Accelerated resolution therapy and a thematic approach to military experiences in US Special Operations Veterans.

Accelerated Resolution Therapy (ART) is an emerging therapeutic intervention that has demonstrated effectiveness in treating post-traumatic stress, anxiety and depression. The ART protocol aligns with first-line trauma-focused psychotherapies and clinical guides in the USA and UK. This review addresses previous ART research that includes members of US Special Operations Forces. Observations from that research has led to a thematic conceptualisation of trauma through ART interventions. These include three clusters of traumatic memories and several themes relevant to individual distress but not necessarily symptoms that meet diagnostic criteria for PTSD. ART represents a movement in treatment away from the symptoms, to the individuals' story. Not only the story of an event, but how that experience becomes incorporated into one's sense of identity. The themes identified (and treated with ART) appear to have broader application to the entirety of one's military experience, not just PTSD. These themes may be helpful in directing treatment and may help to focus on significant aspects of service not traditionally associated with PTSD. Theoretically, some of these areas may have protective implications in suicide.

A biomarker panel predicts progression of Barrett's esophagus to esophageal adenocarcinoma.

Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.

Understanding the potential for selective natural organic matter removal by ion exchange.

Dissolved organic carbon (DOC) removal from a river water source was investigated using ion exchange (IEX), coagulation and membrane filtration. This research linked the variable charge characteristics of the organic compounds present in the source water with removal by IEX and coagulation. The raw water charge density fluctuated considerably (between 5.4 and 10.7 meq mgDOC-1) and controlled removal of the charge loading. Importantly, charge density was not correlated with the organic carbon concentration. The combined IEX and coagulation process reduced the specific DBP-FP (sDBP-FP) of the final water, with values as low as 18 µg mgDOC-1 for both haloacetic acids and trihalomethanes. IEX removed a particular fraction of NOM that 1) enhanced coagulation efficiency, providing increased removal of overall DOC; and 2) enabled coagulation to subsequently remove higher levels of specific components of NOM that have a high DBP-FP. The component of NOM removed by IEX that had a positive impact on coagulation was identified to be charged low molecular weight organic compounds of all hydrophobicity levels, resulting in a reduced specific DBP-FP compared to coagulation alone.

Is celecoxib a useful adjunct in the treatment of post-tonsillectomy pain in the adult population? A randomised, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of celecoxib for pain management in post-tonsillectomy adult patients. DESIGN: A randomised, double-blind, placebo-controlled, phase 3 clinical trial was conducted in an adult population (aged 18-55 years), with a parallel group design using an allocation ratio of 1:1. METHODS: Eighty patients underwent elective tonsillectomy or adenotonsillectomy, operated on by one surgeon. They were discharged home with randomly assigned celecoxib or placebo, together with regular post-tonsillectomy medications (paracetamol and Endone). Pain scores were measured from post-operative days 1 to 10. All patients were assessed on post-operative days 5, 12 and 28. RESULTS: There were no statistically significant differences in the daily or overall pain scores, the total intake of Endone, or the time taken to achieve freedom from pain after tonsillectomy between the study arms (n = 40 each arm). The celecoxib-treated group experienced significantly more vomiting (celecoxib vs placebo p < 0.001 (Mann-Whitney test), confidence interval = 0.57 to 0.76). CONCLUSION: Celecoxib usage was associated with significantly more vomiting and did not reduce narcotic analgesia requirement post-tonsillectomy.

Peri-operative management of the obese surgical patient 2015: Association of Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric Anaesthesia.

Guidelines are presented for the organisational and clinical peri-operative management of anaesthesia and surgery for patients who are obese, along with a summary of the problems that obesity may cause peri-operatively. The advice presented is based on previously published advice, clinical studies and expert opinion.

Mechanisms of action of therapeutic antibodies for cancer.

The therapeutic utility of antibodies and their derivatives is achieved by various means. The FDA has approved several targeted antibodies that disrupt signaling of various growth factor receptors for the treatment of a number of cancers. Rituximab, and other anti-CD20 monoclonal antibodies are active in B cell malignancies. As more experience has been gained with anti-CD20 monoclonal antibodies, the multifactorial nature of their anti-tumor mechanisms has emerged. Other targeted antibodies function to dampen inhibitory checkpoints. These checkpoint inhibitors have recently achieved dramatic results in several cancers, including melanoma. These and related antibodies continue to be investigated in the clinical and pre-clinical settings. Novel antibody structures that target two or more antigens have also made their way into clinical use. Tumor targeted antibodies can also be conjugated to chemo- or radiotherapeutic agents, or catalytic toxins, as a means to deliver toxic payloads to cancer cells. Here we provide a review of these mechanisms and a discussion of their relevance to current and future clinical applications.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model.

OBJECTIVE: This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS: Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS: A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS: The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

A practical workshop for generating simple DNA fingerprints of plants.

Gel electrophoresis DNA fingerprints offer a graphical and visually appealing illumination of the similarities and differences between DNA sequences of different species and individuals. A polymerase chain reaction (PCR) and restriction digest protocol was designed to give high-school students the opportunity to generate simple fingerprints of plants thereby illustrating concepts and techniques in genetics and molecular biology. Three combinations of primers/restriction enzyme targeting chloroplast DNA were sufficient to generate patterns that enabled visual discrimination of plant species. The protocol was tested with a range of common fruit, vegetable, and herb plants that could be easily cultivated and handled in the laboratory. Toxic or hazardous materials such as ethidium bromide and liquid nitrogen were avoided. The protocol was validated as a university outreach workshop targeted at a group of up to 10 high-school students. In a teaching laboratory, students sampled plants, setup the PCR reaction and restriction digest using microliter pipettes, and loaded the digested samples on an agarose gel. The workshop was structured as 2 × 2.5-hour sessions on separate days. The main challenges stemmed from the speed and accuracy of pipetting, especially at the gel loading stage. Feedback from students was largely positive, with the majority reporting that they had both enjoyed and learnt from the experience.

Strychnine poisoning: gone but not forgotten.

Strychnine was used as a pesticide until 1968 and a rodenticide until 2006 when its sale was banned throughout the EU and all supplies recalled. A case of strychnine poisoning seen in a UK emergency department in 2009 is reported to remind clinicians of the features and management of this increasingly rare presentation. Prompt recognition and early intensive supportive therapy can result in a favourable outcome.

Impaired functional capacity is associated with all-cause mortality after major elective intra-abdominal surgery.

BACKGROUND: Studies of preoperative cardiopulmonary exercise testing (CPET) have shown that a reduced oxygen uptake at anaerobic threshold (AT) and elevated ventilatory equivalent for carbon dioxide (VE/VCO(2)) were associated with reduced short- and medium-term survival after major surgery. The aim of this study was to determine the relative values of these, and also clinical risk factors, in identifying patients at risk of death after major intra-abdominal, non-vascular surgery. METHODS: Patients aged >55 yr, undergoing elective colorectal resection, radical nephrectomy, or cystectomy between June 2004 and May 2009 had CPET during their routine pre-assessment clinic visit. We performed a retrospective analysis of known clinical risk factors and data from CPET to assess their relationship to all-cause mortality after surgery. RESULTS: Eight hundred and forty-seven patients underwent surgery, of whom 18 (2.1%) died. A clinical history of ischaemic heart disease (RR 3.1, 95% CI 1.3-7.7), a VE/VCO(2) >34 (RR 4.6, 95% CI 1.4-14.8), and an AT < or =10.9 ml kg(-1) min(-1) (RR 6.8, 95% CI 1.6-29.5) were all significant predictors of all-cause hospital and 90 day mortality. The effect of reduced AT was most pronounced in patients with no history of cardiac risk factors (RR 10.0, 95% CI 1.7-61.0). CONCLUSIONS: The routine measurement of AT and VE/VCO(2) using CPET for patients undergoing high-risk surgery can accurately identify the majority of high-risk patients, while the use of clinical risk factors alone will only identify a relatively small proportion of at-risk patients.

Sleep disturbance and melatonin levels following traumatic brain injury.

OBJECTIVES: Sleep disturbances commonly follow traumatic brain injury (TBI) and contribute to ongoing disability. However, there are no conclusive findings regarding specific changes to sleep quality and sleep architecture measured using polysomnography. Possible causes of the sleep disturbances include disruption of circadian regulation of sleep-wakefulness, psychological distress, and a neuronal response to injury. We investigated sleep-wake disturbances and their underlying mechanisms in a TBI patient sample. METHODS: This was an observational study comparing 23 patients with TBI (429.7 +/- 287.6 days post injury) and 23 age- and gender-matched healthy volunteers on polysomnographic sleep measures, salivary dim light melatonin onset (DLMO) time, and self-reported sleep quality, anxiety, and depression. RESULTS: Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls. Patients with TBI showed decreased sleep efficiency (SE) and increased wake after sleep onset (WASO). Although no significant group differences were found in sleep architecture, when anxiety and depression scores were controlled, patients with TBI showed higher amount of slow wave sleep. No differences in self-reported sleep timing or salivary DLMO time were found. However, patients with TBI showed significantly lower levels of evening melatonin production. Melatonin level was significantly correlated with REM sleep but not SE or WASO. CONCLUSIONS: Reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis. The results suggest that there are at least 2 factors contributing to sleep disturbances in patients with traumatic brain injury. We propose that elevated depression is associated with reduced sleep quality, and increased slow wave sleep is attributed to the effects of mechanical brain damage.

Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety symptoms are associated with polydrug, not ecstasy, use.

Although previous studies have examined anxiety and depression in ecstasy (+/-3,4-methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms are associated specifically with ecstasy or with polydrug use in general. We compared mean symptomatology and clinically significant symptoms in 45 ecstasy polydrug, 48 cannabis polydrug and 40 legal drug users, who completed standardised self-report anxiety and depression symptom measures. We further examined whether group differences were secondary to increased somatic symptom reporting, which may reflect acute/subacute drug effects. Anxiety and depression scores were higher in polydrug than legal drug users, with no difference between ecstasy and cannabis groups. There was no difference in numbers meeting criteria for clinically significant depression or 'moderate' or 'severe' anxiety, but the polydrug group contained more individuals reporting at least 'mild' anxiety symptoms than the legal drug control. Multivariate analyses indicated that anxiety alone was sufficient to discriminate groups. Polydrug users reported more somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy polydrug users may be associated with polydrug rather than ecstasy use. Higher ratings in polydrug users appear to be secondary to increased somatic symptom reporting, suggesting possible impacts of drug effects on symptom endorsement.

Neuroendocrine and subjective responses to pharmacological challenge with citalopram: a controlled study in male and female ecstasy/MDMA users.

Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') causes persistent alterations to the serotonergic system of animals, evidence for long-term neurological effects of ecstasy/MDMA in humans remains equivocal. The current study assessed serotonin functioning of nine male and 11 female recreational ecstasy polydrug users by measuring neuroendocrine (prolactin, cortisol) responses to pharmacological challenge with the selective serotonin reuptake inhibitor citalopram, compared with nine male and five female cannabis polydrug users and 11 male and 11 female non-drug using controls. A single-blind, randomised, placebo-controlled design was used. Subjective responses, other substance use, mood, personality traits and demographic variables were measured to control for potentially confounding variables. There were no significant differences between ecstasy polydrug users, cannabis polydrug users and non-drug using controls in neuroendocrine or subjective responses to serotonergic challenge, and there were no sex by drug group interactions. There was no relationship between extent of ecstasy use and neuroendocrine functioning, alone or in combination with potential confounding variables. Subjective responses to the pharmacological challenge (nausea, tremor, dry mouth), novelty seeking and lifetime dose of alcohol were the only variables that contributed to one or more of the neuroendocrine outcome variables. These data do not support the premise that recreational ecstasy/MDMA use results in measurable impairment of serotonergic control of endocrine activity.

Metamemory in recreational ecstasy polydrug users: what do self-reports of memory failures mean?

Previous research has found relationships between self-rated memory and ecstasy use, such that heavier users report worse function. These findings have been interpreted in terms of objective memory capacity. However, research on metamemory suggests that self-reported memory may be only weakly related to objective function, with demographics, mood, and memory-related beliefs and feelings also contributing to ratings. This study examined relationships between ecstasy/other drug use and self-reported memory, controlling for effects of demographic factors and mood. Associations between self-reported memory, memory-related beliefs and feelings, and objectively-measured cognitive function were also examined. Forty-five ecstasy polydrug, 48 cannabis polydrug, and 40 legal drug users completed a battery of neuropsychological tests and questionnaire measures of metamemory, including memory-related control beliefs, memory-related anxiety, and self-reported prospective and general/retrospective memory. The combined polydrug groups reported more general/retrospective memory failures. Covariance analysis, however, suggested that this finding was confounded by general anxiety levels. A combination of objective cognitive measures contributed to prediction of self-rated prospective memory, with demographics, mood, and memory-related anxiety also contributing to variability. However, associations between objective and self-reported memory were not strong. Self-report may not be a specific methodology with which to assess objective memory capacities in ecstasy and other drug users.

Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds.

BACKGROUND: Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds. METHOD: A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed. RESULTS: It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1-6% of variance in cognitive scores. CONCLUSIONS: Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients.

BACKGROUND: The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7-9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection. METHODS: An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected. RESULTS: Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant Staphylococcus aureus (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p<0.001), an increased C reactive protein level (p<0.05), and a longer stay in the intensive care unit (p<0.01). Length of stay did not determine which patients acquired MRSA. CONCLUSION: The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.

The effect of traumatic brain injury on the timing of sleep.

While there have been single case reports of the development of circadian rhythm sleep disorders, most commonly delayed sleep phase syndrome following traumatic brain injury (TBI), to our knowledge there have been no group investigations of changes to sleep timing in this population. The aim of the present study was to investigate sleep timing following TBI using the dim light melatonin onset (DLMO) as a marker of circadian phase and the Morningness-Eveningness Questionnaire (MEQ) as a measure of sleep-wake behavior. A sleep-wake diary was also completed. It was hypothesized that the timing of DLMO would be delayed and that there would be a greater tendency toward eveningness on the MEQ in a post-acute TBI group (n=10) compared to a gender and age matched control group. Participants were recruited at routine outpatient review appointments (TBI) and from the general population (control) as part of a larger study. They attended the sleep laboratory where questionnaires were completed, some retrospectively, and saliva melatonin samples were collected half-hourly according to a standard protocol. The results show that the TBI and control groups reported similar habitual sleep times and this was reflected on the MEQ. There was, however, significant variability in the TBI group's change from the pre-injury to the current MEQ score. The timing of melatonin onset was not different between the groups. While subtle changes (advances or delays) in this small sample may have cancelled each other out,. the present study does not provide conclusive objective evidence of shift in circadian timing of sleep following TBI. Furthermore, although participants did report sleep timing changes, it is concluded that the MEQ may not be suitable for use with this cognitively impaired clinical group.

Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss. METHODS: We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC). RESULTS: There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group. CONCLUSIONS: In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.

Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study.

PURPOSE: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. METHODS: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. RESULTS: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). CONCLUSIONS: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.

Air distribution in the Borden aquifer during in situ air sparging.

A field experiment was conducted at Canadian Forces Base Borden (CFB Borden) to assess the air distribution from a single in situ air sparging injection point. This aquifer consists of fine to medium sand deposited in horizontal layers. The permeability at the study location varied from 10(-10) to 10(-14) m2 and distinct low permeability horizons were present at approximately 1.2, 2.0, and 2.9 m below the water table. Prior to air injection, a 15x15-m portion of the vadose zone was excavated to the water table (approximately 1 m below ground surface) in order to visually observe air release distribution at the water table. The water table was actively maintained 5 cm above the excavated surface. The sparging system operated for a period of 7 days with an injection flow rate of 200 m3/days (5 scfm). The resulting subsurface air distribution was assessed using a variety of techniques including neutron logging, borehole and surface ground penetrating radar, piezometric head measurements, surface visualization, and hydraulic testing. Through this combination of tests, it was demonstrated that variations in permeability and, hence, capillary pressure at the site were sufficient to cause the injected air to spread laterally, forming stratigraphically trapped air pockets beneath the low permeability horizons. The formation of these air pockets eventually resulted in a buildup of capillary pressure that exceeded the air entry pressure and allowed some air to migrate up through the lower permeability layers. Each of the assessment techniques employed generated information at different spatial scales that prevented a direct comparison of the results from the various techniques; however, the results from all techniques proved to be critical in the interpretation of the experimental data. As a consequence, the different assessment techniques should not be viewed as alternatives, but rather as complimentary techniques.