Paediatric procedural sedation using ketamine in a UK emergency department: a 7 year review of practice.

BACKGROUND: Ketamine is growing in popularity for procedural sedation in the paediatric population, yet safety concerns remain. We performed a retrospective review of practice and outcomes of paediatric ketamine sedation using the World SIVA International Sedation Task Force reporting tool. METHODS: A retrospective inspection of the dedicated emergency department electronic sedation database and subsequent note and sedation chart review was performed for all paediatric sedations throughout a 7 yr period from September 2006. All adverse events were stratified. RESULTS: During the study period, procedural sedation was provided for a total of 243 children, of whom 215 were sedated with ketamine, most commonly for wound management (n=131). The median patient age was 4 yr (14 months to 15 yr), and 63.7% were male. Of the total, 76.7% were discharged home either directly (n=101) or after brief observation (n=64). One patient required subsequent general anaesthesia after a failed sedation with paradoxical agitation. Of the total, 9.8% of patients had an adverse event, the most severe risk stratification being 'minor risk'. All interventions were 'minimal risk'. There were no 'sentinel risk' outcomes. CONCLUSIONS: These data support the ongoing use of ketamine for paediatric procedural sedation in the emergency department by emergency physicians. Relatively high resource requirements mean that ensuring adequate numbers of procedures may prove challenging.

An exploration of the cognitive and affective processes for anaesthetists when performing an emergency front of neck airway.

Emergency front of neck airway (eFONA) is a potentially lifesaving but very high-stress procedure. We explored the cognitive and affective processes involved via semi-structured interviews with 17 UK anaesthetists who had attempted eFONA within the previous two years. Thematic analyses generated two meta-themes: 'Making the decision is the hardest part; the doing is easier' and 'What helps make the decision?'. We found concerns around scrutiny, lack of a flat hierarchy, unfamiliarity with the situation and the lack of a model for transitioning to eFONA. Culture change, using a shared mental model, priming and emotional disengagement, assisted with eFONA decision-making. Conclusions and implications for practice are presented.

Toll-like receptor-associated sequence variants and prostate cancer risk among men of African descent.

Recent advances demonstrate a relationship between chronic/recurrent inflammation and prostate cancer (PCA). Among inflammatory regulators, toll-like receptors (TLRs) have a critical role in innate immune responses. However, it remains unclear whether variant TLR genes influence PCA risk among men of African descent. Therefore, we evaluated the impact of 32 TLR-associated single-nucleotide polymorphisms (SNPs) on PCA risk among African Americans and Jamaicans. SNP profiles of 814 subjects were evaluated using Illumina's Veracode genotyping platform. Single and combined effects of SNPs in relation to PCA risk were assessed using age-adjusted logistic regression and entropy-based multifactor dimensionality reduction (MDR) models. Seven sequence variants detected in TLR6, TOLLIP (Toll-interacting protein), IRAK4 (interleukin-1 receptor-associated kinase 4) and IRF3 (interferon regulatory factor 3) were marginally related to PCA. However, none of these effects remained significant after adjusting for multiple hypothesis testing. Nevertheless, MDR modeling revealed a complex interaction between IRAK4 rs4251545 and TLR2 rs1898830 as a significant predictor of PCA risk among US men (permutation testing P-value=0.001). However, these findings require further assessment and validation.

Synchronous diagnosis of colorectal malignancy and lymphoma.

AIM: To perform case series from one centre over 9 years, and review of the literature. The synchronous diagnosis of colorectal malignancy and lymphoma is rare. METHOD: Case note review of patients identified from clinical databases. RESULTS: Five patients were identified and findings discussed. In two patients colorectal malignancy staging CT scans identified pathological lymphadenopathy consistent with lymphoma. A further two patients had an incidental lymphoma on histological examination of the colorectal malignancy specimen. The fifth patient was found to have suspicious superior mesenteric lymph nodes at laparotomy. Histology confirmed two nodular lymphocyte-predominant Hodgkin's lymphomas, a lymphocytic-rich classical Hodgkin's lymphoma, a diffuse large B-cell lymphoma and a B-cell follicular lymphoma. CONCLUSION: There is a need for vigilance for the possibility of dual pathologies in all specialties.

The supportive care needs of carers of people affected by cancer stationed in British Forces Germany.

Carers are central to the effective support of people affected by cancer. Little is known however about the specific support needs of carers of military personnel. This study aimed to determine the supportive care needs of unpaid carers within British Forces (including military/civilian personnel, their families and dependent adults) currently stationed in Germany. Qualitative semi-structured interviews were conducted with seven carers (six men and one woman) in three British army garrisons across Germany, to identify core aspects of the experience of caregiving in this environment. Analysis of interviews with carers was based on qualitative thematic and content analysis. Three key themes were identified: (1) impact on carers of their partners being diagnosed with cancer; (2) provision of support; and (3) challenges to accessing and obtaining support. Central issues pivot around the context of working and living in the armed forces and a lack of supportive care infrastructure. While drawing on a small sample size, this study nonetheless identifies that carers of people with cancer within the armed forces, who are stationed in Germany require a specialised and contextually specific set of services to address their supportive care needs.

Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.

BACKGROUND: There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha-2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. OBJECTIVES: To compare ketamine-medetomidine-guaifenesin with ketamine-medetomidine-midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. STUDY DESIGN: Prospective, randomised, blinded, crossover trial. METHODS: Fourteen weanlings received medetomidine 7 µg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5-10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P-values comparing treatment groups. RESULTS: Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). MAIN LIMITATIONS: No surgical stimulus was applied and study animals may not represent general horse population. CONCLUSION: Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine-medetomidine-midazolam.

Evaluation of conventional and real-time PCR assays for detection and differentiation of Spotted Fever Group Rickettsia in dog blood.

Spotted Fever Group Rickettsia is important cause of emerging and re-emerging infectious disease in people and dogs. Importantly, dogs can serve as sentinels for disease in people. Sensitive and specific diagnostic tests that differentiate among species of infecting Rickettsia are needed. The objective of this study was to develop a sensitive and specific PCR that differentiates SFG Rickettsia infecting dog blood. Conventional and real-time PCR assays were developed using primers that targeted a small region of the ompA gene. Their sensitivity, determined by testing a cloned target sequence in the presence of host DNA, was 15-30 and 5 copies of DNA, respectively. Testing of Rickettsia cultures and analysis of Rickettsia gene sequences deposited in GenBank verified DNA could be amplified and used to differentiate species. DNA from the blood of infected dogs was also tested. Importantly, Rickettsia DNA was detected before seroconversion in some dogs. The species of infecting Rickettsia was also identified. We conclude these assays may assist in the timely diagnosis of infection with SFG Rickettsia. They may also facilitate the discovery of novel SFG Rickettsia infecting dogs, and in the investigation of dogs as sentinels for emerging rickettsioses.

Involving people affected by cancer in research: a review of literature.

The purpose of the literature review was to find out why people affected by cancer have been involved in research; how they have been involved and the impact of their involvement. We used systematic methods to search for literature, applied inclusion and exclusion criteria, conducted a quality appraisal, selected relevant data from the included articles for analysis, and provided a narrative summary of these data. The literature shows that people affected by cancer, particularly women with breast cancer, have been involved in a range of research programmes, projects and initiatives especially in the USA, UK, Canada and Australia. Their involvement has impacted upon research design, accrual and response rates. There is increasing recognition of the need for an infrastructure, including formal recruitment procedures, training and mentoring, to support an agenda of involvement and a need to challenge the ethos of traditional research, which does not easily lend itself to this agenda. Further critique of the role of 'experiential knowledge' in research is required so that researchers and people affected by cancer can work in partnership.

A systematic review of the content and delivery of education in pulmonary rehabilitation programmes.

INTRODUCTION: Pulmonary rehabilitation (PR) is a core component of Chronic Obstructive Pulmonary Disease (COPD) management with well recognized benefits. While suggestions for educational content within pulmonary rehabilitation have been detailed in clinical guidance, it is unclear what educational content is delivered as part of pulmonary rehabilitation, who delivers it, and how it is delivered. METHODS: A systematic review was conducted to identify what educational content is delivered as part of pulmonary rehabilitation, how is this delivered and who delivers it. Databases were searched from 1981 to 2017 using multiple search terms related to "pulmonary rehabilitation" and "education". RESULTS: Fourteen studies were identified. This included 6 survey studies, 5 quasi-experimental studies and 3 RCTs. Five key topics that were consistently included within PR programmes were identified as: 1) Anxiety/depression and stress management. 2) Early recognition of signs of infection. 3) Dyspnea and symptom management. 4) Nutrition. 5) Techniques using inhalers and nebulizers. Broader topics such as welfare/benefits, sexuality, and advance care directives did not frequently feature. Only four studies used tools to measure knowledge or learning pre and post rehabilitation in an attempt to evaluate the effectiveness of the education delivered as part of PR. CONCLUSIONS: The delivery of education in PR programmes is variable and does not follow suggested educational topics. Education needs to take a patient centered motivational approach to ensure effective delivery. Further research into appropriate educational outcome measures are needed, in order to evaluate the changes in behaviour associated with education.

Prevalence of Vector-Borne Pathogens in Southern California Dogs With Clinical and Laboratory Abnormalities Consistent With Immune-Mediated Disease.

BACKGROUND: Studies investigating the prevalence of vector-borne pathogens in southern California dogs are limited. Occult infections might be misdiagnosed as idiopathic immune-mediated disease. HYPOTHESIS/OBJECTIVES: (1) To determine the prevalence of vector-borne pathogens in southern California dogs with compatible clinical findings using PCR and serologic panels and (2) to determine whether testing convalescent samples and repeating PCR on acute samples using the same and different gene targets enhance detection. ANIMALS: Forty-two client-owned dogs with clinical signs of vector-borne disease presenting to specialty practices in San Diego County. METHODS: Combined prospective and retrospective observational study. Forty-two acute and 27 convalescent samples were collected. Acute samples were prospectively tested for antibodies to Rickettsia, Ehrlichia, Bartonella, Babesia, Borrelia, and Anaplasma species. PCR targeting Ehrlichia, Babesia, Anaplasma, hemotropic Mycoplasma, and Bartonella species was also performed. Retrospectively, convalescent samples were tested for the same organisms using serology, and for Ehrlichia, Babesia, Anaplasma, and Bartonella species using PCR. Acute samples were retested using PCR targeting Ehrlichia and Babesia species. RESULTS: Evidence of exposure to or infection with a vector-borne pathogen was detected in 33% (14/42) of dogs. Ehrlichia and Babesia species were most common; each was identified in 5 dogs. Convalescent serologic testing, repeating PCR, and using novel PCR gene targets increased detection by 30%. CONCLUSIONS AND CLINICAL IMPORTANCE: Repeated testing using serology and PCR enhances detection of infection by vector-borne pathogens in dogs with clinical signs of immune-mediated disease. Larger prevalence studies of emerging vector-borne pathogens in southern California dogs are warranted.

Germline BCL-2 sequence variants and inherited predisposition to prostate cancer.

Apoptosis is an essential physiological process that regulates cellular proliferation. Here, we explored the effect of DNA sequence variation within the BCL-2 gene on prostate cancer susceptibility in three clinical populations, consisting of 428 African Americans, 214 Jamaicans and 218 European Americans. We observed a 70% reduced risk for prostate cancer among the European Americans who had possessed two copies of a promoter variant -938C/A. Additionally, common BCL-2 haplotypes appeared to influence prostate cancer risk; however, studies in larger data sets are needed to confirm our findings. Our data suggest that inherited BCL-2 variants may be associated with a decrease in prostate cancer susceptibility.

Urinary excretion of unmetabolized and phase II conjugates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans: relationship to cytochrome P4501A2 and N-acetyltransferase activity.

Cooking meat, fish, or poultry at high temperature gives rise to heterocyclic aromatic amines (HAAs), which may be metabolically activated to mutagenic or carcinogenic intermediates. The enzymes cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) are principally implicated in such biotransformations. We have determined the relationship between the activity of these two enzymes and the urinary excretion of unmetabolized and Phase II conjugates of the two HAAs MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in individuals fed a uniform diet containing high-temperature cooked meat. The subjects in the study ate meat containing known amounts of MeIQx and PhIP, and urine collections were made 0-12 and 12-24 h after a meal. MeIQx and PhIP were measured in urine after acid treatment that quantitatively hydrolyzes the Phase II conjugates to the respective parent amine. The extracts containing the HAAs were purified by immunoaffinity chromatography and analyzed by liquid chromatography using electrospray ionization-tandem mass spectrometry. The MeIQx content in the 0-12 h urine increased after acid hydrolysis by a factor of 3-21-fold. After acid treatment, the total amount of MelQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) excreted in the 0-12 h urine was 10.5 +/- 3.5% (mean +/- SD) of the dose, whereas the total amount of PhIP [unmetabolized plus acid-labile conjugate(s)] in the 0-12 h period was 4.3 +/- 1.7% (mean +/- SD) of the dose. The total amount of PhIP in the 12-24 h urine after acid treatment was 0.9 +/- 0.4% (mean +/- SD) of the dose. Linear regression analysis of the amounts of MeIQx and PhIP excreted in the 0-12 h period expressed as a percentage of the ingested dose, for all subjects, gave a low but significant correlation (r = 0.37, P = 0.005). Linear regression analyses showed that lower total MeIQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) in urine was associated with higher CYP1A2 activity, whereas total PhIP (unmetabolized plus conjugated) in urine showed no association to CYP1A2 activity. These results indicate that in humans, MeIQx metabolism and disposition are more strongly influenced by CYP1A2 activity than are those of PhIP. Linear regression analysis found no association between NAT2 activity and the levels (unmetabolized plus acid-labile conjugates) of MeIQx or PhIP excreted in urine.