Remote physiological monitoring in an austere environment: a future for battlefield care provision?

Wearable technologies are making considerable advances into the mainstream as they become smaller and more user friendly. The global market for such devices is forecasted to be worth over US$5 billion in 2018, with one in six people owning a device. Many professional sporting teams use self-monitoring to assess physiological parameters and work rate on the pitch, highlighting the potential utility for military command chains. As size of device reduces and sensitivity improves, coupled with remote connectivity technology, integration into the military environment could be relatively seamless. Remote monitoring of personnel on the ground, giving live updates on their physiological status, would allow commanders or medical officers the ability to manage their soldiers appropriately and improve combat effectiveness. This paper explores a proof of concept for the use of a self-monitoring system in the austere high altitude environment of the Nepalese Himalayas, akin to those experienced by modern militaries fighting in remote locations. It also reviews, in part, the historical development of remote monitoring technologies. The system allowed for physiological recordings, plotted against GPS position, to be remotely monitored in Italy. Examples of the data recorded are given and the performance of the system is discussed, including limitations, potential areas of development and how systems like this one could be integrated into the military environment.

Global lessons: developing military trauma care and lessons for civilian practice.

The wars in Iraq and Afghanistan have helped to shape the modern Defence Medical Services. Many lessons were learnt including the need for rapid haemorrhage control, senior decision-making and the evolution of deployed transfusion support. These changes were implemented simultaneously with a coherent, end-to-end medical plan from point of wounding through to rehabilitation. Implementation of the medical plan is harmonious with the NHS trauma pathway, and is key to ensuring effective delivery. Military anaesthetists have a long pre-deployment training pathway starting with a Certificate of Completion of Training (CCT) in anaesthesia and/or critical care, and with an emphasis on military skills related to their specific role. Pre-deployment training includes additional skill training, team training and finally whole hospital collective training. This pathway ensures ongoing and continuing competence on an individual basis, and assurance that hospital management systems and clinical staff can function effectively as a deploying unit.

Military Anaesthesia in contingencies: what skill sets are required and how will we prepare our trainees?

The Defence Medical Services are now in an established period of contingency operations. In 2008, the Royal College of Anaesthetists approved a Military Anaesthesia Higher Training Module which could be easily achieved by deploying to the field hospital in Camp Bastion, Afghanistan, for two months under the supervision of a consultant anaesthetist. This opportunity no longer exists but the need to assure quality training and to demonstrate military skill sets is still essential. This article discusses the revised Military Higher Module and how it will be implemented in the future either during deployment or during times of peace.

Education and Ebola: initiating the cascade of emergency healthcare training.

In response to the 2014 Ebola virus outbreak in West Africa, the UK deployed a Joint Inter-Agency Task Force to Sierra Leone. As well as constructing Ebola treatment units, the force supported a rapidly upscaled mass programme of training for host nation healthcare workers in basic knowledge of Ebola and personal protective equipment. A bespoke training course was developed in collaboration with the WHO and other partners over a period of 2 weeks, taught to 119 trainers the following week, and then cascaded to over 4000 Ebola workers over the following month. This article describes curriculum design, content delivery and assessment of this unique Training The Trainers course delivered in austere circumstances. Key learning points are highlighted and supplementary material is provided to inform future deployed clinical education initiatives.

Bending the curve: force health protection during the insertion phase of the Ebola outbreak response.

After >10 years of enduring operations in Iraq and Afghanistan, Defence Strategic Direction is returning to a contingency posture. As the first post-Afghanistan operation, in September 2014, a UK Joint Inter-Agency Task Force deployed to Sierra Leone in response to the Ebola virus disease (EVD) epidemic in West Africa. The aims were expanding treatment capacity, assisting with training and supporting host nation resilience. The insertion phase of this deployment created a unique set of challenges for force health protection. In addition to the considerable risk of tropical disease and trauma, deployed personnel faced the risks of working in an EVD epidemic. This report explores how deployed medical assets overcame the difficulties of mounting a short-notice contingent operation in a region of the world with inherent major climatic and health challenges.

The 2014 West Africa Ebola crisis: lessons from UK Defence Healthcare Engagement in Sierra Leone.

The 2014 West Africa Ebola virus disease outbreak prompted the deployment to Sierra Leone of non-governmental organisations and the UK Joint Inter-Agency Taskforce including personnel from the UK Defence Medical Services (DMS). Some of these military personnel partnered with the Republic of Sierra Leone Armed Forces (RSLAF) as an example of Defence Healthcare Engagement (DHE).UK DMS mentors assisted RSLAF to plan and upscale Ebola treatment units. Use of military analysis and planning tools facilitated robust and flexible plans to be produced while under significant time and resource constraints. Macrosimulation exercises enabled large numbers to be trained and standard operating procedures to be developed.Fundamental to success was a mutual respect between the DHE partners while maintaining host nation primacy throughout. DHE in this example offered advantages over non-governmental organisations. Transferable lessons for future DHE from the RSLAF-UK DMS partnership are described in this paper.

Screening for gestational diabetes mellitus: cost-utility of different screening strategies based on a woman's individual risk of disease.

AIMS/HYPOTHESIS: The cost-effectiveness of eight strategies for screening for gestational diabetes (including no screening) was estimated with respect to the level of individual patient risk. METHODS: Cost-utility analysis using a decision analytic model populated with efficacy evidence pooled from recent randomised controlled trials, from the funding perspective of the National Health Service in England and Wales. Seven screening strategies using various combinations of screening and diagnostic tests were tested in addition to no screening. The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY) over a lifetime. RESULTS: The strategy that has the greatest likelihood of being cost-effective is dependent on the risk of gestational diabetes mellitus for each individual woman. When gestational diabetes mellitus risk is <1% then the no screening/treatment strategy is cost-effective; where risk is between 1.0% and 4.2% fasting plasma glucose followed by OGTT is most likely to be cost-effective; and where risk is >4.2%, universal OGTT is most likely to be cost-effective. However, acceptability of the test alters the most cost-effective strategy. CONCLUSIONS/INTERPRETATION: Screening for gestational diabetes can be cost-effective. The best strategy is dependent on the underlying risk of each individual and the acceptability of the tests used. The current study suggests that if a woman's individual risk of gestational diabetes could be accurately predicted, then healthcare resource allocation could be improved by providing an individualised screening strategy.

Anaesthetic and critical care management of thoracic injuries.

Thoracic wounding has been a relatively common presentation of military wounds throughout modern conflict. When civilian casualties are included the incidence has remained constant at around 10%, although the frequency and severity of wounds to combatants has been altered by modern body armour. Whilst thoracic injury has a high initial mortality on the battlefield, those surviving to reach hospital frequently have injuries that only require simple management. In addition to penetrating ballistic injury, blunt chest trauma frequently occurs on operations as a result of road traffic collisions or tertiary blast injury. The physiological impact of thoracic wounds, however, is often great and survivors often require intensive care management and, where available, complex strategies to ensure oxygenation and carbon dioxide removal. This review examines the incidence and patterns of thoracic trauma and looks at therapeutic options for managing these complex cases.

Early N-terminal pro-brain natriuretic peptide measurements predict clinically significant ductus arteriosus in preterm infants.

UNLABELLED: We report a blinded, prospective study of the diagnostic utility of N-terminal pro-brain natriuretic peptide (NTproBNP) measurements for predicting clinically significant patent ductus arteriosus (PDA) and assessing closure. METHODS: Plasma NTproBNP was measured during the first week in 100 preterm babies (mean gestation 28.8 +/- 2.9 weeks; mean birth weight 1224 +/- 512 g). Echocardiography was performed between days 5 and 7 by operators, blinded to NTproBNP concentration. RESULTS: NTproBNP peaked on days 2 and 3, declined by day 7. Twenty babies, later treated for PDA, had significantly higher NTproBNP levels throughout. Areas under receiver operating characteristic (ROC) curves were 0.896, 0.897 and 0.931 on days 2, 3 and 7, respectively (p < 0.0001). A concentration > 2850 pmol/L had diagnostic sensitivity of 90% and specificity of 89% (95% CI: 68, 99; likelihood ratio 8.10). Ductal closure was associated with a fall in mean NTproBNP from 3003 to 839 pmol/L (p < 0.001). CONCLUSION: N-terminal pro B-type brain natriuretic peptide (NTproBNP) concentrations peaked and then declined in the first week but remained higher in preterm babies whose PDA required treatment. NTproBNP on day 3 predicted whether a neonatal physician blinded to results would treat a PDA. Fall in plasma NTproBNP indicated closure.

Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model.

Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.

Isolation and characterization of the activated B-cell factor 1 homolog in Caenorhabditis elegans.

Members of the basic helix-loop-helix (bHLH) family of transcription factors regulate a wide array of developmental processes in many cell types, including cell fate specification, differentiation and morphogenesis. Our studies describe the cloning of a gene from the nematode Caenorhabditis elegans that is closely related to the vertebrate-activated B-cell factor (ABF) gene. The nematode gene product CeABF-1 was detected by northern blot analysis from RNA isolated from pooled nematodes representing different developmental stages. The developmental expression profile of CeABF-1 was shown by RT-PCR analysis to be predominantly expressed in the larval stages L3 and L4, with lower levels observed in the L2 larval stage and adult. We also show that CeABF-1 is capable of forming heterodimers with E2A proteins and binding E-box target sites. Mammalian cells transfected with CeABF-1 expression plasmids were capable of blocking E2A-mediated gene transcription, but full repression activity required the presence of two conserved amino acid residues found within the first helix of the CeABF-1 bHLH domain. These results suggest a conserved mechanism of gene repression between certain class II bHLH and class I bHLH proteins found in vertebrates and invertebrates.

Growth, bone maturation, and biochemical changes in Brazilian children from two different socioeconomic groups.

A study of blood biochemistry related to skeletal growth in 900 Brazilian children aged 7 to 17 yr is reported. Two groups were studied, a privileged and underprivileged sample. Anthropometry and measures of bone maturation in the control group were comparable with American and British standards. Underprivileged children showed growth impairment and delay in bone maturation. No signs of rickets were found in either group. Plasma calcium, magnesium, vitamin D, and total protein did not differ in the two groups of Brazilian children. Plasma alkaline phosphatase and inorganic phosphorus were abnormal in the underprivileged children. Alkaline-phosphatase activity and phosphorus levels did not fall towards adult levels after the predicted age of the adolescent spurt for underprivileged children. Menarche was delayed in the underprivileged girls.

Effect of nutrition on vitamin D status: studies on healthy and poorly nourished Brazilian children.

A cross-sectional study was carried out of 412 healthy and 226 chronically malnourished children in Recife, Brazil. Anthropometric measurements, x-rays of hands and wrists, and biochemical data related to skeletal growth were obtained. Levels of plasma 25 hydroxyvitamin D were measured in both groups of children and both showed higher concentrations than those reported for normal European children. The high levels of 25 hydroxyvitamin D found in these two groups of Brazilian children are probably the result of the intense solar radiation in this part of Brazil and argue against the diet being an important source of vitamin D in poorly nourished children. Some bone abnormalities were seen in the underprivileged group of children but in view of our findings these were more likely to be a result of protein-energy malnutrition than rickets.

Studies to confirm the source of 11 beta-hydroxyandrostenedione.

In a longitudinal study of 82 children we found a gradual rise in median plasma concentrations of 11 beta-hydroxyandrostenedione (11 beta-OH-A4) from 2.5 to 6.4 nmol/l during childhood which was similar in both sexes. This could reflect changes in adrenal function during the adrenarche and sexual maturation. Plasma concentrations of 11 beta-OH-A4 in adults follow the patterns of cortisol secretion. In patients with diseases of the adrenal cortex, the plasma concentrations of 11 beta-OH-A4 were consistent with the pathology of each condition. In women with polycystic ovaries (PCO) undergoing gonadotrophic stimulation for in vitro fertilization and embryo transfer, 11 beta-OH-A4 (median = 3.8 nmol/l), testosterone and androstenedione, were raised when compared to women with normal ovaries (11 beta-OH-A4 median = 2.6 nmol/l). Follicular fluid has concentrations of 11 beta-OH-A4 six to twelve times greater than plasma levels and in women with PCO, 11 beta-OH-A4 concentrations were lower than in women with normal ovaries, which is consistent with an inhibition of ovarian 11 beta-hydroxylase. Granulosa cells in vitro demonstrated the production of 11 beta-OH-A4 by side chain cleavage of cortisol. These data support an adrenal source for 11 beta-OH-A4 but the raised plasma concentrations in women with polycystic ovary syndrome (PCOS) may reflect the excess androgen output from the ovary. 11 beta-OH-A4 may therefore be an additional marker for ovarian dysfunction.

Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2.

The activated B-cell factor (ABF)-1 cDNA was initially isolated from Epstein-Barr virus (EBV)-infected B cells and codes for a DNA-binding protein belonging to the basic helix-loop-helix (bHLH) family of transcription factors. In this study, we characterized the nuclear localization signal of ABF-1, mapped two distinct transcriptional repression domains, and identified one ABF-1-interacting protein, Id-2. By examining the subcellular location of deletion mutants of ABF-1 fused to green fluorescent protein (GFP), critical regions involved in nuclear localization were determined. Analysis of GFP-tagged ABF-1 deletion mutants revealed two separate regions capable of directing nuclear localization. One region mapped to the N-terminal amino acids 71 to 103, whereas the second region localized to the C-terminal bHLH domain. Transient transfection of ABF-1 deletion mutants demonstrated that the N-terminal amino acids 1 to 40 and the bHLH domain function together to achieve maximum repression of E2A activity. Taken together, these results indicate that ABF-1 is a nuclear transcriptional repressor with two distinct regions that function in a synergistic fashion to attenuate E2A-mediated gene activation.

A flexible microprocessor system for the measurement of cell size.

A flexible system for the measurement of length and area is described. The system consists of the Reichert Jung MOP-1 area measuring device interfaced with a Commodore PET computer. Its use is illustrated by the planimetric measurement of cross sectional areas in histochemical preparations of normal and diseased muscle. While measurements are being made data can be displayed on the computer screen either in numerical form or as a frequency histogram together with simple statistical analyses. Hard copy can be obtained from an attached printer. Mean values for fibre area in normal human skeletal muscle are reported. An alternative, widely used method of calculating fibre area from the lesser diameter was found to give a consistent underestimate of approximately 30% when compared with our planimetric method. In diseased muscle with abnormally shaped fibres the discrepancy is even larger; such fibres can be identified using a "form factor" which relates the area of a cell to its perimeter. This rapid, accurate and flexible system is also suitable for the measurement of many different types of graphical record.

Muscle morphology and metabolism in hypothyroid myopathy: effects of treatment.

Needle biopsies from vastus lateralis in untreated hypothyroid patients with muscle weakness confirmed by quadriceps force measurements (n = 11) were repeated when the patients had taken L-thyroxine for a mean period of 9.2 months (range 5.3-13.3 months, n = 8) and had been continuously biochemically euthyroid for a mean period of 4.9 months (range 2-11 months). Biopsies were analysed biochemically for mitochondrial function. On light microscopy, histochemical examination, mean fibre areas and fibre percentages of type I and type II fibres were determined. Electronmicroscopy was also performed. Abnormalities on light microscopy occurred in eight patients of which type II fibre atrophy was the commonest and of the remainder two patients showed a myopathic electromyogram (EMG) and a raised plasma creatine kinase activity and one ultrastructural change on biopsy. After treatment resolution of pathological changes was often slow and half the patients had persistent abnormalities when rebiopsied. The type I mean fibre area was significantly increased in the eight hypothyroid females (p less than 0.05) and type II mean fibre areas tended to be low and in females this was significant (p less than 0.05). After treatment the type I mean fibre area was significantly reduced (p = 0.05). The type II mean fibre area also tended to fall but this was not significant (p greater than 0.05). No change in the fibre percentages occurred. A myopathic EMG, a raised plasma creatine kinase activity, ultrastructural changes and low mitochondrial enzyme activities on needle biopsy were other common findings and their significance is discussed.

Modeling developmental changes in strength and aerobic power in children.

The present study examined two contrasting multilevel model structures to describe the developmental (longitudinal) changes in strength and aerobic power in children: 1) an additive polynomial structure and 2) a multiplicative structure with allometric body size components. On the basis of the maximum log-likelihood criterion, the multiplicative "allometric" model was shown to be superior to the additive polynomial model when fitted to the data from two published longitudinal studies and to provide more plausible solutions within and beyond the range of observations. The multilevel regression analysis of study 1 confirmed that aerobic power develops approximately in proportion to body mass, m1/3. The analyses from study 2 identified a significant increase in quadriceps and biceps strength, in proportion to body size, plus an additional contribution from age, centered at about peak height velocity (PHV). The positive "age" term for boys suggested that at PHV the boys were becoming stronger in the quadriceps and biceps in relation to their body size. In contrast, the girls' age term was either negligible (quadriceps) or negative (biceps), indicating that at PHV the girls' strength was developing in proportion to or, in the case of the biceps, was becoming weaker in relation to their body size.

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

Cellular infiltrates in human skeletal muscle: exercise induced damage as a model for inflammatory muscle disease?

The type and distribution of mononuclear cell infiltrates in muscle biopsies taken from 9 subjects at differing times after exercise in which the muscle is stretched (eccentric exercise) has been characterised. The appearances are compared to those seen in muscle from patients with inflammatory muscle disease. After exercise infiltrating cells were seen in perivascular, perimysial and endomysial regions, the extent being greater in the later biopsies (9-14 days). The predominant cell type was the macrophage (46-100% of all infiltrating cells), the remainder were T lymphocytes with a predominance of the CD4 positive helper/inducer subset. Approximately one third of the T cells expressed DA2 (class 2) antigen indicating that they were activated. Very few B lymphocytes and no Leu7 positive cells were seen. There was evidence of class 1 expression on some of the damaged muscle fibres. The appearance of the experimentally damaged muscle in normal subjects was very similar to untreated polymyositis suggesting that a proportion of the infiltrating cells seen in this disease may be present as part of a natural response to damage rather than being its cause.