Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: A regional burns centre experience.

INTRODUCTION: Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially fatal desquamative disorders characterised by large areas of partial thickness skin and mucosal loss. The degree of epidermal detachment that occurs has led to SJS/TEN being described as a burn-like condition. These patients benefit from judicious critical care, early debridement and meticulous wound care. This is best undertaken within a multidisciplinary setting led by clinicians experienced in the management of massive skin loss and its sequelae. In this study, we examined the clinical outcomes of SJS/TEN overlap & TEN patients managed by our regional burns service over a 12-year period. We present our treatment model for other burn centres treating SJS/TEN patients. METHODS: A retrospective case review was performed for all patients with a clinical diagnosis of TEN or SJS/TEN overlap admitted to our paediatric and adult burns centre between June 2004 and December 2016. Patient demographics, percentage total body surface area (%TBSA), mucosal involvement, causation, severity of illness score (SCORTEN), length of stay and survival were appraised with appropriate statistical analysis performed using Graph Pad Prism 7.02 Software. RESULTS: During the study period, 42 patients (M26; F: 16) with TEN (n=32) and SJS/TEN overlap (n=10) were managed within our burns service. Mean %TBSA of cutaneous involvement was 57% (range 10-100%) and mean length of stay (LOS) was 27 days (range 1-144 days). We observed 4 deaths in our series compared to 16 predicted by SCORTEN giving a standardised mortality ratio (SMR) of 24%. CONCLUSION: Management in our burns service with an aggressive wound care protocol involving debridement of blistered epidermis and wound closure with synthetic and biological dressings seems to have produced benefits in mortality when compared to predicted outcomes.

Development of a core outcome set for research and audit studies in reconstructive breast surgery.

BACKGROUND: Appropriate outcome selection is essential if research is to guide decision-making and inform policy. Systematic reviews of the clinical, cosmetic and patient-reported outcomes of reconstructive breast surgery, however, have demonstrated marked heterogeneity, and results from individual studies cannot be compared or combined. Use of a core outcome set may improve the situation. The BRAVO study developed a core outcome set for reconstructive breast surgery. METHODS: A long list of outcomes identified from systematic reviews and stakeholder interviews was used to inform a questionnaire survey. Key stakeholders defined as individuals involved in decision-making for reconstructive breast surgery, including patients, breast and plastic surgeons, specialist nurses and psychologists, were sampled purposively and sent the questionnaire (round 1). This asked them to rate the importance of each outcome on a 9-point Likert scale from 1 (not important) to 9 (extremely important). The proportion of respondents rating each item as very important (score 7-9) was calculated. This was fed back to participants in a second questionnaire (round 2). Respondents were asked to reprioritize outcomes based on the feedback received. Items considered very important after round 2 were discussed at consensus meetings, where the core outcome set was agreed. RESULTS: A total of 148 items were combined into 34 domains within six categories. Some 303 participants (51·4 per cent) (215 (49·5 per cent) of 434 patients; 88 (56·4 per cent) of 156 professionals) completed and returned the round 1 questionnaire, and 259 (85·5 per cent) reprioritized outcomes in round 2. Fifteen items were excluded based on questionnaire scores and 19 were carried forward to the consensus meetings, where a core outcome set containing 11 key outcomes was agreed. CONCLUSION: The BRAVO study has used robust consensus methodology to develop a core outcome set for reconstructive breast surgery. Widespread adoption by the reconstructive community will improve the quality of outcome assessment in effectiveness studies. Future work will evaluate how these key outcomes should best be measured.

The relationship between eosinophilia and airway remodelling in mild asthma.

BACKGROUND: Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. OBJECTIVE: The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. METHODS: Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0-0.45 mm(-2)) ) or high submucosal eosinophil (23.43-46.28 mm(-2) ) counts and healthy controls were assessed for in vivo epithelial damage (using epidermal growth factor receptor staining), mucin expression, airway smooth muscle (ASM) hypertrophy and inflammatory cells within ASM. RESULTS: The proportion of in vivo damaged epithelium was significantly greater (P = 0.02) in the high-eosinophil (27.37%) than the low-eosinophil (4.14%) group. Mucin expression and goblet cell numbers were similar in the two eosinophil groups; however, MUC-2 expression was increased (P = 0.002) in the high-eosinophil group compared with controls. The proportion of submucosa occupied by ASM was higher in both asthma groups (P = 0.021 and P = 0.046) compared with controls. In the ASM, eosinophil and T-lymphocyte numbers were higher (P < 0.05) in the high-eosinophil group than both the low-eosinophil group and the controls, whereas the numbers of mast cells were increased in the high-eosinophil group (P = 0.01) compared with controls. CONCLUSION: Submucosal eosinophilia is a marker (and possibly a cause) of epithelial damage and is related to infiltration of ASM with eosinophils and T lymphocytes, but is unrelated to mucus metaplasia or smooth muscle hypertrophy.

A simple model for multicomponent etching.

We consider the situation where a multicomponent solid is etched using one or more acids. Of fundamental interest is the rate of surface etching but when this involves multicomponent surface reactions, it becomes unclear how the overall rate can be estimated. In this paper, we sketch a simple model designed to determine the effective etching rate by means of an atomic scale model of the etching process.

Development and validation of a clinical index to predict survival after cardiac resynchronisation therapy.

OBJECTIVE: To develop and validate a prognostic risk index of cardiovascular mortality after cardiac resynchronisation therapy (CRT). DESIGN: Prospective cohort study. SETTING: District general hospital. PATIENTS: 148 patients with heart failure (mean age 66.7 (SD 10.4) years), New York Heart Association class III or IV, LVEF <35%) who underwent CRT. INTERVENTIONS: CRT device implantation. MAIN OUTCOME MEASURES: Value of a composite index in predicting cardiovascular mortality, validated internally by bootstrapping. The predictive value of the index was compared to factors that are known to predict mortality in patients with heart failure. RESULTS: All patients underwent assessment of 16 prognostic risk factors, including cardiovascular magnetic resonance (CMR) measures of myocardial scarring (gadolinium-hyperenhancement) and dyssynchrony, before implantation. Clinical events were assessed after a median follow-up of 913 (interquartile range 967) days. At follow-up, 37/148 (25%) of patients died from cardiovascular causes. In Cox proportional hazards analyses, (DSC) Dyssynchrony, posterolateral Scar location (both p<0.0001) and Creatinine (p = 0.0046) emerged as independent predictors of cardiovascular mortality. The DSC index, derived from these variables combined, emerged as a powerful predictor of cardiovascular mortality. Compared to patients with a DSC <3, cardiovascular mortality in patients in the intermediate DSC index (3-5; HR: 11.1 (95% confidence interval (CI) 3.00 to 41.1), p = 0.0003) and high DSC index (> or =5; HR: 30.5 (95% CI 9.15 to 101.8), p<0.0001) were higher. Bootstrap validation confirmed excellent calibration and internal validity of the prediction model. CONCLUSION: The DSC index, derived from a standard CMR scan and plasma creatinine before implantation, is a powerful predictor of cardiovascular mortality after CRT.

Influence of constant positive airway pressure therapy on lipid storage, muscle metabolism and insulin action in obese patients with severe obstructive sleep apnoea syndrome.

AIM: To observe the effect of constant positive airway pressure (CPAP) therapy on regional lipid deposition, muscle metabolism and glucose homeostasis in obese patients with obstructive sleep apnoea syndrome (OSAS). METHODS: A total of 29 obese patients underwent assessment before and after a minimum of 12-week CPAP therapy. Abdominal adipose tissue was assessed using magnetic resonance imaging. Intramyocellular lipid (IMCL) and skeletal muscle creatine were assessed using (1)H-magnetic resonance spectroscopy. Fasting venous and arterial blood were collected. Glucose control was assessed using the homeostatic model. A subgroup of six patients were also evaluated for skeletal muscle pH, phosphocreatine (PCr) and mitochondrial function using (31)P-magnetic resonance spectroscopy. The sample was divided according to CPAP therapy, with regular users defined as a minimum nightly use of >or=4 h; 19 subjects were regular and 10 were irregular CPAP users. RESULTS: Visceral adipose tissue volume and circulating leptin were reduced with regular CPAP use but not with irregular CPAP use. Regular CPAP use also produced an increase in skeletal muscle creatine and resting PCr and a decrease in muscle pH. Neither the regular nor irregular CPAP users showed any change in IMCL content, insulin sensitivity scores or mitochondrial function. CONCLUSIONS: These data show that regular CPAP therapy reduces visceral adipose tissue and leptin and improves skeletal muscle metabolites. In obese patients with severe OSAS, regular CPAP use does not improve glucose control, suggesting that the influence of obesity on glucose control dominates over any potential effect of OSAS.

Suturing of lacerations of skeletal muscle.

Our aim was to compare the biomechanical properties of suturing methods to determine a better method for the repair of lacerated skeletal muscle. We tested Kessler stitches and the combination of Mason-Allen and perimeter stitches. Individual stitches were placed in the muscle belly of quadriceps femoris from a pig cadaver and were tensioned mechanically. The maximum loads and strains were measured and failure modes recorded. The mean load and strain for the Kessler stitches were significantly less than those for combination stitches. All five Kessler stitches tore out longitudinally from the muscle. All five combination stitches did not fail but successfully elongated. Our study has shown that the better method of repair for suturing muscle is the use of combination stitches.

Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD.

BACKGROUND: Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease (COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria. METHODS: Sixty five subjects (11 healthy smokers, 44 smokers with stage 0-IV COPD, and 10 healthy non-smokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation. RESULTS: Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction (r = -0.64, p<0.001) than did inspiratory HRCT measurements (which reflect emphysema severity; r = -0.45, p<0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction (r = 0.55, p<0.001) but did not correlate with HRCT indicators of the severity of emphysema. CONCLUSIONS: This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.

Poly(sodium 4-styrene sulfonate): evaluation of a topical microbicide gel against herpes simplex virus type 2 and Chlamydia trachomatis infections in mice.

OBJECTIVE: To investigate the in vivo activity of poly(sodium 4-styrene sulfonate) (T-PSS) gel formulations as topical microbicides. METHODS: The ability of the gel formulations to reduce the incidence of infection when applied prior to pathogen challenge was examined in mouse models of vaginal herpes simplex type 2 (HSV-2) and Chlamydia trachomatis infection, and rectal HSV-2 infection. RESULTS: In the vaginal HSV-2 challenge studies, 10% T-PSS gel provided significant protection against infection, even when administered 60 min prior to virus challenge (P < 0.0001). Both 5% and 10% T-PSS gel formulations significantly reduced the incidence of upper genital tract C. trachomatis infection in animals treated up to 5 min before challenge (P < 0.001). However, no protection against C. trachomatis infection was seen in animals treated 30 min before challenge. In mice challenged rectally with HSV-2, both the 5% and 10% T-PSS gels significantly reduced infection at 20 s (P < 0.01 for both). However, only the 10% gel provided significant protection when administered 5 min before challenge (P < 0.01). CONCLUSIONS: T-PSS gel formulations have promising in vivo activity as topical microbicides.

Abiogenic formation of alkanes in the Earth's crust as a minor source for global hydrocarbon reservoirs.

Natural hydrocarbons are largely formed by the thermal decomposition of organic matter (thermogenesis) or by microbial processes (bacteriogenesis). But the discovery of methane at an East Pacific Rise hydrothermal vent and in other crustal fluids supports the occurrence of an abiogenic source of hydrocarbons. These abiogenic hydrocarbons are generally formed by the reduction of carbon dioxide, a process which is thought to occur during magma cooling and-more commonly-in hydrothermal systems during water-rock interactions, for example involving Fischer-Tropsch reactions and the serpentinization of ultramafic rocks. Suggestions that abiogenic hydrocarbons make a significant contribution to economic hydrocarbon reservoirs have been difficult to resolve, in part owing to uncertainty in the carbon isotopic signatures for abiogenic versus thermogenic hydrocarbons. Here, using carbon and hydrogen isotope analyses of abiogenic methane and higher hydrocarbons in crystalline rocks of the Canadian shield, we show a clear distinction between abiogenic and thermogenic hydrocarbons. The progressive isotopic trends for the series of C1-C4 alkanes indicate that hydrocarbon formation occurs by way of polymerization of methane precursors. Given that these trends are not observed in the isotopic signatures of economic gas reservoirs, we can now rule out the presence of a globally significant abiogenic source of hydrocarbons.

Herpes B-virus specific-pathogen-free breeding colonies of macaques (Macaca mulatta): diagnostic testing before and after elimination of the infection.

BACKGROUND AND PURPOSE: The National Institutes of Health's (NIH) National Center for Research Resources' (NCRR) Division of Comparative Medicine has funded the establishment of specific pathogen-free (SPF) captive macaque colonies. Herpes B-virus (Herpesvirus simiae, Cercopithecine herpesvirus type 1) has been targeted for elimination. Late seroconversion presents the greatest threat to the integrity of SPF colonies. The purpose of the study reported here was to evaluate that threat through detailed investigation of the patterns of seroreactivity and housing histories in one colony. METHODS: From 1990 through 1997, the B-virus Resource Laboratory screened macaques for B-virus, using ELISA or western immunoblot analysis. In 1993, we combined test results and housing histories to verify the seronegative status of one colony. RESULTS: Two groups of latently infected macaques were identified as to time and place of transmission. The infection was eradicated within 3 years (1990-1992), as judged by the absence of true positive seroreactivity in any screened macaques. New infections were not identified in four years of follow-up evaluation. CONCLUSION: With rigorous surveillance, the SPF status of the colony was achieved and maintained.

A survey of smoking cessation knowledge, training, and practice among U.S. Army general medical officers.

BACKGROUND: Historically, cigarette-smoking rates have been higher among military personnel than among civilians, although recently these rates have decreased. METHODS: In March 1997, a questionnaire assessing (1) training received on smoking cessation, (2) objective knowledge of smoking-cessation techniques, (3) frequency of practice habits, and (4) personal tobacco use among physicians, was successfully mailed to 232 of the total population of 279 Army general medical officers (GMOs). RESULTS: One-hundred-fifty (65%) GMOs returned questionnaires. Of these, 3.3% reported personal cigarette smoking, and 7.3% regularly used smokeless tobacco. During internship, few (13%) GMOs received smoking-cessation training. Primary care programs provided training more frequently than did surgery internship programs. The mean score on the objective knowledge portion was 72%. GMOs had a variable practice pattern in their use of smoking-cessation techniques (percent answering "usually" or "always"): helping patients set quit dates (35%), offering to prescribe the nicotine patch (59%), referring patients to a behavior-modification program (86%). Physicians who received training during internship were significantly more likely (p < 0.01) to help their patients set a quit date. Training did not result in a statistically increased frequency of other practice habits. CONCLUSIONS: GMOs received minimal training on smoking cessation during internship. GMOs refer patients to smoking-cessation classes, reflecting the strategy of the Army Health Promotion program. Strategies to increase the frequency that GMOs prescribe nicotine replacement and assist patients in setting a quit date are needed. Military smoking-cessation efforts may provide valuable lessons for the civilian community.

B-virus specific-pathogen-free breeding colonies of macaques (Macaca mulatta): retrospective study of seven years of testing.

BACKGROUND AND PURPOSE: National Institutes of Health's Division of Comparative Medicine has sponsored a multi-institutional program for the establishment of specific-pathogen-free (SPF) macaque colonies. B virus (Herpesvirus simiae, Cercopithecine herpesvirus type 1) has been targeted in this surveillance. Participating institutions have established individual timetables for frequency of testing and types of monitoring and husbandry techniques, all with the common goal of producing pathogen-free monkeys for research. The greatest biosecurity threat to the program comes from failure to detect seronegative latent infections, either in first-year macaques or macaques introduced in subsequent years, although these are supposed to operate as closed colonies. METHODS: From January 1990 through December 1996, we screened macaques for B virus, using enzyme-linked immunoabsorbant assay (ELISA) and Western blot analysis. RESULTS: During the first year, 1,097 macaques from six colonies were tested, and 88.4% tested negative for B virus. During the seventh year, 1,843 were tested, of which 99.7% tested negative. Seropositive macaques were detected as late as the seventh year. CONCLUSIONS: An aggressive program to establish an SPF colony of captive breeding macaques can be effective in reducing the risk of B-virus exposure.

Biphasic changes in left ventricular function during hyperdynamic endotoxemia.

Cardiac contractility was studied in a clinically relevant conscious swine model simulating human hemodynamics during endotoxemia. The slope of the end-systolic pressure-volume relationship [end-systolic elastance (EES)] was used as a load-independent contractility index. Chronic instrumentation in 10 pigs included two pairs of endocardial ultrasonic crystals for measuring internal major and minor axial dimensions of the left ventricle, a micromanometer for left ventricular pressure measurement, and a thermodilution pulmonary artery catheter. After a 10-day recovery period, control measurements of cardiac hemodynamic function were obtained. The following week, Escherichia coli endotoxin (10 micrograms . kg-1. h-1) was administered intravenously for 24 h. EES increased 1 h after endotoxin infusion and decreased beyond 7 h. The later hemodynamic changes resembled human cardiovascular performance during endotoxemia more closely than the changes during the acute phase. EES decreased in the later phase. A similar biphasic response of EES has been reported during a tumor necrosis factor-alpha (TNF) challenge. Even though plasma TNF was highest at 1 h and declined thereafter in this study, no consistent relationship between TNF and EES was identified, and TNF levels did not correlate directly with the changes in EES.

Effects of long-term hemofiltration on circulating mediators and superoxide production during continuous endotoxin administration.

BACKGROUND: The purpose of this study was to test whether continuous hemofiltration eliminates cytokines and eicosanoids, or stimulates granulocyte function. METHODS: Nineteen pigs were divided into a control group (n = 7), a hemofiltration group (n = 7), and an extracorporeal circuit only group (n = 5). All animals received the same amount of intravenous endotoxin and resuscitation fluid. Zero-balanced hemofiltration was started 30 minutes after initiation of endotoxemia and continued throughout the experiment. Plasma endotoxin, tumor necrosis factor-alpha, eicosanoids, superoxide production, and other physiologic parameters were measured before challenge and at scheduled intervals thereafter. RESULTS: Eicosanoids were filtered but plasma concentrations were not reduced. Tumor necrosis factor-alpha was not filtered or adsorbed. There were no significant differences between groups in any measured parameters. CONCLUSION: Continuous hemofiltration could not efficiently remove tumor necrosis factor-alpha or eicosanoids. Also, continuous hemofiltration did not stimulate production of the proinflammatory mediators measured, nor improve respiratory distress.

Hospital in the home: a randomised controlled trial.

OBJECTIVES: To compare treatment of acute illness at home and in hospital, assessing safety, effect on geriatric complications, and patient/carer satisfaction. DESIGN: Randomised controlled trial. SETTING: A tertiary referral hospital affiliated with the University of New South Wales. PARTICIPANTS: 100 patients (69% older than 65 years) with a variety of acute conditions, who were assessed in the emergency department as requiring admission to hospital. INTERVENTIONS: Patients were allocated at random to be treated by a hospital-in-the-home (HIH) service in their usual residence or to be admitted to hospital. MAIN OUTCOME MEASURES: Geriatric complications (confusion, falls, urinary incontinence or retention, faecal incontinence or constipation, phlebitis and pressure areas), patient/carer satisfaction, adverse events, and death. RESULTS: There was a lower incidence of confusion (0 v. 20.4% [95% CI, 9.1%-31.7%]; P = 0.0005), urinary complications (incontinence or retention) (2.0% [95% CI, -1.8%, 5.8%] v. 16.3% [95% CI, 6.0%, 26.6%]; P = 0.01), and bowel complications (incontinence or constipation) (0 v. 22.5% [95% CI, 10.7%, 34.1%]; P = 0.0003) among HIH-treated patients. No significant difference in number of adverse events and deaths (to 28 days after discharge) in the two groups was found (although numbers were small). Patient and carer satisfaction was significantly higher in the HIH group. CONCLUSIONS: Home treatment appears to provide a safe alternative to hospitalisation for selected patients, and may be preferable for some older patients. We found high levels of both patient and carer satisfaction with home treatment.

Inhaled nitric oxide prevents left ventricular impairment during endotoxemia.

We evaluated the effect of long-term inhalation of nitric oxide (NO) on cardiac contractility after endotoxemia by using the end-systolic elastance of the left ventricle (LV) as a load-independent contractility index. Chronic instrumentation in 12 pigs included implantation of two pairs of endocardial dimension transducers to measure LV volume and a micromanometer to measure LV pressure. One week later, the animals were divided into a control group (n = 6) or a NO group (n = 6). All animals received intravenous Escherichia coli endotoxin (10 micrograms. kg-1. h-1) and equivalent lactated Ringer solution. NO inhalation (20 parts/million) was begun 30 min after the initiation of endotoxemia and was continued for 24 h. In both groups, tachycardia, pulmonary hypertension, and systemic hyperdynamic changes were noted. The end-systolic elastance in the control group was significantly decreased beyond 7 h. NO inhalation maintained the end-systolic elastance at baseline levels and prevented its impairment. These findings indicate that NO exerts a protective effect on LV contractility in this model of endotoxemia.