Contribution of general medicine to perioperative and consultative care: an Australian metropolitan teaching hospital experience.

Little is known about the contribution of general medicine to perioperative and consultative care in Australia. A descriptive observational study was undertaken at a quaternary institution to evaluate the characteristics of perioperative and nonoperative consultations undertaken by general medicine. Results demonstrated patterns of engagement within a 'traditional' model of perioperative care and highlighted several opportunities for a redesign to a more proactive and collaborative cross-disciplinary model.

Defining immune correlates during latent and active chlamydial infection in sheep.

Ovine enzootic abortion (OEA) caused by the obligate intracellular bacterial pathogen Chlamydia abortus (C. abortus), is an endemic disease in most sheep-rearing countries worldwide. Following infection, C. abortus establishes a complex host-pathogen interaction with a latent phase in non-pregnant sheep followed by an active disease phase in the placenta during pregnancy leading to OEA. Improved knowledge of the host-pathogen interactions at these different phases of disease will accelerate the development of new diagnostic tests and vaccines to control OEA. Current evidence indicates that cellular immunity is essential for controlling C. abortus infection. We have previously described a model of mucosal (intranasal) infection of non-pregnant sheep with C. abortus that replicates the latent and active phases of OEA. We have investigated antigen-specific recall responses of peripheral blood mononuclear cells (PBMC) in sheep infected with C. abortus via the intranasal route to determine how these change during the latent and active phases of disease. By analysing cytokines associated with the major CD4+ve Thelper (Th) cell subsets (Interferon-gamma (IFN-γ)/Th1; Interleukin (IL)-4/Th2; IL-17A/Th17; IL-10/Tregulatory), we show that there is selective activation of PBMC producing IFN-γ and/or IL-10 during the latent phase following infection. These cytokines are also elevated during the active disease phase and while they are produced by sheep that are protected from OEA, they are also produced by sheep that abort, highlighting the difficulties in finding specific cellular immunological correlates of protection for complex intracellular pathogens.

Inflammatory infiltration into placentas of Neospora caninum challenged cattle correlates with clinical outcome of pregnancy.

Infection with Neospora caninum stimulates host cell-mediated immune responses, which may be responsible for placental damage leading to bovine abortion. The aim of this study was to compare immune responses in the bovine placenta, following experimental infection in different stages of pregnancy. Placentomes were examined by immunohistochemistry and inflammation in early gestation was generally moderate to severe, particularly in the placentas carrying non-viable foetuses, whereas it was milder in later stages, mainly characterised by the presence of CD3+, CD4+ and γδ T-cells. This distinctive cellular immune response may explain the milder clinical outcome observed when animals are infected in later gestation.

Top Ten Tips Palliative Care Clinicians Should Know About the Psychological Aspects of Palliative Care Encounters.

Palliative care clinicians enhance the illness experiences of patients and their families through building therapeutic relationships. Many psychological concepts underlie a clinician's approach to a specific patient. Through high-yield tips, this article highlights ten selected psychological elements that palliative care clinicians often use to support patients. As we all (both clinicians and patients) bring our own histories and unique biographies to the work of palliative care, a more explicit focus on the psychological aspects of this work can enhance our own experience and efficacy as providers. With a thoughtful focus on the psychological aspects of how we engage with patients, palliative care clinicians can offer a more meaningful therapeutic encounter.

High rate of transplacental infection and transmission of Neospora caninum following experimental challenge of cattle at day 210 of gestation.

In order to investigate the pathogenesis of neosporosis following a primary infection in late pregnancy, cattle were subcutaneously challenged with 5 × 108Neospora caninum (NC1 isolate) tachyzoites at day 210 of gestation and serial necropsies were then carried out at 14, 28, 42 and 56 days post-infection (dpi). No abortions occurred and all the foetuses were viable at the time of euthanasia. There was a high rate of vertical transmission, as parasites were detected by immunohistochemical labelling and PCR in all the foetuses from 28 dpi. Focal necrotic lesions were observed in the placentomes of the placenta from 28 dpi and showed resolution during later time points, denoted by infiltration of inflammatory cells at 42 dpi and fibrosis at 56 dpi. Foetuses at 28 and 42 dpi showed scarce and isolated lesions which are unlikely to represent a threat to foetal viability. No lesions were observed in the foetuses at 14 or 56 dpi suggesting control of the infection and resolution of the lesions by maternal and foetal immune responses. Once infection was established, it could not be cleared from the host and vertical transmission of the parasite occurred in all infected hosts. Parasite was detected in the placenta at 28 dpi, while in previous experimental infections of cattle at day 70 and 140 of gestation using the same challenge model, it was already present at day 14 post infection. This suggests that a change in the maternal immune response plays a crucial role in limiting the initial infection during the last term of pregnancy.

Maternal and foetal immune responses of cattle following an experimental challenge with Neospora caninum at day 70 of gestation.

The immune responses of pregnant cattle and their foetuses were examined following inoculation on day 70 of gestation either intravenously (iv) (group 1) or subcutaneously (sc) (group 2) with live NC1 strain tachyzoites or with Vero cells (control) (group 3). Peripheral blood mononuclear cell (PBMC) responses to Neospora antigen and foetal viability were assessed throughout the experiment. Two animals from each group were sacrificed at 14, 28, 42 and 56 days post inoculation (pi). At post mortem, maternal lymph nodes, spleen and PBMC and when possible foetal spleen, thymus and PBMC samples were collected for analysis. Inoculation with NC1 (iv and sc) lead to foetal deaths in all group 1 dams (6/6) and in 3/6 group 2 dams from day 28pi; statistically significant (p ≤ 0.05) increases in cell-mediated immune (CMI) responses including antigen-specific cell proliferation and IFN-γ production as well as increased levels of IL-4, IL-10 and IL-12 were observed in challenged dams compared to the group 3 animals. Lymph node samples from the group 2 animals carrying live foetuses showed greater levels of cellular proliferation as well as significantly (p ≤ 0.05) higher levels of IFN-γ compared to the dams in group 2 carrying dead foetuses. Foetal spleen, thymus and PBMC samples demonstrated cellular proliferation as well as IFN-γ, IL-4, IL-10 and IL-12 production following mitogenic stimulation with Con A from day 14pi (day 84 gestation) onwards. This study shows that the generation of robust peripheral and local maternal CMI responses (lymphoproliferation, IFN-γ) may inhibit the vertical transmission of the parasite.

Hydration and water intake practices of commercial long-distance drivers in Ghana: what do they know and why does it matter?

BACKGROUND: The World Health Organization indicates that hydration is indispensable to human life. A long-period of dehydration can result in fatigue, drowsiness and mental confusion which can result in committing serious blunders. For commercial drivers, however, these blunders can be life-threatening and their hydration cannot be overemphasized. AIM: This study was therefore undertaken to assess the water intake practices of Commercial Long-Distance drivers (CLDDs). The study was also aimed at assessing their knowledge levels on the role of water in promoting a healthy body and the consequences of dehydration. SETTING: CLDDs in Ghana who ply between Accra - Cape Coast - Takoradi or Accra - Kumasi. METHODS: A cross-sectional study which involved 256 CLDDs was conducted at six (6) commercial bus stations in Accra and Cape Coast from December 2019 to January 2020. Structured questionnaires were administered to obtain socio-demographic and water intake practices of CLDDs. SPSS was used to generate descriptive statistics based on the data collected. RESULTS: A high proportion (57.8%) of the CLDDs reported that they drunk about 2500ml-3000ml of water on a daily basis. Most (53.1%) relied on their thirst feeling to prompt them to drink water. A little over half (51.1%) consumed energy drinks believed to hydrate the body. A major barrier to drinking water regularly was to avoid frequent stop-overs to use the washroom while travelling. CONCLUSION: The findings reveal concerns about knowledge gaps with regard to the importance of water consumption and barriers to adequate drinking of water among CLDDs. Findings also suggest that many CLDDs relied on their thirst perceptions to prompt them to drink water. Health Education programmes targeting CLDDs should include conveying the importance of water intake and healthy hydration practices for optimal physical and cognitive performance.

An Emergency Department Clinical Algorithm to Increase Early Palliative Care Consultation: Pilot Project.

Introduction: The emergency department (ED) is a primary entry point of hospitals but does not have a system to identify and consult palliative care (PC) early in patients who meet criteria. Objectives: To determine the measurable effects of an ED PC consultation on patients who meet criteria, hypothesizing that ED PC consultation would lead to decreased average length of stay (ALOS), average direct cost per patient, decreased number of surgeries, and radiological tests performed per patient. Materials and Methods: A physician-led data-driven evidence-based algorithm was designed and piloted with implementation in two hospitals during January-March 2019 in Orlando, FL. A retrospective review of health record data was completed, comparing patients receiving PC consultation ordered in the ED versus those ordered after admission. Results: ED patients (n = 662) met PC criteria. PC consultation was ordered in ED for 80 (12.1%) cases. The following outcomes were lower for patients who received ED PC consultation than those who did not: ALOS by 6.4 days (6.74 vs. 13.14 days; p < 0.001), in-hospital mortality (12.5% vs. 19.1%; p = 0.11), surgery (11% vs. 37%; p < 0.01), radiological tests per patient (4.01 vs. 10.57; p < 0.001), and average direct cost per patient ($7,193 vs. $22,354). However, 30-day hospital revisit rates were relatively higher in those who did receive ED PC consultation than those who did not (20% vs. 13% p = 0.15). Conclusions: In this pilot project, PC patients can be identified in the ED with an algorithm that leads to earlier consultation and improved patient outcomes. Larger research trials are needed to replicate this strategy and results.

Stroke incidence and subtypes in Aboriginal people in remote Australia: a healthcare network population-based study.

OBJECTIVES: We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities. DESIGN: A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014. SETTING: Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km2. PARTICIPANTS: 161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of first-ever stroke, overall (all events) stroke and in-hospital death. RESULTS: Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p<0.001), and age-standardised stroke incidence was threefold that of non-Aboriginal patients (153 vs 51 per 100 000, incidence rate ratio 3.0, 95% CI 2 to 4). The rate ratios for the overall rate of stroke (first-ever and recurrent) were similar. In Aboriginal patients aged <55 years, the incidence of ischaemic stroke was 14-fold greater (95% CI 4 to 45), and intracerebral haemorrhage 19-fold greater (95% CI 3 to 142) than in non-Aboriginal patients. Crude prevalence of diabetes mellitus (70.3% vs 34.0%, p<0.001) and hypercholesterolaemia (68.9% vs 51.1%, p=0.049) was greater, and age-standardised in-hospital deaths were fivefold greater (35 vs 7 per 100 000, 95% CI 2 to 11) in Aboriginal patients than in non-Aboriginal patients. CONCLUSIONS: Stroke incidence (both subtypes) and in-hospital deaths for remote Aboriginal Australians are dramatically greater than in non-Aboriginal people, especially in patients aged <55 years.

Ovine toxoplasmosis.

Congenital infection with Toxoplasma gondii is an important cause of abortion in sheep worldwide. The cat is the definitive host of the parasite, and infected cats may shed millions of oocysts in their faeces resulting in extensive environmental contamination and an important source of infection for grazing herbivorous animals. Studies looking at development of specific antibodies in sheep, as an indicator of exposure to T. gondii, have shown that there is an increase in seroprevalence associated with age indicating that most infections in sheep occur following birth. The stage of gestation when transplacental transmission of T. gondii to the developing foetus occurs is critical in determining the clinical outcome. The importance of endogenous transplacental transmission in persistently infected ewes and its clinical importance is a subject of current debate. Ewes infected prior to mating develop immune responses that help protect against disease in a subsequent pregnancy and also against experimental challenge administered during pregnancy. Both innate and adaptive immune responses are activated following T. gondii infection and experiments involving the chronic cannulation of peripheral lymph nodes in sheep have allowed the dynamics of the immune responses to be analysed in real time. A live vaccine, Toxovax is the only commercially available vaccine worldwide to protect against congenital toxoplasmosis.

Veterinary vaccines against Toxoplasma gondii.

Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

Social Media Consequences of Pediatric Death.

Social media is an important access point for engagement of children and adolescents. For individuals with a life-limiting illness or serving as the caregiver for an ill child, social media can be a helpful outlet for support and information gathering. It has democratized the process of being remembered through providing an ongoing account of thoughts, pictures, and videos that theoretically live on forever via a digital legacy. Providers should be familiar with how this new generation uses social media during their illness, after death, and in the bereavement process.

Toxoplasma gondii and ovine toxoplasmosis: new aspects of an old story.

Ovine toxoplasmosis, caused by the intracellular protozoan parasite Toxoplasma gondii, was first described in 1954 and while the incidence of ovine infection is difficult to define, it has been reported that in the UK it is responsible for between 1 and 2% of neonatal losses per annum. Recent reports have suggested that sheep persistently infected with T. gondii may pass infection to the fetus in subsequent pregnancies more readily than previously thought. These data show a high proportion of both successful and failed pregnancies in sheep to be positive by PCR for T. gondii with a tendency for samples from certain genetic lines of Charollais sheep more likely to be positive than samples from other lines, suggesting that some sheep have a particular genetic susceptibility to T. gondii.

Striatal Neuropeptides Enhance Selection and Rejection of Sequential Actions.

The striatum is the primary input nucleus for the basal ganglia, and receives glutamatergic afferents from the cortex. Under the hypothesis that basal ganglia perform action selection, these cortical afferents encode potential "action requests." Previous studies have suggested the striatum may utilize a mutually inhibitory network of medium spiny neurons (MSNs) to filter these requests so that only those of high salience are selected. However, the mechanisms enabling the striatum to perform clean, rapid switching between distinct actions that form part of a learned action sequence are still poorly understood. Substance P (SP) and enkephalin are neuropeptides co-released with GABA in MSNs preferentially expressing D1 or D2 dopamine receptors respectively. SP has a facilitatory effect on subsequent glutamatergic inputs to target MSNs, while enkephalin has an inhibitory effect. Blocking the action of SP in the striatum is also known to affect behavioral transitions. We constructed phenomenological models of the effects of SP and enkephalin, and integrated these into a hybrid model of basal ganglia comprising a spiking striatal microcircuit and rate-coded populations representing other major structures. We demonstrated that diffuse neuropeptide connectivity enhanced the selection of unordered action requests, and that for true action sequences, where action semantics define a fixed structure, a patterning of the SP connectivity reflecting this ordering enhanced selection of actions presented in the correct sequential order and suppressed incorrect ordering. We also showed that selective pruning of SP connections allowed context-sensitive inhibition of specific undesirable requests that otherwise interfered with selection of an action group. Our model suggests that the interaction of SP and enkephalin enhances the contrast between selection and rejection of action requests, and that patterned SP connectivity in the striatum allows the "chunking" of actions and improves selection of sequences. Efficient execution of action sequences may therefore result from a combination of ordered cortical inputs and patterned neuropeptide connectivity within striatum.

Veterinary and medical aspects of abortion in Danish sheep.

The Danish sheep population totals around 144,000 animals, but little is known of the causes and prevalance of diseases. This study focuses on the causes of abortion in Danish sheep. During one breeding season, aborted foetuses and stillbirths with signs of intrauterine death or malformation were submitted for laboratory examination from a population of 3,758 breeding ewes. Samples from 24 incidents of abortion and 21 ewes delivering malformed lambs or lambs with ante partum decomposition were submitted. A specific aetiology was established in 66.7% and 14.3% of the cases, respectively. Bacterial pathogens were the most prevalent cause of abortion. Several of the abortifacients were zoonotic microorganisms, for example Listeria monocytogenes, Campylobacter fetus subsp. fetus, Yersinia pseudotuberculosis and Toxoplasma gondii. The identified microorganisms probably represent the most common causes of abortion in Danish sheep but occurrence in Denmark of other pathogens such as Coxiella burnetii and Chlamydophila abortus cannot be excluded. Due to the high prevalence of zoonotic microorganisms, precautions must be taken in handling abortions or assisting lambing, especially for pregnant women.

Development and evaluation of a palliative care curriculum for cystic fibrosis healthcare providers.

BACKGROUND: Primary palliative care refers to basic skills that all healthcare providers can employ to improve quality of life for patients at any stage of disease. Training in these core skills is not commonly provided to clinicians caring for cystic fibrosis (CF) patients. The objective of this study was to assess change in comfort with core skills among care team members after participation in CF-specific palliative care training focused on management of burdensome symptoms and difficult conversations. METHODS: A qualitative needs assessment was performed to inform the development of an 18-hour curriculum tailored to the chronicity and complexity of CF care. A 32-question pre- and post-course survey assessed CF provider comfort with the targeted palliative care skills in 5 domains using a 5-point Likert scale (1=very uncomfortable, 3=neutral, 5=very comfortable). RESULTS: Among course participants (n=16), mean overall comfort score increased by 0.9, from 3 (neutral) to 3.9 (comfortable) (p<0.001). Mean comfort level increased significantly (range 0.8 to 1.4) in each skill domain: use of supportive care resources, pain management, non-pain symptom management, communication, and psychosocial skills. CONCLUSIONS: CF-specific palliative care training was well received by participants and significantly improved self-assessed comfort with core skills.

The host-parasite relationship in bovine neosporosis.

Infection with the protozoan parasite Neospora caninum is thought to be a major cause of reproductive failure in cattle worldwide. Cattle infected with the parasite are three to seven times more likely to abort compared to uninfected cattle. The parasite may be transmitted to cattle through the ingestion of oocysts that are shed in the faeces of acutely infected dogs (definitive host of N. caninum) or by congenital infection from mother to foetus via the placenta. Interestingly, transplacental transmission can occur over consecutive pregnancies and congenitally infected heifers can transmit the parasite to their own offspring. This repeated vertical transmission observed in naturally infected cattle suggests that cattle do not easily develop effective immunity to the parasite, presenting a significant challenge to the development of a control strategy based on vaccination. Neosporosis is a disease of pregnancy and studying the bovine maternal and foetal immune responses during pregnancy will help us to understand the change in the balance between the parasite and the host that may result in disease of the foetus. Studies in non-pregnant cattle and in murine models of infection have shown the importance of T-helper 1-type immune responses involving pro-inflammatory cytokines, such as IFNgamma and IL-12, in limiting intracellular multiplication of the parasite. During pregnancy, changes occur in the immune system allowing the mother to accept the foetal allograft. Research in other species has stressed the crucial role of T-helper 2-type cytokines at the materno-foetal interface in maintaining the pregnancy and regulating the potentially damaging effect of Th-1 responses. Studies in cattle have shown that cell proliferation and IFNgamma responses may be significantly down-regulated around mid-gestation. This may mean that cattle are less able to cope with N. caninum infection at this time and are more likely to transmit the parasite to the foetus. Another important factor is the gestational age and hence immuno-competence of the foetus at the time of infection. Early in gestation, N. caninum infection of the placenta and subsequently the foetus usually proves fatal, whereas infection occurring in mid to late pregnancy may result in the birth of a congenitally infected but otherwise healthy calf. Studies of foetal immune responses have shown that at 14 weeks of gestation, lymphocytes only respond to mitogen, while by 24 weeks (mid-gestation), they respond to antigen by proliferating and releasing IFNgamma. Clearly, there are several factors influencing the outcome of N. caninum infection in pregnancy: the timing, quantity and duration of parasitaemia, the effectiveness of the maternal immune response and the ability of the foetus to mount an immune response against the parasite. The challenge is to design a vaccine that will prevent foetal infection by N. caninum. This is likely to involve a fine balancing act with the immune system that will allow intervention in a manner that will tip the host-parasite balance in favour of the host without compromising the pregnancy.

The comparative pathogenesis of neosporosis.

Since its first description in dogs in 1984, the protozoan parasite Neospora caninum has been found to infect a wide range of animals, worldwide. In cattle, N. caninum has particular significance as a cause of abortion in which persistence of infection in the mother, recrudescence of the parasite during pregnancy, and the vulnerability of the placenta and foetus to invasion are important features. This article discusses how Neospora invades cells, how it infects and causes disease in several animal species, and particularly how it has evolved a special niche in cattle and dogs that ensures its survival.

Immunisation of mice against neosporosis.

In the present study a murine encephalitis model was used to investigate if protection against neosporosis could be achieved by immunisation. Groups of 10 mice were immunised with a sublethal dose of live Neospora caninum tachyzoites, N. caninum antigens incorporated into iscoms, N. caninum lysate mixed with Quil A, or N. caninum lysate in PBS. Control mice were given Quil A only. Challenge infection with 2.5x10(6) N. caninum tachyzoites resulted in clinical symptoms that remained until the end of the experiment in the controls. In contrast, mice immunised with live parasites or parasite lysate in Quil A only showed mild and transient symptoms. Of nine mice immunised with N. caninum iscoms, seven recovered while two died. Most severely affected were the mice immunised with parasite lysate only; all of them died within 28 days post-infection. Histological examination and scoring of brain lesions gave a significantly lower (P<0.0001) lesion score in mice immunised with live parasites than in controls. The groups immunised with iscoms or lysate and Quil A also had reduced lesion scores (P<0.04 and 0.07, respectively) but not the group given parasite lysate alone. The lesions seen in the latter group differed from those in the other groups. There was less cellular reaction and more tachyzoites indicating an active infection. The N. caninum specific antibody responses and cytokine production (IFN-gamma, IL-4 and IL-5) of splenocytes were analysed at the time of challenge infection. The results suggest a correlation between protection and high levels of IFN-gamma. Also, the immune responses recorded in mice immunised with parasite lysate without adjuvant were relatively weak and more towards the Th2 type, when compared with the other immunisation schedules. This is consistent with the weaker inflammatory response observed in the brains of these mice.

Cytokine expression in the placenta of pregnant cattle after inoculation with Neospora caninum.

Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogenesis is not completely understood. Immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to the adverse effects of exacerbated Th1 type response at the maternal-foetal interface. Different clinical outcomes are known to occur following experimental infections of cattle at different stages of gestation, with foetal death being the most common finding during early gestation, and the birth of live congenitally infected calves following infection later in gestation. The aim of the current study was to characterize the cytokine expression in the placenta of cattle experimentally challenged with tachyzoites of the Nc-1 strain during early, mid and late gestation. Moderate to severe infiltration of IL-12, IFN-γ and TNF-α expressing cells was observed in the placentas collected at early gestation and this infiltration was more pronounced in the samples collected from challenged dams carrying non-viable foetuses, compared with the mothers carrying viable foetuses. In contrast, the infiltration of Th1 cytokine expressing-cells was mild following N. caninum infection in mid gestation and scarce during infection in late gestation. Scarce expression of IL-4 was observed in the placentas from N. caninum-challenged and negative control animals throughout gestation. The milder Th1 immune response observed during later stages of gestation following Nc-1 infection could partially explain the less severe clinical outcome when compared to early pregnancy.