Hospital-in-the-Home experience of first 23 COVID-19 patients at a regional NSW hospital.

Ambulatory care is an important service for patients with the COVID-19 infection especially in a regional area where most of the patients underwent home isolation. Escalation of treatment and timely transition to inpatient care are critical when COVID-19 patients deteriorate. Equally important is ensuring transfer into facility is carried out in a well-planned, safe manner to prevent exposure to health care professionals as well as other inpatients. This study is a summary of our COVID Hospital-in-the-Home (HITH) service and clinical presentation of COVID-19 patients.

Smoking in the family is most predictive of the development of childhood asthma in preterm babies <30 weeks gestation: Results of the Respiratory Outcomes Study 2 (RESPOS2).

OBJECTIVES: The Respiratory Outcomes Study 2 (RESPOS2) investigated the relationship between neonatal outcomes (specifically, chronic lung disease [CLD]) and environmental factors on the development of asthma and atopic outcomes at primary school age for preterm babies (PBs) <30 weeks gestational age (GA). METHODS: The study included all surviving PBs <30 weeks GA admitted to the Neonatal Intensive Care Unit at Canberra Hospital, Australian Capital Territory between 2007 and 2009. Parents were sent a questionnaire regarding asthma and atopy symptoms when the PBs were aged 5-7 years old. Data were compared based on CLD status. RESULTS: There were 103 PBs included in the study with a 68.9% response rate to the respiratory questionnaire (71/103). Of these PBs, 15/71 (21.1%) received a diagnosis of CLD. There were no significant differences with regards to asthma, hay fever or eczema in PBs either with or without CLD. The most significant predictor for the development of asthma was smoking in the family (Odds Ratio [OR]: 11.66, 95% Confidence Interval [CI]: 2.01-67.56) with a trend toward significance for family history of asthma (OR: 3.83, 95% CI: 0.85-17.25). CONCLUSION: The RESPOS2 has confirmed previous reports that CLD in PBs <30 weeks GA is not associated with the development of childhood asthma, hay fever or eczema. In our group of PBs, the strongest predictor of the development of asthma was smoking in the family.

The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration.

PURPOSE: Frailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the probe drug gentamicin. METHODS: Gentamicin concentrations and clinical data including the Reported Edmonton Frail Scale score were pooled from two prospective observational inpatient studies, one on prophylactic gentamicin for urologic surgery and one on therapeutic gentamicin for the empiric treatment of sepsis. Population pharmacokinetic modeling was performed using non-linear mixed effects modeling (NONMEM program) to determine the impact of frailty on gentamicin clearance. RESULTS: A one-compartment linear pharmacokinetic model best described the data and the addition of frailty to the model reduced the random variability in gentamicin clearance by 12 % after adjustment for renal function (estimated creatinine clearance using lean body weight) and lean body weight. Frail patients had an approximately 12 % lower (bootstrapping results: 14 % median) gentamicin clearance than non-frail patients (calculated as a fractional effect of frailty). CONCLUSIONS: Frailty may independently predict reduced clearance of gentamicin in older patients. Frailty could be considered in the development of dosing guidelines for drugs that undergo significant excretion through glomerular filtration.

Selective incivility: immigrant groups experience subtle workplace discrimination at different rates.

Immigrants play an increasingly important role in local labor markets. Not only do they grow steadily in number but also in cultural, educational, and skill diversity, underlining the necessity to distinguish between immigrant groups when studying discrimination against immigrants. We examined immigrant employees' subtle discrimination experiences in a representative sample in Switzerland, controlling for dispositional influences. Results showed that mainly members of highly competitive immigrant groups, from immediate neighbor countries, experienced workplace incivility and that these incivility experiences were related to higher likelihoods of perceived discrimination at work. This research confirms recent accounts that successful but disliked groups are particularly likely to experience subtle interpersonal discrimination.

Quantifying Physical Thrombus Characteristics on Cardiovascular Biomaterials Using MicroCT.

Hemocompatibility is a critical consideration when designing cardiovascular devices. Methods of assessing hemocompatibility range from in vitro protein adsorption and static platelet attachment to in vivo implantation. A standard preclinical assessment of biomaterial hemocompatibility is ex vivo quantification of thrombosis in a chronic arteriovenous shunt. This technique utilizes flowing blood and quantifies platelet accumulation and fibrin deposition. However, the physical parameters of the thrombus have remained unknown. This study presents the development of a novel method to quantify the 3D physical properties of the thrombus on different biomaterials: expanded polytetrafluoroethylene and a preclinical hydrogel, poly(vinyl alcohol). Tubes of 4-5 mm inner diameter were exposed to non-anticoagulated blood flow for 1 hour and fixed. Due to differences in biomaterial water absorption properties, unique methods, requiring either the thrombus or the lumen to be radiopaque, were developed to quantify average thrombus volume within a graft. The samples were imaged using X-ray microcomputed tomography (microCT). The methodologies were strongly and significantly correlated to caliper-measured graft dimensions (R2 = 0.994, p < 0.0001). The physical characteristics of the thrombi were well correlated to platelet and fibrin deposition. MicroCT scanning and advanced image analyses were successfully applied to quantitatively measure 3D physical parameters of thrombi on cardiovascular biomaterials under flow.

The clinical sensitivity of a single SARS-CoV-2 upper respiratory tract RT-PCR test for diagnosing COVID-19 using convalescent antibody as a comparator.

The clinical false negative rate of reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on a single upper respiratory tract sample was calculated using convalescent antibody testing as a comparator. The sensitivity in symptomatic individuals was 86.2% (25/29). Of the missed cases, one (3.5%) was detected by repeat RT-PCR, one by CT thorax and two (7.1%) by convalescent antibody. The clinical false negative rate of a single RT-PCR on an upper respiratory tract sample of 14% in symptomatic patients is reassuring when compared to early reports. This report supports a strategy of combining repeat swabbing, use of acute and convalescent antibody testing and CT thorax for COVID-19 diagnosis.

The immunobiology of avian systemic salmonellosis.

Avian systemic salmonellosis is primarily caused by Salmonella enterica serovar Gallinarum and serovar Pullorum causing the diseases Fowl Typhoid and Pullorum Disease respectively. During infection interaction with the immune system occurs in three main phases. First is invasion via the gastrointestinal tract. Infection with S. Pullorum or S. Gallinarum does not cause substantial inflammation, unlike S. Typhimurium or S. Enteritidis. Through in vitro models it was found that S. Gallinarum does not induce expression of CXC chemokines or pro-inflammatory cytokines such as IL-1beta or IL-6, whilst in an in vivo model S. Pullorum infection leads to down-regulation of CXCLi1 and CXCLi2 in the ileum. The absence of flagella in S. Gallinarum and S. Pullorum means they are not recognised by TLR5, which is believed to play a key role in the initiation of inflammatory responses, though other pathogen-factors are likely to be involved. The second phase is establishing systemic infection. Salmonella invade macrophages and probably dendritic cells and are translocated to the spleen and liver, where replication occurs. Salmonella survival is dependent on the Salmonella pathogenicity island 2 type III secretion system, which inhibits antimicrobial activity by preventing fusion of lysosymes with the phagocytic vacuole and by modulation of MHC and cytokine expression. Studies in resistant and susceptible chicken lines have shown that the interaction with macrophages is central to the progression of infection or immunological clearance. Primary macrophages from resistant animals are more efficient in killing Salmonella through respiratory burst and by induction of cytokine expression including the initiation of protective Th1 responses that leads to the third phase. Where replication of Salmonella is not controlled the death of the animal usually results. If the innate immune system is not able to control replication then cellular and humoral responses, primarily mediated through Th1-associated cytokines, are able to clear infection. In S. Pullorum a significant number of animals develop persistent infection of splenic macrophages. Here we show preliminary evidence of modulation of adaptive immunity away from a Th1 response to facilitate the development of the carrier state. In carrier animals persistence may lead to reproductive tract and egg infection associated with a decline in CD4+ T cell numbers and function associated with the onset of sexual maturity in hens.

A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer.

PURPOSE: The primary aim of this study was to measure the objective tumor response rate following treatment with indisulam [E7070; N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] as second-line therapy in patients with advanced non-small cell lung cancer. The secondary aims were to determine progression-free survival, to assess the safety and tolerability of indisulam, and to study its pharmacokinetic and pharmacodynamic profile. EXPERIMENTAL DESIGN: Patients were randomized to receive indisulam every 3 weeks either as a single i.v. dose of 700 mg/m(2) on day one (dx1) or 130 mg/m(2) given on days 1 to 5 inclusive as a daily infusion (dx5). All patients had previously received platinum-based chemotherapy. RESULTS: Forty-four patients were randomized. Only minor responses were seen. Myelosuppression, gastrointestinal symptoms, and lethargy were the most common toxicities and were more frequent in the dx1 arm. The pharmacokinetics of indisulam in each treatment schedule were adequately described using a previously developed population pharmacokinetic model and were mostly consistent with the results of the phase I program. Flow cytometric analysis of endobronchial and metastatic disease revealed a reduction in the fraction of cycling cells and an increase in apoptosis following indisulam compared with pretreatment levels. CONCLUSIONS: We conclude that, despite evidence of tumor-specific indisulam-induced apoptosis, neither of these treatment schedules has single-agent activity as second-line treatment of non-small cell lung cancer.

Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study): study protocol for a cluster randomised controlled trial.

BACKGROUND: People with severe mental illnesses die up to 20 years earlier than the general population, with cardiovascular disease being the leading cause of death. National guidelines recommend that the physical care of people with severe mental illnesses should be the responsibility of primary care; however, little is known about effective interventions to lower cardiovascular disease risk in this population and setting. Following extensive peer review, funding was secured from the United Kingdom National Institute for Health Research (NIHR) to deliver the proposed study. The aim of the trial is to test the effectiveness of a behavioural intervention to lower cardiovascular disease risk in people with severe mental illnesses in United Kingdom General Practices. METHODS/DESIGN: The study is a cluster randomised controlled trial in 70 GP practices for people with severe mental illnesses, aged 30 to 75 years old, with elevated cardiovascular disease risk factors. The trial will compare the effectiveness of a behavioural intervention designed to lower cardiovascular disease risk and delivered by a practice nurse or healthcare assistant, with standard care offered in General Practice. A total of 350 people will be recruited and followed up at 6 and 12 months. The primary outcome is total cholesterol level at the 12-month follow-up and secondary outcomes include blood pressure, body mass index, waist circumference, smoking status, quality of life, adherence to treatments and services and behavioural measures for diet, physical activity and alcohol use. An economic evaluation will be carried out to determine the cost effectiveness of the intervention compared with standard care. DISCUSSION: The results of this pragmatic trial will provide evidence on the clinical and cost effectiveness of the intervention on lowering total cholesterol and addressing multiple cardiovascular disease risk factors in people with severe mental illnesses in GP Practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13762819. Date of Registration: 25 February 2013. Date and Version Number: 27 August 2014 Version 5.

Immunological changes at point-of-lay increase susceptibility to Salmonella enterica Serovar enteritidis infection in vaccinated chickens.

Chicken eggs are the main source of human Salmonella enterica serovar Enteritidis infection. S. Enteritidis infects the oviduct and ovary of the chicken leading to infection of developing eggs. Therefore, control in poultry production is a major public health priority. Vaccination of hens has proved successful in control strategies in United Kingdom leading to a 70% drop in human cases since introduced. However, as hens reach sexual maturity they become immunosuppressed and it has been postulated this leads to increased susceptibility to Salmonella infection. In this study we define the changes to the systemic and reproductive tract-associated immune system of hens throughout sexual development by flow cytometry and histology and determine changes in susceptibility to experimental S. Enteritidis challenge in naive and vaccinated hens. Changes to both systemic and local immune systems occur in chickens at sexual development around 140 days of age. The population of several leukocyte classes drop, with the greatest fall in CD4+ lymphocyte numbers. Within the developing reproductive tract there an organised structure of lymphocytic aggregates with γδ-T lymphocytes associated with the mucosa. At point-of-lay, this organised structure disappears and only scattered lymphocytes remain. Protection against Salmonella challenge is significantly reduced in vaccinated birds at point-of-lay, coinciding with the drop in CD4+ lymphocytes. Susceptibility to reproductive tract infection by Salmonella increased in vaccinated and naïve animals at 140 and 148 days of age. We hypothesise that the drop in γδ-T lymphocytes in the tract leads to decreased innate protection of the mucosa to infection. These findings indicate that systemic and local changes to the immune system increase the susceptibility of hens to S. Enteritidis infection. The loss of protective immunity in vaccinated birds demonstrates that Salmonella control should not rely on vaccination alone, but as part of an integrated control strategy including biosecurity and improved animal welfare.

Practical guidance: the use of social media in oncology practice.

The penetration of social media into modern society has become a worldwide cultural phenomenon. Social media use widely accessible Web-based and mobile technologies to facilitate the creation and sharing of user-generated content in a collaborative and social manner. The uptake of social media in medicine provides new opportunities for health care professionals and institutions to interact with patients and other professionals. Oncologists may use social media as a platform for patient education and authoritative health messaging, for professional development and knowledge sharing, and for direct patient interaction, although this may be fraught with important legal and privacy concerns. In this article, a working group of the ASCO Integrated Media and Technology Committee explores how oncologists might responsibly use social media in their professional lives. Existing social media policies from hospitals, health systems, and pharmaceutical industries are examined to identify common concepts informing the development of future guidelines. Key principles identified include establishing institutional ownership of social media activities and safeguarding protected health information. Furthermore, oncologists must not confuse the roles of provider of information and provider of care, must understand regulations related to state licensure and medical records, and must recognize the importance of transparency and disclosure of potential conflicts of interest. social media may be particularly useful for raising the awareness of and recruitment to clinical trials, but compliance with federal and state regulations and areas under the purview of a local institutional review board must also be ensured. Examples of constructive use of social media in oncology with Facebook, Twitter, and YouTube are provided.

Watchdog.

Qlf a Registered General Nurse/ State Registered Nurse (RGN/ SRN) is employed in a factory as an occupational health nurse but has neither obtained nor enrolled for a course leading to an Occupational Health Nursing Certificate (OHNC), is this within the Professional Code of Conduct and what are the consequences should a fatality occur in the work place?