and visceral adiposity appear less amenable to HCV resolution. These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status. However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection.

South Asian men have different patterns of coronary artery disease when compared with European men.

BACKGROUND: To compare patterns of coronary artery disease in British South Asian and White European men. METHODS: 41 South Asian and 42 European men (mean age 64+/-9 years) with coronary artery disease were studied. All had similar symptoms. Vessel reference diameter and degree of stenosis were calculated using quantitative coronary angiography. Extent of atherosclerotic disease in the LAD was assessed using calcification scores (CAC) measured by multislice Computed Tomography. Fasting bloods and blood pressure were measured. The LAD was subdivided into four 2.5 cm segments for analysis. RESULTS: Most atherosclerosis occurred in the proximal LAD segment, South Asian men had more proximal LAD stenosis than European men (50% vs. 37%, p=0.036), but CAC scores were similar. South Asians with CAC scores in the lowest tertile (0-22 HU), had significantly narrower LAD diameters than Europeans (2.8 mm vs. 3.8 mm, p=0.004, adjusted for body surface area and age). This ethnic difference was not explained by measured risk factors, including diabetes. In contrast, ethnic differences in LAD diameter were abolished in the upper tertiles of CAC scores (23-2416 HU) (South Asians: 3.0 mm, Europeans: 3.1 mm, p=0.6). Calcification scores were negatively correlated with LAD diameter in Europeans (rho=-0.38, p=0.016) but not in South Asians (rho=-0.06, p=0.72). CONCLUSIONS: Increased LAD stenosis, despite equivalent levels of calcified disease, in South Asians is attributable to narrower arteries. Reduced LAD diameter is associated with advanced disease in Europeans but not in South Asians, indicative of ethnic differences in vascular remodelling.

Measurement of pulse wave velocity: site matters.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts mortality from cardiovascular disease, ischaemic heart disease and stroke. However, a comparison of associations between PWV measured at different sites and atherosclerosis in coronary, carotid and femoral arteries has not been made. METHODS: In 159 men (ages 45-82 years) with and without known coronary artery disease, PWV measurements were made between carotid-femoral, carotid-radial and femoral-posterior tibial sites, using an ultrasound technique. Coronary artery calcification (CAC) scores were measured by multislice computed tomography. Carotid and femoral intima-media thickness (IMT) and presence of plaque were determined by ultrasound. Known coronary artery disease was confirmed by angiography. Participants were grouped into four categories of CAC score: 0-10, 11-100, 101-400, > 400 Hounsfield Units (HU). Measurements of blood pressure, heart rate and fasting bloods were made in all individuals. RESULTS: Carotid-femoral PWV correlated positively with CAC score and increased with incremental coronary calcification category (median carotid-femoral PWV 16.8 m/s in those with CAC score > 400 HU and 13.8 m/s in those with CAC score < 10 HU; P = 0.003). Carotid-femoral PWV also correlated with carotid and femoral IMT (P < 0.001, P = 0.004, respectively) and with carotid and femoral plaque (P = 0.001, P = 0.038, respectively). Increased carotid-femoral PWV also correlated with increasing age (P < 0.001), systolic blood pressure (P < 0.001), mean arterial pressure and pulse pressure (P < 0.001). Carotid-radial and femoral-posterior tibial PWV were not significantly associated with CAC score, carotid or femoral IMT or carotid plaque. CONCLUSIONS: Carotid-femoral PWV is a better indicator of atherosclerosis than either carotid-radial or femoral-posterior tibial PWV, and should be used preferentially in studies of atherosclerosis and in stratifying risk in clinical settings.

Indian Asian men have less peripheral arterial disease than European men for equivalent levels of coronary disease.

OBJECTIVES: Indian Asians have high rates of heart disease and stroke, but risks of peripheral arterial disease appear to be low. This paradox, and reasons for it, have not been explored. We compared ethnic differences in peripheral arterial disease for a given level of coronary disease. METHODS: We studied 83 European and 84 Indian Asian men with a range of coronary disease. Extent of coronary atheroma was quantified by coronary artery calcification score on multislice CT. Femoral intima-media thickness (IMT) was measured by ultrasound. RESULTS: Femoral IMT was 1.58, 2.06, 2.12, and 2.69 mm in Europeans, and 0.61, 1.41, 1.81 and 2.29 in Indian Asians by increasing categories of coronary atheroma (p=0.003 for ethnic difference, adjusted for age and lumen diameter). Adjustment for smoking and systolic blood pressure, the only risk factors adversely distributed in Europeans, only partly accounted for this ethnic difference (p=0.05). Other risk factors, including lipids, obesity, insulin and glycaemic status, more adversely distributed in Indian Asians, could not account for ethnic differences. Prevalence of abnormal ankle brachial index and lower limb atherosclerotic plaque was also greater in Europeans. CONCLUSIONS: For a given level of coronary disease, Indian Asians have less lower limb atherosclerosis than Europeans, unexplained by established risk factors. Further study of these populations would help tease out relative contributions of risk factors to atherosclerosis in different vessel beds.

Sistematizacion y evaluacion de intervenciones en servicios integrales de salud sexual y salud reproductiva: para mujeres, adolescentes y gente joven en la region andina con un enfoque de derechos e interculturalidad / s

Antecedentes. Poblacion y Area Geografica. Temas abordados en los Mini proyectos. Estrategias de intervencion. Resultados por Areas. Anexos

Sistematizacion y evaluacion de intervenciones en servicios integrales de salud sexual y salud reproductiva: para mujeres, adolescentes y gente joven en la region andina con un enfoque de derechos e interculturalidad / s

Antecedentes. Poblacion y Area Geografica. Temas abordados en los Mini proyectos. Estrategias de intervencion. Resultados por Areas. Anexos