Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

OBJECTIVE: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. METHODS: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. RESULTS: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. CONCLUSIONS: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. TRIAL REGISTRATION NUMBER: (ISRCTN52480460); results.

A case of an avoidable admission to an Ebola treatment unit with malaria and an associated heat illness.

We present a 27-year old British nurse admitted to the Kerry Town Ebola Treatment Unit, Sierra Leone, with symptoms fitting suspect-Ebola virus disease (EVD) case criteria. A diagnosis of Plasmodium falciparum malaria and heat illness was ultimately made, both of which could have been prevented through employing simple measures not utilised in this case. The dual pathology of her presentation was atypical for either disease meaning EVD could not be immediately excluded. She remained isolated in the red zone until 72 h from symptom onset. This case highlights why force protection measures are important to reduce the incidence of both malaria and heat illness in deployed military and civilian populations. These prevention measures are particularly pertinent during the current EVD epidemic where presenting with these pathologies requires clinical assessment in the 'red zone' of an Ebola treatment unit.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN52480460.

The biochemical, physiological and psychological consequences of a "1,000 miles in 1,000 hours" walking challenge.

The combined effects of 42 days of chronic sleep disruption and repeated hourly bouts of physical exertion have not been described. This case study reports the physiological and psychological demands placed on one individual who walked 1 mile in each consecutive hour for a period of 1,000 h (42 days), covering a total distance of 1,000 miles. The participant walked at a mean speed of 1.75 m/s completing each mile in approximately 15 min. Over the course of the challenge, the individual lost 1.6 kg in body weight. Markers of skeletal muscle damage, increased gradually whilst free testosterone levels decreased over the course of the challenge. Stress hormones increased whilst inflammatory markers (CRP) initially rose but then returned towards baseline over the course of the study. Cognitive motor performance measured via reaction time was maintained throughout the 42 days. The participant also displayed mood states typical of an elite athlete at baseline and throughout the challenge. Participation in this novel '1,000 mile 1,000 h' walking challenge evoked considerable physiological stress in a fit, healthy middle-aged participant but did not markedly alter cognitive performance or mood over the 42-day period.

Undifferentiated febrile illnesses amongst British troops in Helmand, Afghanistan.

OBJECTIVES: Undifferentiated febrile illnesses have been a threat to British expeditionary forces ever since the Crusades. The infections responsible were identified during the Colonial Era, both World Wars and smaller conflicts since, but nearly all remain a significant threat today. Undiagnosed febrile illnesses have occurred amongst British troops in Helmand, Afghanistan since 2006 and so a fever study was performed to identify them. METHODS: From May to October 2008, all undifferentiated fever cases seen at the British field hospital in Helmand, Afghanistan were assessed using a standard protocol. Demographic details, clinical features and laboratory results were recorded and paired serum samples were sent for testing at the UK Special Pathogens Reference Unit (SPRU). RESULTS: Over 6 months, there were 26 cases of"Helmand Fever" assessed and 23 diagnoses were made of which 12 (52%) were sandfly fever, 6 (26%) were acute Qfever and 5 (22%) were rickettsial infections. Four cases had co-infections and 7 cases were not diagnosed (mostly due to inadequate samples). The clinical features and laboratory results available at the British field hospital did not allow these diseases to be distinguished from each other. The exact type of rickettsial infection could not be identified at SPRU. CONCLUSIONS: These cases probably represent the "tip of an iceberg" for British and Allied forces. More resources for diagnostic facilities and follow-up of patients are required to improve the management and surveillance of "Helmand Fever" cases; until then doxycycline 100 mg twice daily for 2 weeks should be given to all troops who present with an undifferentiated febrile illness in Helmand, Afghanistan. Patients with acute Q fever should be followed-up for at least 2 years to exclude chronic Q fever. Prevention of these diseases requires a better understanding of their epidemiology, but prophylaxis with doxycycline and possibly Q fever vaccine should be considered.

Gastrointestinal transit, post-prandial lipaemia and satiety following 3 days high-fat diet in men.

BACKGROUND/OBJECTIVES: High-fat (HF) diets of 2 weeks have been shown to accelerate gastric emptying (GE). To date, no studies have shown any alteration in GE following shorter HF diets. The aim of this study was to assess if an HF, high-energy diet of 3 days can adapt gastrointestinal (GI) transit, blood lipids and satiety. SUBJECTS/METHODS: Eleven male volunteers participated in a study consisting of three, 3-day interventions each separated by a test day. During the first intervention, volunteers recorded their diet. In the second and third interventions, volunteers repeated their food diary plus either a low-fat yogurt or HF yogurt supplement in randomized order. Test days involved measurement of GE using the (13)C octanoic-acid breath-test, mouth-to-caecum transit time (MCTT) using the inulin H(2) breath test and satiety using visual analogue scales. Blood samples for measurement of lipaemia were taken using a venous cannula. RESULTS: MCTT was different between the three test days (P=0.038), with the shortest MCTT following the HF intervention. GE was shortest following the HF intervention. There were no differences in satiety between the interventions. The HF intervention reduced triglycerides, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. CONCLUSION: This study shows that changes in GI transit owing to an HF diet can occur in a time period as short as 3 days.

Are the adverse effects of glitazones linked to induced testosterone deficiency?

BACKGROUND: Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested. PRESENTATION OF HYPOTHESIS: The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications. TESTING OF THE HYPOTHESIS: Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted. IMPLICATIONS OF THE HYPOTHESIS: Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.

The effects of ingesting a carbohydrate-electrolyte beverage 15 minutes prior to high-intensity exercise performance.

The aim of this study was to examine the effect of ingesting a commercially available carbohydrate-electrolyte (CHO-E) solution on strenuous exercise performance. Ten apparently healthy male volunteers (Mean +/- SD; age 20 +/- 2 yrs; height 178 +/- 7 cm; body mass 77 +/- 10 kg; estimated VO(2 max) 56 +/- 3 ml x kg(-1) x min(-1) completed three experimental trials in random order separated by a minimum of 7 days. For each trial, subjects consumed (8 ml x kg(-1) body mass) either a CHO-E solution (6% carbohydrate, 50 mg Na/500 ml), a non-CHO-E placebo, or no fluid, 15 minutes prior to exercise. The exercise involved intermittent shuttle (20 m apart) running for 1 hr followed by an incremental shuttle running test to exhaustion. Subjects displayed longer exercise times when the CHO-E solution was ingested compared with placebo or no fluid groups (exercise time to exhaustion - CHO-E 649 +/- 95 s, vs. placebo 601 +/- 83 s, vs. no fluid 593 +/- 107 s, P < 0.05). There was a main effect for time for specific gravity of urine (P < 0.05 vs. postexercise, pooled data) and body mass (P < 0.05 vs. postexercise, pooled data). The main finding from this investigation indicates that drinking a CHO-E solution 15 minutes prior to exercise improves performance. This study has practical implications for those sports where drinking during activity is restricted.

Measurement of serum albumin by capillary zone electrophoresis, bromocresol green, bromocresol purple, and immunoassay methods.

BACKGROUND/AIMS: The introduction of capillary zone electrophoresis (CZE) to this laboratory has highlighted discrepancies in albumin measured on an Abbott Aeroset by bromocresol green (BCG) and that calculated by CZE on the basis of total protein measured by Biuret. METHODS: This study examined differences in albumin estimation by CZE, Abbott Aeroset BCG, and Aeroset bromocresol purple (BCP), and compared these with albumin estimated by Beckman Array immunoassay. RESULTS: Altman and Bland analysis of results showed a positive bias of BCG with CZE (4.51 g/litre; 95% limits of agreement, 3.77 to 5.26; n = 72) and BCP (3.85 g/litre; 95% limits of agreement, -1.42 to 9.12; n = 72). CZE and BCP agreed closely (0.67 g/litre; 95% limits of agreement, -4.39 to 3.06; n = 72). Analysis of 57 of those samples in which BCG and CZE differed > or = 5 g/litre showed a positive bias of BCG with immunoassay (8.35 g/litre; 95% limits of agreement, 1.54 to 15.16; n =57), with good agreement between CZE and immunoassay (-0.44 g/litre; 95% limits of agreement, -2.82 to 1.94; n = 57). CONCLUSIONS: BCP is superior to BCG for the assay of albumin and has replaced BCG as the routine test for albumin in this laboratory.

Physical activity, physical fitness and respiratory function--exercise and respiratory function.

The aim of the study was to establish patterns of respiratory function in Northern Ireland and to examine the relationship between physical activity, physical fitness and respiratory function. We identified 1600 adults over 16 yr using 2 stage probability sampling. Physical activity was measured using a questionnaire, physical fitness from oxygen uptake while walking on a treadmill, and respiratory function using spirometry. The main outcome measures were a physical activity profile based on computer assisted interview, physical fitness by predicted VO2max, Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1). We found that the main findings were of relationships between activity and FVC and FEV 1 which remained after adjustment for possible confounders in men, and between fitness and FVC and FEV 1 in both men and women although these were not sustained after adjustment for possible confounders.

Levels of physical activity, physical fitness and their relationship in the Northern Ireland Health and Activity Survey.

The aim of the study was to describe the physical activity and physical fitness profile of the population of Northern Ireland and to explore the relationship between physical activity and physical fitness. This was a cross sectional population study using a two stage probability sample of the adult population of Northern Ireland (aged 16+). The main outcome measures were physical activity profile based on computer assisted interview. Physical fitness using estimation of VO2max by extrapolation from submaximal oxygen uptake while walking on a motor driven treadmill. We found that males were more vigorously active than females (M 21%:F 6%) with a steep gradient of decreasing activity with age: 49% (M 52%:F 46%) were regularly active up to at least moderate intensity. Males (mean predicted VO2max 44.4 mls/kg/min; 16-74 years) were fitter than females (mean predicted VO2max 34.0 mls/kg/min; 16-74 years) and while there was a decline in predicted VO2max with age, there was wide variation within each age category. There was no statistically significant relationship between current or past activity and fitness after adjustment for possible confounding factors, with the exception of a relationship between fitness and activity in males so that the difference between no activity and habitual vigorous activity in predicted VO2max was 4.4mls/kg/min (10.1%).

Physical fitness, lipids, and apolipoproteins in the Northern Ireland Health and Activity Survey.

The objective of this study was to investigate the relationship between physical fitness, lipids, and apolipoproteins in a cross-sectional study using a two-stage probability sample of the population of Northern Ireland. The main outcome measures were physical fitness using VO2max estimated by extrapolation from submaximal oxygen uptake while walking on a motor driven treadmill, and total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, HDL2 and HDL3, and Lp(a). There were no significant relationships with fitness, after adjustment for possible confounders, with the exception of a positive relationship with HDL2 in males (P < or = 0.01) and Lp(a) in females (P < or = 0.05). There was also a relationship between physical fitness and HDL:apo AI ratio in males and females after adjustment for possible confounders (P < or = 0.05). We concluded that there were few relationships between lipid parameters and physical fitness after adjustment for possible confounders. The relationship between physical fitness and Lp(a) in females suggests a benefit associated with physical fitness and the relationship between physical fitness and HDL:apo AI ratio was in keeping with improved HDL cholesterol transport.

APO E genotype and familial hypercholesterolaemia.

Apolipoprotein E genotypes were measured in 83 patients with familial hypercholesterolaemia (FH) and in 175 blood donor controls. Following DNA extraction from peripheral blood, each sample was genotyped for the Apo E polymorphism by polymerase chain reaction. No significant differences were found in the levels of the epsilon 2 and epsilon 3 alleles between the two groups, while the epsilon 4 allele was approximately twice as prevalent in the FH patients as in controls (P = 0.006, df = 1). Of the FH patients, 8.4% were homozygous for the epsilon 4 allele while this genotype was rare in controls (P = 0.009, df = 1). These results suggest that the epsilon 4 allele is over represented in the FH population and may contribute to increased cholesterol levels and consequent vascular disease.

Serum glutathione S-transferase concentrations and creatinine clearance after sevoflurane anaesthesia.

The effects of sevoflurane and isoflurane on serum glutathione S-transferase concentrations and creatinine clearance were compared in 50 ASA I-III patients aged over 18 years undergoing body surface surgery of 1-3 h predicted duration. Patients randomly received sevoflurane (n = 24) or isoflurane (n = 26) in nitrous oxide and oxygen (FIO2 = 0.4) via a nonrebreathing system. Fluids were standardised and patient's lungs ventilated to normocapnia. Expired concentration of anaesthetic agent was adjusted to maintain systolic arterial pressure between 70 and 100% of baseline. Patients received significantly less (p < 0.05) sevoflurane (1.0 MAC-h) than isoflurane (1.5 MAC-h). Using serum glutathione S-transferase concentrations and creatinine clearance as markers of hepatic and renal function respectively, no statistically significant differences were identified between the groups.

Physical activity, lipids, apolipoproteins, and Lp(a) in the Northern Ireland Health and Activity Survey.

In a cross-sectional study using a two-stage probability sample (N = 1,600) of the population of Northern Ireland, there was an inverse association between the highest recorded recent activity and total cholesterol (P < or = 0.01), LDL (P < or = 0.01), triglyceride (P < or = 0.05) and Chol:HDL ratio (P < or = 0.001) in males, and total cholesterol (P < or = 0.001), LDL (P < or = 0.001), and triglyceride (P < or = 0.01) in females; between habitual activity and HDL (P < or = 0.05) in males and total cholesterol (P < or = 0.05) and triglyceride (P < or = 0.01) in females. There was a relationship between the highest recorded activity and apoAI (P < or = 0.01) and apoB (P < or = 0.01) in males and with apoB (P < or = 0.001) in females; between habitual activity and apoAI (P < or = 0.01) and apoAII (P < or = 0.05) in males and apoB (P < or = 0.01) in females; between past activity and Lp(a) in females (P < or = 0.05). After adjustment for possible confounding factors, total cholesterol (P < or = 0.05) and LDL (P < or = 0.05) were unexpectedly higher in males who were active throughout life. Total cholesterol (P < or = 0.05) and LDL (P < or = 0.001) were higher in females with highest recorded activity and triglycerides lower (P < or = 0.05) in those habitually active. An association between highest recorded activity and apoAI (P < or = 0.01), and past activity and apoAI:apoB ratio (P < or = 0.05) was shown in males and in females, after adjustment, and between apoB (P < or = 0.05) and highest recorded activity.

Physical activity, physical fitness, blood pressure, and fibrinogen in the Northern Ireland health and activity survey.

STUDY OBJECTIVE: To investigate the relationship between physical activity, physical fitness, blood pressure, and fibrinogen. DESIGN: This was a cross sectional population study using a two stage probability sample. SETTING: Northern Ireland. PARTICIPANTS: A sample of 1600 subjects aged 16-74 years from the population of Northern Ireland. MAIN OUTCOME MEASURES: Physical activity profile from computer assisted interview using the Allied Dunbar national fitness survey scales. Physical fitness using estimation of VO2 max by extrapolation from submaximal oxygen uptake while walking on a motor driven treadmill. Systolic and diastolic blood pressure measured with a Hawksley random zero sphygmomanometer. Measurement of fibrinogen using the Clauss method. MAIN RESULTS: There were significant relationships between both current and past activity and blood pressure. These were of a magnitude that would have been clinically significant, but for the fact that, with the exception of the relationship between habitual activity and diastolic pressure (p = 0.03) and past activity and systolic pressure (p = 0.03) in men, they were not sustained after adjustment for the effect of age using analysis of variance. After adjustment for other potentially confounding factors using multiple regression, there was an inverse relationship between systolic blood pressure and past activity in men, so that those with a life-time of participation compared with a life-time of inactivity had a lower systolic blood pressure of 6 mmHg (p < 0.05). There was a highly significant (p < 0.001) inverse association between both systolic and diastolic blood pressure and physical fitness (VO2 max) which was not sustained after adjustment for possible confounding factors. There were relationships between fibrinogen and highest recorded activity (p < 0.001), habitual activity (p < 0.01), and past activity (p < 0.01) in men but no significant relationship in women. The relationship between fibrinogen and activity was no longer sustained after adjustment for possible confounding factors. There was a highly significant (p < 0.001) inverse relationship with physical fitness using VO2 max. This relationship was sustained after adjustment for possible confounding factors in both men (p < 0.05) and women (p < 0.001). CONCLUSIONS: There was a relationship between physical activity, physical fitness, and blood pressure but the relationship was greatly influenced by age. A reduction of 6 mmHg in systolic blood pressure associated with past activity is of clinical significance and supports the hypothesis that physical activity is of benefit in reducing cardiovascular risk. There was a lower level of fibrinogen in those who were most active but this relationship was not significant after adjustment for possible confounding factors. There was also a lower level of fibrinogen those who were most fit (VO2 max) and this relationship persisted even after adjustment for possible confounding factors.

Vitamin E and exercise in the Northern Ireland population.

Serum vitamin E, vitamin E/cholesterol and physical activity and fitness were examined in a representative cross section (n = 1600) of the Northern Ireland population as part of the Northern Ireland health and activity survey. Serum vitamin E levels were measured by high-performance liquid chromatography, cholesterol by an enzymatic method, physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max. The levels of serum vitamin E and vitamin E/cholesterol ratio in the Northern Irish population were similar or higher than in other populations with lower incidences of coronary heart disease. The assessment of activity showed that 75% of the population fell below recommended activity levels likely to confer a cardioprotective effect. A significant relationship (P = 0.01) was found in males between serum vitamin E levels and lifetime participation in physical activity. Otherwise no relationship was found between serum vitamin E or vitamin E/cholesterol ratio and physical activity or fitness in the population.