Implementation Guide for Surveillance of Central Line Associated Bloodstream Infection -- [Consultation Edition]

The implementation guide for the surveillance of CLABSI in intensive care units (ICU) was produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care(ACSQHC), and endorsed by the ACSQHC HAI Advisory Committee. State surveillance units, the ACSQHC and the Australian and New Zealand Intensive Care Society (ANZICS) have representatives on the Technical Working Group, and have provided input into this document.

The hyperthermic patient

Concepts used in this chapter include: Thermoregulation:- Thermoregulation refers to the body’s sophisticated, multi-system regulation of core body temperature. This hierarchical system extends from highly thermo-sensitive neurons in the preoptic region of the brain proximate to the rostral hypothalamus, down to the brain stem and spinal cord. Coupled with receptors in the skin and spine, both central and peripheral information on body temperature is integrated to inform and activate the homeostatic mechanisms which maintain our core temperature at 37oC1. Hyperthermia:- An imbalance between the metabolic and external heat accumulated in the body and the loss of heat from the body2. Exertional heat stroke:- A disorder of excessive heat production coupled with insufficient heat dissipation which occurs in un-acclimated individuals who are engaging in over-exertion in hot and humid conditions. This phenomenon includes central nervous system dysfunction and critical dysfunction to all organ systems including renal, cardiovascular, musculoskeletal and hepatic functions. Non-exertional heat stroke:- In contrast to exertional heatstroke as a consequence of high heat production during strenuous exercise, non-exertional heatstroke results from prolonged exposure to high ambient temperature. The elderly, those with chronic health conditions and children are particularly susceptible.3 Rhabdomylosis:- An acute, sometimes fatal disease characterised by destruction of skeletal muscle. In exertional heat stroke, rhabdomylosis occurs in the context of strenuous exercise when mechanical and/or metabolic stress damages the skeletal muscle, causing elevated serum creatine kinease. Associated with this is the potential development of hyperkalemia, myoglobinuria and renal failure. Malignant hyperthermia:- Malignant hyperthermia is “an inherited subclinical myopathy characterised by a hypermetabolic reaction during anaesthesia. The reaction is related to skeletal muscle calcium dysregulation triggered by volatile inhaled anaesthetics and/or succinylcholine.”4 Presentation includes skeletal muscle rigidity, mixed metabolic and respiratory acidosis, tachycardia, hyperpyrexia, rhabdomylosis, hyperkalaemia, elevated serum creatine kinease, multi-organ failure, disseminated intravascular coagulation and death.5

The hypothermic patient

Concepts used in this chapter include: Thermoregulation:- Thermoregulation refers to the body’s sophisticated, multi-system regulation of core body temperature. This hierarchical system extends from highly thermo-sensitive neurons in the preoptic region of the brain proximate to the rostral hypothalamus, down to the brain stem and spinal cord. Coupled with receptors in the skin and spine, both central and peripheral information on body temperature is integrated to inform and activate the homeostatic mechanisms which maintain our core temperature at 37oC.1 Body heat is lost through the skin, via respiration and excretions. The skin is perhaps the most important organ in regulating heat loss. Hyporthermia:- Hypothermia is defined as core body temperature less than 350C and is the result of imbalance between the body’s heat production and heat loss mechanisms. Hypothermia may be accidental, or induced for clinical benefit i.e: neurological protection (therapeutic hypothermia). External environmental conditions are the most common cause of accidental hypothermia, but not the only causes of hypothermia in humans. Other causes include metabolic imbalance; trauma; neurological and infectious disease; and exposure to toxins such as organophosphates. Therapeutic Hypothermia:- In some circumstances, hypothermia can be induced to protect neurological functioning as a result of the associated decrease in cerebral metabolism and energy consumption. Reduction in the extent of degenerative processes associated with periods of ischaemia such as excitotoxic cascade; apoptotic and necrotic cell death; microglial activation; oxidative stress and inflammation associated with ischaemia are averted or minimised.2 Mild hypothermia is the only effective treatment confirmed clinically for improving the neurological outcomes of patient’s comatose following cardiac arrest.3

Grunt language versus accent : the perceived communication barriers between international medical graduates and patients in Central Wheatbelt catchments

Due to the chronic shortages of GPs in Australian rural and remote regions, considerable numbers of international medical graduates (IMG) have been recruited. IMG experience many difficulties when relocating to Australia with one of the most significant being effective GP-patient communication. Given that this is essential for effective consultation it can have a substantial impact on health care. A purposive sample of seven practising GPs (five IMG, two Australian-trained doctors (ATD)) was interviewed using a semistructured face-to-face interviewing technique. GPs from Nigeria, Egypt, United Kingdom, India, Singapore and Australia participated. Interviews were transcribed and then coded. The authors used qualitative thematic analysis of interview transcripts to identify common themes. IMG-patient communication barriers were considered significant in the Wheatbelt region as identified by both IMG and ATD. ATD indicated they were aware of IMG-patient communication issues resulting in subsequent consults with patients to explain results and diagnoses. Significantly, a lack of communication between ATD and IMG also emerged, creating a further barrier to effective communication. Analysis of the data generated several important findings that rural GP networks should consider when integrating new IMG into the community. Addressing the challenges related to cross-cultural differences should be a priority, in order to enable effective communication. More open communication between ATD and IMG about GP-patient communication barriers and education programs around GP-patient communication would help both GP and patient satisfaction.

Natural disaster risk-informed for a better public infrastructure asset planning in Indonesian Central Government

The natural disasters incident that frequently hit Indonesia are floods, severe droughts, tsunamis, earth-quakes, volcano, eruptions, landslides, windstorm and forest fires. The impact of those natural disasters are significantly severe and affecting the quality of life of the community due to the breakdown of the public as-sets as one source to deliver public services. This paper is aimed to emphasis the importance of natural disaster risk-informed in relation to public asset management in Indonesian Central Government, particularly in asset planning stage where asset decision is made as the gate into the whole public asset management processes. A Case study in the Ministry of Finance Indonesia as the central government public asset manager and in 5 (five) line ministries/governmental agencies as public asset users was used as the approach to achieved the research objective. The case study devoured three data collection techniques i.e. interviews, observations and document archival which will be analysed by a content analysis approach. The result of the study indicates that Indonesian geographical position exposing many of public infra-structure assets as a high vulnerability to natural disasters. Information on natural-disaster trends and predictions to identify and measure the risks are available, however, such information are not utilise and integrated to the process of public infrastructure asset planning as the gate to the whole public asset management processes. Therefore, in order to accommodate and incorporate this natural disaster risk-information into public asset management processes, particularly in public asset planning, a public asset performance measurements framework should be adopted and applied in the process as one sources in making decision for infrastructure asset planning. Findings from this study provide useful input for the Ministry of Finance as public asset manager, scholars and private asset management practitioners in Indonesia to establish natural disaster risks awareness in public infrastructure asset management processes.

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs

Migraine is a debilitating neurovascular disorder, with a substantial genetic component. The exact cause of a migraine attack is unknown; however cortical hyperexcitability is thought to play a role. As Gamma-aminobutyric Acid (GABA) is the major inhibitory neurotransmitter in the brain, malfunctioning of this system may be a cause of the hyperexcitability. To date, there has been limited research examining the gene expression or genetics of GABA receptors in relation to migraine. The aim of our study was to determine if GABA receptors play a role in migraine by investigating their gene expression using profile in migraine affected individuals and non-affected controls by Q-PCR. Gene expression of GABA(A) receptor subunit isoforms (GABRA3, GABRB3, GABRQ) and GABA(B) receptor 2 (GABBR2) was quantified in mRNA obtained from peripheral blood leukocytes from 28 migraine subjects and 22 healthy control subjects. Analysis of results showed that two of the tested genes, GABRA3 and GABBR2, were significantly down regulated in migraineurs (P=0.018; P=0.017), compared to controls. Results from the other tested genes did not show significant gene expression variation. The results indicate that there may be specific GABA receptor gene expression variation in migraine, particularly involving the GABRA3 and GABBR2 genes. This study also identifies GABRA3 and GABBR2 as potential biomarkers to select migraineurs that may be more responsive to GABA agonists with future investigations in this area warranted.

Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility

Background Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors) or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated. Methods The association of polymorphic variants of GRIA1-GRIA4 genes which encode for the four subunits (GluR1-GluR4) of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor for glutamate was tested in migraineurs with and without aura (MA and MO) and healthy controls. Results Two variants in the regulative regions of GRIA1 (rs2195450) and GRIA3 (rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in GRIA1 gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of GRIA1 and GRIA3 genes in different conditions. Conclusions This study represents the first genetic evidence of a link between glutamate receptors and migraine.

Investigation of the [−/A]8 and C1236T genetic variations within the human toll-like receptor 3 gene for association with multiple sclerosis

Multiple sclerosis (MS) is a serious cause of neurological disability among young adults. The clinical course remains difficult to predict, and the pathogenesis of the disease is still modestly understood. Autoimmunity is thought to be a key aspect of the disease, with autoreactive T cells thought to mediate central nervous system (CNS) inflammation to some extent. Toll-like receptors are known to mediate cellular recognition of pathogens by way of patterns of molecular presentation. Toll-like receptor 3 is coded by the gene TLR3 and is recognized as an important factor in virus recognition and is known to be involved in the expression of neuroprotective mediators. We set out to investigate two variations within the TLR3 gene, an 8 bp insertion-deletion \[-/A](8) and a single base-pair variation C1236T, in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We used capillary gel electrophoresis and TaqMan genotyping assay techniques to resolve genotypes for each marker, respectively. Our work found no significant difference between frequencies for TLR3 \[-/A](8) by genotype (chi(2)=1.03, p=0.60) or allele (chi(2)=1.09, p=0.30). Similarly, we found no evidence for the association of TLR3 C1236T by genotype (chi(2)=0.35, p=0.84) or allele frequency (chi(2)=0.31, p=0.58). This work reveals no evidence to suggest that these markers are associated with MS in the tested population. Although the role of TLR3 and the wider toll-like receptor family remain significant in neurological and CNS inflammatory disorders, our current work does not support a role for the two tested variants in this gene with regard to MS susceptibility.

Heparan sulfate proteoglycans, tumour progression and the cancer stem cell niche

The cancer stem cell hypothesis states that tumours arise from cells with the ability to self-renew and differentiate into multiple cell types, and that these cells persist in tumors as a distinct population that can cause disease relapse and hence metastasis. The crux of this hypothesis is that these cells are the only cells capable of, by themselves, giving rise to new tumours. What proportion of a tumour consists of these stem cells, where are they localised, how are they regulated, and how can we identify them? The stromal cells embedded within the extracellular matrix (ECM) not only provide a scaffold but also produce ECM constituents for use by stem cells. Heparan sulfate proteoglycans (HSPGs) are ubiquitous to this cell niche and interact with a large number of ligands including growth factors, their receptors, and ECM structural components. It is still unclear whether ECM degradation and subsequent metastasis is a result of proteases produced by the tumour cells themselves or by cells within the stromal compartment. The identification of the cellular origin of cancer stem cells along with microenvironmental changes involved in the initiation, progression and the malignant conversion of all cancers is critical to the development of targeted therapeutics. As ubiquitous members of the ECM microenvironment and hence the cancer cell niche, HSPGs are candidates for a central role in these processes.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Postnatal depression in Central Vietnam

Postnatal depression (PND) is a significant global health issue, which not only impacts maternal wellbeing, but also infant development and family structures. Mental health disorders represent approximately 14% of global burden of disease and disability, including low and middle-income countries (LMIC), and PND has direct relevance to the Millennium Development Goals of reducing child mortality, improving maternal health, and creating global partnerships (United Nations, 2012; Guiseppe, Becker & Farmer, 2011). Emerging evidence suggests that PND in LMIC is similar to, or higher than in high-income countries (HIC), however, less than 10% of LMIC have prevalence data available (Fisher, Cabral de Mello, & Izutsu 2009; Lund et al., 2011). Whilst a small number of studies on maternal mental disorders have been published in Vietnam, only one specifically focuses on PND in a hospital-based sample. Also, community based mental health studies and information on mental health in rural areas of Vietnam is still scarce. The purpose of this study was to determine the prevalence of PND, and its associated social determinants in postnatal women in Thua Thien Hue Province, Central Vietnam. In order to identify social determinants relevant to the Central Vietnamese context, two qualitative studies and one community survey were undertaken. Associations between maternal mental health and infant health outcomes were also explored. The study was comprised of three phases. Firstly, iterative, qualitative interviews with Vietnamese health professionals (n = 17) and postpartum women (n = 15) were conducted and analysed using Kleinman's theory of explanatory models to identify narratives surrounding PND in the Vietnamese context (Kleinman, 1978). Secondly, a participatory concept mapping exercise was undertaken with two groups of health professionals (n = 12) to explore perceived risk and protective factors for postnatal mental health. Qualitative phases of the research elucidated narratives surrounding maternal mental health in the Vietnamese context such as son preference, use of traditional medicines, and the popularity of confinement practices such as having one to three months of complete rest. The qualitative research also revealed the construct of depression was not widely recognised. Rather, postpartum changes in mood were conceptualised as a loss of 'vital strength' following childbirth or 'disappointment'. Most women managed postpartum changes in mood within the family although some sought help from traditional medicine practitioners or biomedical doctors. Thirdly, a cross-sectional study of twelve randomly selected communes (six urban, six rural) in Thua Thien Hue Province was then conducted. Overall, 465 women with infants between 4 weeks and six months old participated, and 431 questionnaires were analysed. Women from urban (n = 216) and rural (n = 215) areas participated. All eligible women completed a structured interview about their health, basic demographics, and social circumstances. Maternal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) as a continuous variable. Multivariate generalised linear regression was conducted using PASW Statistics version 18.0 (2009). When using the conventional EPDS threshold for probable depression (EPDS score ~ 13) 18.1% (n = 78) of women were depressed (Gibson, McKenzie-McHarg, Shakespeare, Price & Gray, 2009). Interestingly, 20.4% of urban women (n = 44) had EPDS scores~ 13, which was a higher proportion than rural women, where 15.8% (n = 34) had EPDS scores ~ 13, although this difference was not statistically significant: t(429) = -0.689, p = 0.491. Whilst qualitative narratives identified infant gender and family composition, and traditional confinement practices as relevant to postnatal mood, these were not statistically significant in multivariate analysis. Rather, poverty, food security, being frightened of your husband or family members, experiences of intimate partner violence and breastfeeding difficulties had strong statistical associations. PND was also associated with having an infant with diarrhoea in the past two weeks, but not infant malnutrition or acute respiratory infections. This study is the first to explore maternal mental health in Central Vietnam, and provides further evidence that PND is a universally experienced phenomenon. The independent social risk factors of depressive symptoms identified such as poverty, food insecurity, experiences of violence and powerlessness, and relationship adversity points to women in a context of social suffering which is relevant throughout the world (Kleinman, Das & Lock, 1997). The culturally specific risk factors explored such as infant gender were not statistically significant when included in a multivariable model. However, they feature prominently in qualitative narratives surrounding PND in Vietnam, both in this study and previous literature. It appears that whilst infant gender may not be associated with PND per se, the reactions of close relatives to the gender of the baby can adversely affect maternal wellbeing. This study used a community based participatory research approach (CBPR) (Israel.2005). This approach encourages the knowledge produced to be used for public health interventions and workforce training in the community in which the research was conducted, and such work has commenced. These results suggest that packages of interventions for LMIC devised to address maternal mental health and infant wellbeing could be applied in Central Vietnam. Such interventions could include training lay workers to follow up postpartum women, and incorporating mental health screening and referral into primary maternal and child health care (Pate! et al., 2011; Rahman, Malik, Sikander & Roberts, 2008). Addressing the underlying social determinants of PND through poverty reduction and violence elimination programs is also recommended.

Characteristics of on-road driving performance of persons with central vision loss who use bioptic telescopes

Purpose. To compare the on-road driving performance of visually impaired drivers using bioptic telescopes with age-matched controls. Methods. Participants included 23 persons (mean age = 33 ± 12 years) with visual acuity of 20/63 to 20/200 who were legally licensed to drive through a state bioptic driving program, and 23 visually normal age-matched controls (mean age = 33 ± 12 years). On-road driving was assessed in an instrumented dual-brake vehicle along 14.6 miles of city, suburban, and controlled-access highways. Two backseat evaluators independently rated driving performance using a standardized scoring system. Vehicle control was assessed through vehicle instrumentation and video recordings used to evaluate head movements, lane-keeping, pedestrian detection, and frequency of bioptic telescope use. Results. Ninety-six percent (22/23) of bioptic drivers and 100% (23/23) of controls were rated as safe to drive by the evaluators. There were no group differences for pedestrian detection, or ratings for scanning, speed, gap judgments, braking, indicator use, or obeying signs/signals. Bioptic drivers received worse ratings than controls for lane position and steering steadiness and had lower rates of correct sign and traffic signal recognition. Bioptic drivers made significantly more right head movements, drove more often over the right-hand lane marking, and exhibited more sudden braking than controls. Conclusions. Drivers with central vision loss who are licensed to drive through a bioptic driving program can display proficient on-road driving skills. This raises questions regarding the validity of denying such drivers a license without the opportunity to train with a bioptic telescope and undergo on-road evaluation.

Identification of GABA receptors in chick retinal pigment epithelium

Purpose: The retinal pigment epithelium (RPE) is a multifunctional, monolayer of cells located between the neural retina and the choroicapillaris. γ-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the retina and GABA receptors are known to be present in chick retina, sclera and cornea. There is a report of genes involved in GABA receptor signaling being expressed in human RPE, however, whether GABA receptors are present in chick RPE is unknown. Methods: Real time PCR and western blot were used to determine the expression of GABA receptors (alpha1 GABAA, GABABR2, and rho1 GABAC receptors) in isolated chicken RPE. Immunofluorescence using antibodies against one of the GABA receptor sub-types was used to determine receptor localization. Results: Both real-time PCR and western blot demonstrated that alpha1 GABAA, GABABR2 and rho1 GABAC receptors were expressed in isolated chick RPE. Immunofluorescence further demonstrated that GABA receptors were localized to the cell membrane and plasma of RPE cells. Conclusions: Alpha1 GABAA, GABABR2 and rho1 GABAC receptors were expressed in chick RPE. The purpose of the GABA receptors within the RPE remains to be explored.