RACS and its Fellows: a contribution to sustainable healthcare improvement in South East Asia.

The question of whether small non-government organizations with comparatively small budgets can make a substantial contribution to sustainable improvement in health care in low- and middle-income countries is crucial to funding global surgical projects. The Royal Australasian College of Surgeons and its Fellows have partnered with local organizations and clinicians to deliver a wide range of projects in South East Asia. These projects have proved sustainable and have increased healthcare capacity in these nations. This provides strong evidence that small non-government organizations such as the Royal Australasian College of Surgeons can make a major contribution to global surgeryI.

A CHIP fellow's transition into practice: Building a complex coronary therapeutics program.

BACKGROUND: Both the prevalence and complexity of coronary artery disease are on the rise in the United States, leading to a resurgence in novel techniques and equipment utilized to treat complex coronary disease. However, declining percutaneous coronary intervention (PCI) volumes and lack of formal post-graduate education opportunities have created a gap in treatment delivery for this patient population. Several complex, high-risk, and indicated PCI (CHIP) fellowships have been developed in an attempt to bridge this disparity. We present data from the first year of practice from a former CHIP fellow during development of a formal complex coronary therapeutics program. METHODS: Data was prospectively collected for PCIs performed during the first 12 months of practice for the lead author and compared to procedures performed in the 12 months prior to the study period. RESULTS: Out of 371 PCIs performed during the study period, 53.4% (198/371) were considered complex, including 126 chronic total occlusion (CTO) procedures. Compared to the previous 12 months, there was a significant increase in the number and complexity (median J-CTO score 2.1 vs. 1.3, p .04) of CTOs performed during the study period. CTO procedural characteristics and complication rates were similar to those previously published in large U.S. registries, with technical success in 93.4% (118/126) and procedural success in 85.7% (108/126). CONCLUSION: Following dedicated CHIP fellowship training and establishment of a formal CHIP program, procedural success and complication rates were achieved similar to those published in prior studies evaluating CTO PCI at high volume centers.

Effects of dietary inulin supplementation on the composition and dynamics of cecal microbiota and growth-related parameters in broiler chickens.

Inulin, a prebiotic, is an attractive alternative to antibiotic growth promoters in chickens. Dietary supplementation with inulin can improve growth performance, carcass yield, immune system activity, and serum biochemical parameters in chickens. A few studies investigated the impact of dietary inulin supplementation on chicken intestinal microbiota. In this study, we investigated how and why dietary supplementation with 1, 2, and 4% inulin can affect body weight gain, feed intake, food conversion rate, immunological parameters, serum biochemical parameters, and composition and dynamics of the cecal microbiota of Tegel broiler chickens using quantitative fluorescence in situ hybridization (qFISH). We showed that inulin inclusion has a negative effect on growth performance parameters before day 21 and a positive effect subsequently up to day 42. Quantitative FISH data revealed an age-dependent change in the cecal microbiota in the control broilers fed no inulin. Thus, relative abundances of Firmicutes and Actinobacteria decreased from 52.8 to 48.3% of total cells and from 8.7 to 1.4% at days 7 and 42, respectively. However, relative abundances of Bacteroidetes and Proteobacteria gradually increased from 9.3 to 26.9% of the total cells and from 10.7 to 21.1%, respectively, over the same periods. Inulin inclusion appeared to lower the relative abundances of Lactobacillus johnsonii and Bifidobacterium species at an early bird age, but it subsequently significantly (P < 0.05) increased their relative abundances. Such increases positively correlated with body weight gain of the birds, determined after day 21. Thus, dietary supplementation with inulin together with the addition of L. johnsonii and Bifidobacterium (B. gallinarum and B. pullorum) cultures at an early age may help overcome its early negative influence on growth performance. We believe that these findings can improve our knowledge on how inulin can change the intestinal microbiota of broiler chickens and help in developing an inulin feeding regime to optimize its beneficial role in chicken development.

Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.

Lysozyme is known to eliminate intestinal pathogens in poultry and improve their growth performance. However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear. Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue. A total of 400 1-d-old Di Gao chicks were allocated randomly to five groups, each consisting of four replicates (20 birds/group). The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks. Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens. No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found. However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism. Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples. Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.

Evaluating Information Quality of Revised Patient Education Information on Colonoscopy: It Is New But Is It Improved?

BACKGROUND: Previous research indicates that patients and their families have many questions about colonoscopy that are not fully answered by existing resources. We developed revised forms on colonoscopy bowel preparation and on the procedure itself. OBJECTIVE: As the goal of the revised materials is to have improved information relative to currently available information, we were interested in how revised information compared with what is currently available in terms of information quality and patient preference. METHODS: Participants were asked to review one at a time the Revised and Current versions of Colonoscopy bowel preparation instructions (study 1) and About Colonoscopy (study 2). The order of administration of the Revised and Current versions was randomly counterbalanced to assess order effects. Respondents rated each form along the following dimensions: amount, clarity, trustworthiness, readability and understandability, how new or familiar the information was, and reassurance. Participants were asked which form they preferred and 4 questions about why they preferred it. Open-ended questions asked participants to describe likes and dislikes of the forms and suggestions for improvement. RESULTS: The study 1 and study 2 samples were similar. Overall, in study 1, 62.4% preferred the Revised form, 28.1% preferred the Current form, and 6.7% were not sure. Overall, in study 2, 50.5% preferred the Revised form, 31.1% preferred the Current form, and 18.4% were not sure. Almost 75% of those in study 1 who received the Revised form first, preferred it, compared with less than half of those who received it first in study 2. In study 1, 75% of those without previous colonoscopy experience preferred the Revised form, compared with more than half of those who had previously undergone a colonoscopy. The study 1 logistic regression analysis demonstrated that participants were more likely to prefer the Revised form if they had viewed it first and had no previous experience with colonoscopy. In study 2, none of the variables assessed were associated with a preference for the Revised form. In comparing the 2 forms head-to-head, participants who preferred the Revised form in study 1 rated it as clearer compared with those who preferred the Current form. Finally, many participants who preferred the Revised form indicated in the open-ended questions that they liked it because it had more information than the Current form and that it had good visual information. CONCLUSIONS: This study is one of the first to evaluate 2 different patient education resources in a head-to-head comparison using the same participants in a within-subjects design. This approach was useful in comparing revised educational information with current resources. Moving forward, this knowledge translation approach of a head-to-head comparison of 2 different information sources could be taken to develop and refine information sources on other health issues.

Aqueous raw and ripe Pu-erh tea extracts alleviate obesity and alter cecal microbiota composition and function in diet-induced obese rats.

Pu-erh tea is attracting increased attention worldwide because of its unique flavor and health effects, but its impact on the composition and function of the gut microbiota remains unclear. The aim of this study was to investigate the effects of aqueous extracts of fermented (ripe) and non-fermented (raw) Pu-erh teas on the composition and function of the intestinal microbiota of rats with diet-induced obesity. We conducted a comparative metagenomic and meta-proteomic investigation of the microbial communities in cecal samples taken from obese rats treated with or without extracts of raw or ripe Pu-erh teas. By analyzing the composition and diversity of 16S rRNA amplicons and expression profiles of 814 distinct proteins, we found that despite differences in the chemical compositions of raw and ripe Pu-erh teas, administration of either tea at two doses (0.15- and 0.40-g/kg body weight) significantly (P < 0.05) increased microbial diversity and changed the composition of cecal microbiota by increasing the relative abundances of Firmicutes and decreasing those of Bacteroidetes. Community metabolic processes, including sucrose metabolism, glycolysis, and syntheses of proteins, rRNAs, and antibiotics were significantly (P < 0.05) promoted or had a tendency (0.10 < P < 0.05) to be promoted due to the enrichment of relevant enzymes. Furthermore, evidence at population, molecular, and metabolic levels indicated that polyphenols of raw Pu-erh tea and their metabolites potentially promote Akkermansia muciniphila growth by stimulating a type II and III secretion system protein, the elongation factor Tu, and a glyceraldehyde-3-phosphate dehydrogenase. This study provides new evidence for the prebiotic effects of Pu-erh tea.

Collecting data for global surgical indicators: a collaborative approach in the Pacific Region.

In 2015, the Lancet Commission on Global Surgery (LCoGS) recommended six surgical metrics to enable countries to measure their surgical and anaesthesia care delivery. These indicators have subsequently been accepted by the World Bank for inclusion in the World Development Indicators. With support from the Royal Australasian College of Surgeons and the Pacific Islands Surgical Association, 14 South Pacific countries collaborated to collect the first four of six LCoGS indicators. Thirteen countries collected all four indicators over a 6-month period from October 2015 to April 2016. Australia and New Zealand exceeded the recommended LCoGS target for all four indicators. Only 5 of 13 countries (38%) achieved 2-hour access for at least 80% of their population, with a range of 20% (Papua New Guinea and Solomon Islands) to over 65% (Fiji and Samoa). Five of 13 (38%) countries met the target surgical volume of 5000 procedures per 100 000 population, with six performing less than 1600. Four of 14 (29%) countries had at least 20 surgical, anaesthesia and obstetric providers in their workforce per 100 000 population, with a range of 0.9 (Timor Leste) to 18.5 (Tuvalu). Perioperative mortality rate was reported by 13 of 14 countries, and ranged from 0.11% to 1.0%. We believe it is feasible to collect global surgery indicators across the South Pacific, a diverse geographical region encompassing high-income and low-income countries. Such metrics will allow direct comparison between similar nations, but more importantly provide baseline data that providers and politicians can use in advocacy national health planning.

Effect of Ageratina adenophora invasion on the composition and diversity of soil microbiome.

In the present study, high throughput 16S rRNA gene sequencing was used to investigate soil invaded by the aggressive weed Ageratina adenophora to determine its effect on the species composition, distribution, and biodiversity of the bacterial communities. Soil samples from 12 micro-sites containing a monoculture of A. adenophora plants, mixtures of A. adenophora and different native plant species, and native species alone were studied. We found that the invasion of this weed resulted in a selection of bacteria belonging to phyla Acidobacteria and Verrucomicrobia and the lack of bacteria belonging to phyla Actinobacteria and Planctomycetes, but did not affect significantly the percentage abundances of members of other phyla. A similar bacterial population selection was also observed at genus or subgroup levels. The NO3--N level was an important factor affecting soil bacterial communities and contributed to the dominance of A. adenophora. However, the numbers of total bacterial species, and the diversity and structure of soil bacterial microbiome did not (P > 0.05) change significantly following invasion by this weed.

Capacity building for emergency care: Training the first emergency specialists in Myanmar.

OBJECTIVES: The Myanmar Ministry of Health has formed a partnership with Australasian professional colleges and international medical specialists to deliver a comprehensive programme for emergency care training and development. We describe this programme, emphasising the training of the first emergency specialists for Myanmar. METHODS: Eighteen junior specialists (EM18) joined a new postgraduate diploma in emergency medicine (Dip EM) through the University of Medicine (1) (UM1), Yangon. Diploma content included an introductory course, clinical rotations, 2 months in the emergency receiving centre (ERC) of the Yangon General Hospital (YGH) supervised by a volunteer Australasian emergency physician (FACEM), several short courses and an educational visit to Hong Kong. Curriculum and assessments comprising written and oral exams were devised and delivered by volunteer FACEMs and Hong Kong specialists. RESULTS: All EM18 completed the 18 month programme and passed the final assessments to graduate in February 2014. Course strengths included the supervised clinical rotation to the ERC and short course teaching on emergency medical, surgical, trauma, paediatric and disaster topics. The educational visit to Hong Kong enabled the EM18 to visualise more advanced EM systems that could be adapted to the Myanmar context. The participating international clinicians provided expert strategic advice on ED design, staffing, equipment, nursing and pre-hospital systems to leaders within universities, hospitals and the Ministry of Health. CONCLUSION: The first Myanmar postgraduate diploma in EM provides an example of collaborative and responsive clinical health capacity building in a context of very limited resources.

Transarterial embolisation with Guglielmi detachable coils in an infant with a vein of Galen aneurysmal malformation.

Vein of Galen aneurysmal malformation is a rare entity in the paediatric population. However, it is being recognised with increasing frequency due to better diagnostic techniques. Neonates usually present with congestive heart failure, while in older infants and children it tends to manifest with seizures, hydrocephalus, intracerebral or subarachnoid haemorrhages. We present a case of ruptured vein of Galen aneurysmal malformation in a 3-month-old baby boy treated by transarterial embolisation using Guglielmi detachable coils.

PGVL Hub: An integrated desktop tool for medicinal chemists to streamline design and synthesis of chemical libraries and singleton compounds.

PGVL Hub is an integrated molecular design desktop tool that has been developed and globally deployed throughout Pfizer discovery research units to streamline the design and synthesis of combinatorial libraries and singleton compounds. This tool supports various workflows for design of singletons, combinatorial libraries, and Markush exemplification. It also leverages the proprietary PGVL virtual space (which contains 10(14) molecules spanned by experimentally derived synthesis protocols and suitable reactants) for lead idea generation, lead hopping, and library design. There had been an intense focus on ease of use, good performance and robustness, and synergy with existing desktop tools such as ISIS/Draw and SpotFire. In this chapter we describe the three-tier enterprise software architecture, key data structures that enable a wide variety of design scenarios and workflows, major technical challenges encountered and solved, and lessons learned during its development and deployment throughout its production cycles. In addition, PGVL Hub represents an extendable and enabling platform to support future innovations in library and singleton compound design while being a proven channel to deliver those innovations to medicinal chemists on a global scale.

Contemporary challenges in mastocytosis.

Mastocytosis denotes a wide range of disorders characterized by having abnormal growth and accumulation of mast cells. Mast cells contain histamine and other inflammatory mediators, which have diverse actions within the body, and play crucial roles in acquired and innate immunity. The diverse actions of these inflammatory mediators can lead to puzzling symptoms in individuals with mastocytosis. These symptoms can include flushing, pruritus, nausea, vomiting, abdominal pain, diarrhea, vascular instability, and headache. These clinical features generally divide into cutaneous and systemic manifestations, giving rise to the two divisions of mastocytosis: cutaneous mastocytosis (CM) and systemic mastocytosis. CM has a highly favorable clinical prognosis. Systemic mastocytosis has a range of severity, with the milder forms often remaining chronic conditions, while the severe forms have rapid complex courses with poor prognoses. Generally, treatment is aimed at avoiding mast cell degranulation, inhibiting the actions of the constitutive mediators released by mast cells and, in severe cases, cytoreductive and polychemotherapeutic agents. Behavioral intervention includes avoidance of triggers, such as heat, cold, pressure, exercise, sunlight, and strong emotions. Treatment for released histamine and other inflammatory mediators includes H1 antihistamines, H2 antihistamines, proton pump inhibitors, anti-leukotriene agents, and injectible epinephrine (for possible anaphylaxis). For severe cases, treatment includes cytoreductive agents (interferon alpha, glucocorticoids, and cladribine) and polychemotherapeutic agents (daunomycin, etoposide, and 6-mercaptopurine). For very specific and severe cases, tyrosine kinase inhibitors, imatinib and midostaurine, have shown promise.

Coronary sinus to left atrial communication.

Congenital coronary sinus anomalies are rare in clinical practice, partly due to the lack of symptoms. We present a case of coronary sinus anomaly causing a right-to-left intracardiac shunt in a 46 years/old African American female with a past medical history of obstructive sleep apnea, diabetes mellitus, hypertension, coronary artery disease, and ischemic cardiomyopathy who presented with hypoxia. In the months prior to her presentation, she had suffered an inferior myocardial infarction with right ventricular involvement, as well as resulting severe tricuspid regurgitation. In conclusion, further investigations revealed a communication between the coronary sinus (CS) and left atrium (LA).

The immunobiology of systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by vascular damage, autoimmunity, and excessive collagen deposition. Despite advances in disease-specific treatment of other rheumatologic diseases, disease-targeted treatment in SSc continues to be elusive. In this review, our goal was to place the contemporary immunobiology of SSc in the perspective of clinical medicine. METHODS: We performed a PubMed search for the period from 1989 to 2007, using the keyword, "systemic sclerosis," resulting in a total of 9099 publications, including 1252 reviews. Articles were then selected based on their discussion of recent advances in the elusive pathogenesis of SSc. A final total of 259 articles were chosen for the review. RESULTS: The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. T-cells are a major component of the infiltrate in skin and lung, exhibiting increased expression of activation markers and showing signs of antigen-driven expansion. Preliminary data indicate that induction of oral tolerance with collagen, a target of SSc T-cell responses, is associated with clinical benefits. Although this suggests that T-cells participate in the pathogenesis of SSc, their precise role and antigen specificity largely remain to be elucidated. Defective numbers and functions of certain T-cell subsets, such as natural killer and gammadelta T-cells, may be involved in the failure to maintain tolerance. Other data suggest that gammadelta T-cells may themselves be effector cells in endothelial cell cytotoxicity. There are several lines of evidence for a pathogenic role of B-cells in SSc, in particular, through the production of autoantibodies. Antibody-dependent cell-mediated cytotoxicity is a primary pathogenic event in an animal model of SSc and is likely to be involved in human SSc. Nonetheless, there is as yet no convincing evidence for the pathogenicity of SSc-specific antibodies. SSc fibroblasts exhibit a specific phenotype characterized not only by excessive collagen production but also by increased responsiveness to and production of cytokines and chemokines. This phenotype is induced by a complex network of cytokines and chemokines but appears to be maintained in the absence of exogenous stimuli via the autocrine production of some of these factors by SSc fibroblasts themselves, particularly transforming growth factor, platelet-derived growth factor, monocyte chemoattractant protein 1, and interleukin-1. CONCLUSIONS: Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. Nonetheless, the possibility of achieving clinical benefits by inducing oral tolerance highlights the importance of characterizing SSc T-cell antigens. It is hoped that the identification of some of the key players in the induction and maintenance of the SSc fibroblast phenotype may yield new disease-targeted treatment regimens for patients with SSc.

Aspirin and nonsteroidal anti-inflammatory drug hypersensitivity.

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably, the clinician will encounter patients with clear indications for aspirin therapy but a history of aspirin sensitivity. Although protocols have been established for aspirin challenge and desensitization, it is not always an efficacious or safe procedure. This article reviews the different classifications of ASA/NSAIDs hypersensitivities to better guide the clinician in dealing with this patient population. History of crossrelativities between multiple NSAIDs implies a non-IgE-mediated process. Similarly, a history of monosensitivity to one NSAID implies an IgE-mediated process, although specific antibodies are often elusive. Despite the name, AERD can potentially be exacerbated by all cyclooxygenase (COX) inhibitors based on dose-dependent inhibition of COX-1. Aspirin desensitization can be achieved to improve both upper and lower respiratory symptoms for most patient with AERD. Aspirin desensitization can usually be achieved for those in need of the antiplatelet effects of aspirin, with the exception of those with aspirin-induced urticaria and baseline chronic urticaria. However, desensitization should only be attempted in those with stable coronary artery disease because the process of desensitization carries the inherent risk of anaphylaxis/anaphylactoid reaction, which may further increase cardiac demand and bring about ischemic injury. Therefore, desensitization is reserved until coronary artery disease is stabilized.

Potential adverse events with biologic response modifiers.

In recent years, an explosion of biologic response modifiers has entered the market to combat a variety of immune-mediated diseases. These can be in the form of recombinant cytokines, as in the case of interferon beta in the treatment of multiple sclerosis, or novel engineered antibodies constructed by combining non-human determinants with a human immunoglobulin scaffold, as in the case of omalizumab in the treatment of allergic asthma. More recently, completely human monoclonal antibodies have also been constructed. Adverse reactions related to these agents can be classified as expected or unexpected events. A number of case studies and a handful of randomized trials have demonstrated the potential toxicities with the use of biologic response modifiers. This article aims to review adverse event profiles of select biologic response modifiers for which the most data is available and are common to a rheumatology, allergy/immunology, and dermatology patient population.

Mastocytosis: the great masquerader.

Variants of mastocytosis can present with puzzling cutaneous and systemic symptoms and signs that can result in an erroneous diagnosis of idiopathic urticaria or idiopathic anayphylaxis. The molecular basis of mastocytosis is now better understood, with updated classification based on distinct growth factor and oncogene abnormalities. Elicitation of a full history and careful attention to the skin examination will usually provide the clinician enough information to deduce that the condition is not simply chronic idiopathic urticaria.

Safety of single versus multi-vessel angioplasty for patients with acute myocardial infarction and multi-vessel coronary artery disease: report from the New York State Angioplasty Registry.

BACKGROUND: The conventional strategy for primary angioplasty during acute myocardial infarction is angioplasty of the infarct-related vessel, even in patients with multi-vessel disease. Patients, however, often have significant lesions in multiple coronary arteries and a strategy for multi-vessel angioplasty during acute myocardial infarction has not been explored. The purpose of this study was to examine whether multi-vessel angioplasty is as safe as infarct-related vessel angioplasty in patients with multi-vessel coronary artery disease during acute myocardial infarction. METHODS: Using the 2000-2001 New York State Angioplasty Registry database, we compared the in-hospital clinical outcomes of patients with multi-vessel disease (>70% stenosis in at least two major coronary arteries), who underwent either multi-vessel angioplasty (n=632) or infarct-related vessel angioplasty (n=1350) within 24 h of acute myocardial infarction. Patients with previous myocardial infarction, angioplasty, bypass surgery, or cardiogenic shock were excluded. RESULTS: Patients in the multi-vessel angioplasty group were less likely to be female, to have peripheral vascular disease or diabetes. They had more complex lesions and were more likely to receive stents. In-hospital mortality was three-fold lower (0.8 versus 2.3%, P=0.018) in the multi-vessel angioplasty group. No differences were observed in other ischemic complications, renal failure, or length of stay. After multivariate analysis, multi-vessel angioplasty remained a significant predictor of lower in-hospital death (odds ratio=0.27, 95% confidence interval=0.08-0.90, P=0.03). CONCLUSIONS: Despite the added complexity of multi-vessel angioplasty, patients in this group had significantly lower in-hospital mortality. Therefore, a strategy of multi-vessel angioplasty during acute myocardial infarction may be safe compared with infarct-related angioplasty in selected patients.