Christopher Boos

A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema (BOLT Study): 12-Month Data: Report 2

PURPOSE To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME). DESIGN Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial. PARTICIPANTS A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. METHODS Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). MAIN OUTCOME MEASURES The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms. RESULTS The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group. CONCLUSIONS The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.

Severe acute mountain sickness, brain natriuretic peptide and NT-proBNP in humans.

To examine the response of brain natriuretic peptide (BNP) and NT‐proBNP to high altitude (HA) both at rest and following exercise.

Self-administration of exercise and dietary supplements in deployed British military personnel during Operation TELIC 13.

Objectives Recent operational experience has led to the identification of several potentially serious adverse events related to the use of dietary and exercise supplements among British Army personnel. This study aimed to establish the point prevalence of dietary and exercise supplement usage in British soldiers on Op TELIC during January 2009. Methods A cross-sectional questionnaire-based study of British military personnel located at the Contingency Operating Base (COB), in Basra, was performed during the sixth week of Op TELIC 13. Results From 1544 questionnaires (target population) issued, a total of 1017 (65.9%) completed questionnaires were evaluated. The mean population age was 29.5 years (range 18-58) of which 87.4% were male. 417/1017 persons (41.0%) admitted to a history of supplement use of which 32.0% were current users and 9.4% were previous users. Of these current users, 66.0% started taking them on their current deployment. The most commonly taken supplements were whey protein (18.8%), amino acids (17.9%), and creatine (13.2%). There were 14 persons (1.4%) who admitted to current use of anabolic steroids. The most-frequently given reasons for taking supplements were either to ‘increase muscle bulk’ (40.4%) or to aid training and recovery (20.8%). Conclusions This is the first study to investigate the use of exogenous nutritional supplements within the British Military and has identified their widespread use during operational deployment. The use of anabolic steroids is particularly worrying, given both their illegality and their well-recognised and deleterious health effects. There is a need for greater awareness and education regarding potential benefits and dangers of supplement use in order to maximise any potential benefits and minimise clinical risk.

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude

Background There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses. Materials and Methods This was a prospective observational study of 14 healthy subjects aged 22–35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA. Results All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise. Conclusions GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function.

A comparison of substrate oxidation during prolonged exercise in men at terrestrial altitude and normobaric normoxia following the coingestion of 13C glucose and 13C fructose

This study compared the effects of coingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to altitude (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min−1 of glucose (enriched with 13C glucose) and 0.6 g·min−1 of fructose (enriched with 13C fructose) directly before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. Total carbohydrate oxidation during the exercise period was lower at altitude (157.7 ± 56.3 g) than sea level (286.5 ± 56.2 g, P = 0.006, ES = 2.28), whereas fat oxidation was higher at altitude (75.5 ± 26.8 g) than sea level (42.5 ± 21.3 g, P = 0.024, ES = 1.23). Peak exogenous carbohydrate oxidation was lower at altitude (1.13 ± 0.2 g·min−1) than sea level (1.42 ± 0.16 g·min−1, P = 0.034, ES = 1.33). There were no differences in rates, or absolute and relative contributions of plasma or liver glucose oxidation between conditions during the second hour of exercise. However, absolute and relative contributions of muscle glycogen during the second hour were lower at altitude (29.3 ± 28.9 g, 16.6 ± 15.2%) than sea level (78.7 ± 5.2 g (P = 0.008, ES = 1.71), 37.7 ± 13.0% (P = 0.016, ES = 1.45). Acute exposure to altitude reduces the reliance on muscle glycogen and increases fat oxidation during prolonged cycling in men compared with sea level.

The Hearts of Heroes: the epidemiology of cardiac disease in the UK Armed Forces

When the general public look from the outside at the armed services, their impression is often one of earnest young men and women who are the pinnacle of physical fitness and health, and put their lives on the line for their country. There is usually sadness and respect for those killed on active operations, having put themselves in harms way. Therefore, when the public discover that more than 1 in 10 deaths in the UK Armed Forces are due to cardiovascular disease, the air of sadness is invariably replaced with surprise and disbelief. These figures, while lower than those due to deaths in accidents, are approaching the numbers of those due to suicide in the armed services; yet deaths from cardiac disease are barely recognised by society, in spite of many of them being avoidable. This article reviews the epidemiology of cardiac disease in the UK Armed Forces, both in terms of morbidity and mortality. It outlines current understanding and gaps in the knowledge regarding the burden of cardiovascular disease in the military population. The particular demographics of the Armed Forces and its influence on cardiac disease burden are discussed. The role of inherited and congenital diseases in younger servicemen and women is highlighted, as is the trend that with increasing age, the burden of disease shifts to ischaemic heart disease, which becomes the dominant cause of both death and disability.

Back pain in a Bangladeshi worker in Iraq.

Pyogenic Spinal Infection (PSI) is an uncommon disorder encompassing a broad spectrum of diseases including septic spondylodiscitis, osteomyelitis, epidural and paravertebral abscess formation. Presentation can be vague and highly variable but usually includes back pain and fever. Whilst predisposing factors, such as trauma and diabetes can often be identified a pathogenic organism may not be identified in up to a half of all cases leading to significant delay in both accurate diagnosis and effective treatment. Precise spinal imaging is essential and includes plain X-ray, CT and preferably MRI. The treatment of PSI can be conservative (including antibiotics); however, spinal surgery may be required for the complications in up to 50% of cases, with varying degrees of success. We present a challenging case of PSI encountered in a locally-employed 42 year-old Bangladeshi civilian working in Iraq. Despite obvious resource limitations available within a Role 2 Field Hospital, clinical suspicion coupled with repeat spinal CT was pivotal in obtaining the diagnosis. The patient was repatriated to Bangladesh for MRI and definitive surgical treatment.

Ivabradine in heart failure: what about digoxin?

www.thelancet.com Vol 372 December 20/27, 2008 2113 results should not be used to discourage infl uenza vaccination in this popu lation. Never theless, our observations sug gest that previous non-randomised studies have probably overestimated the bene fi ts of infl uenza vaccination in elderly people, and that more work is needed to better protect these in di viduals from infl uenza-related complications. Thijs and Knottnerus raise some concerns about our study’s methods, which we address here. First, the high coverage of pneumococcal polysaccharide vaccine in our study population is unlikely to have aff ected our estimates of infl uenza vaccine eff ectiveness. Evidence suggests that, although pneumococcal polysaccharide vaccine might reduce the risk of invasive pneumococcal disease in seniors, it does not reduce the risk of pneumonia more generally and so will not aff ect the association between infl uenza vaccination and risk of pneumonia to any important degree. Second, the possible misclassifi cation of pneumonia deaths is probably of little concern in this study. Because we excluded seniors with conditions such as serious cancer, the death rate in our source cohorts was (relatively) low, at 1·47 deaths per 100 person-years. Misclassifi cation of pneumonia among those who died is an unlikely explanation for our fi ndings. Finally, the eff ect of previous infl uenza vaccination on infl uenza vaccine eff ectiveness is an important sub ject for future study. However, un like previous studies of infl uenza vaccination in seniors, we showed that our ad justment methods could produce the expected true association during preinfl uenza periods, as shown by the pre infl uenza relative risk of 1·0. Thus, over adjustment (or underadjustment) for any baseline health characteristics ought not to be of concern.