Enhancing the local workforce outcomes for rural LICs: what is the role of the local health service in leading innovation in medical education?

Introduction: It is now 25 years since the Riverland health service began its partnership with Flinders University to create the Parallel Rural Community Curriculum (PRCC) in rural South Australia. What started as a workforce program quickly became a successful disruptive technology for broader pedagogy in medical education. Despite more graduates of the PRCC choosing rural practice compared with their urban rotation-based colleagues, local medical workforce crises have persisted.

Triple quadrupole LC/MS method for the simultaneous quantitative measurement of cefiderocol and meropenem in serum.

: therapeutic drug monitoring is a crucial aspect of the management of hospitalized patients. The correct dosage of antibiotics is imperative to ensure their adequate exposure specially in critically ill patients. The aim of this study is to establish and validate a robust and fast liquid chromatography-tandem mass spectrometry (LC/MS) method for the simultaneous quantification of two important antibiotics in critically ill patients, cefiderocol and meropenem in human plasma.

Seropositivity and geographical distribution of Strongyloides stercoralis in Australia: A study of pathology laboratory data from 2012-2016.

Background: There are no national prevalence studies of Strongyloides stercoralis infection in Australia, although it is known to be endemic in northern Australia and is reported in high risk groups such as immigrants and returned travellers. We aimed to determine the seropositivity (number positive per 100,000 of population and percent positive of those tested) and geographical distribution of S. stercoralis by using data from pathology laboratories.

Process intensification of anaerobic digestion: Influence on mixing and process performance.

The adoption of process intensification to anaerobic digestion can present significant complications for digester mixing and process performance. This work investigated how increasing the solids concentration of the digester sludge influenced the process at various mixing energy inputs. Based on the results, adequate mixing is defined qualitatively as the input of sufficient energy to mobilize the reactor contents without producing significant regions of inhibitory shear force.

Quantitative investigation of hydraulic mixing energy input during batch mode anaerobic digestion and its impact on performance.

The relationship between mixing energy input and biogas production was investigated by anaerobically digesting sewage sludge in lab scale, hydraulically mixed, batch mode digesters at six different specific energy inputs. The goal was to identify how mixing energy influenced digestion performance at quantitative levels to help explain the varying results in other published works. The results showed that digester homogeneity was largely uninfluenced by energy input, whereas cumulative biogas production and solids destruction were.

Utilization of community health workers in Canada's Children's Oral Health Initiative for indigenous communities.

Objective: The Children's Oral Health Initiative (COHI) is a federally funded community-based preventive dental programme implemented in geographically remote Canadian Indigenous communities. The study investigated the effect of the availability of local community health workers (COHI Aides) on access to the programme's preventive dental services for children.

Methods: Twenty-five communities were continuously enrolled in the COHI during the 7-year study period.

The perceptions of first nation participants in a community oral health initiative.

The Children's Oral Health Initiative (COHI) is a federally funded community-based preventive dental program for children and their caregivers living in geographically isolated Canadian Aboriginal communities. The goal of the program is to improve access to preventive dental services for children of 0-7 years of age. It utilises community health workers in collaboration with dental therapists to promote and deliver the program.

Combining Slaughterhouse Surveillance Data with Cattle Tracing Scheme and Environmental Data to Quantify Environmental Risk Factors for Liver Fluke in Cattle.

Liver fluke infection causes serious disease (fasciolosis) in cattle and sheep in many regions of the world, resulting in production losses and additional economic consequences due to condemnation of the liver at slaughter. Liver fluke depends on mud snails as an intermediate host and infect livestock when ingested through grazing. Therefore, environmental factors play important roles in infection risk and climate change is likely to modify this.

Perspective: 4β-hydroxycholesterol as an emerging endogenous biomarker of hepatic CYP3A.

A key goal in the clinical development of a new molecular entity is to quickly identify whether it has the potential for drug-drug interactions. In particular, confirmation of in vitro data in the early stage of clinical development would facilitate the decision making and inform future clinical pharmacology study designs. Plasma 4β-hydroxycholesterol (4β-HC) is considered as an emerging endogenous biomarker for cytochrome P450 3A (CYP3A), one of the major drug metabolizing enzymes.

The Children's Oral Health Initiative: An intervention to address the challenges of dental caries in early childhood in Canada's First Nation and Inuit communities.

Objective: The objective of the Children's Oral Health Initiative (COHI) is to increase access to preventive oral health services provided to First Nations and Inuit (FN/I) children living on federal reserves and in remote communities.

Participants: COHI targets preschool children; 5-7-year-olds; pregnant women; and parents/caregivers in FN/I communities.

Setting: The program was piloted in 2004 by Health Canada and is potentially available to all FN/I communities.

Recommendations on the Development of a Bioanalytical Assay for 4β-Hydroxycholesterol, an Emerging Endogenous Biomarker of CYP3A Activity.

The availability of reliable assays for measuring 4β-hydroxycholesterol (4β-HC), a CYP3A metabolite of cholesterol, is an important step in qualifying this endogenous moiety as a biomarker of CYP3A activity. Liquid and gas chromatographic methods with mass spectrometric detection have been developed with varying sensitivities, with or without derivatization. Care must be taken to chromatographically resolve 4β-HC from the multiple isobaric cholesterol oxidation products present in plasma, including 4α-hydroxycholesterol (4α-HC).

Migration and multiple sclerosis in immigrants from United Kingdom and Ireland to Australia: a reassessment. III: risk of multiple sclerosis in UKI immigrants and Australian-born in Hobart, Tasmania.

Our previous work suggested that migrants from the United Kingdom and Ireland (UKI) to Australia who left their home country at a young age had a longer interval between immigration and onset and likely acquired MS in Australia. In the present study, we reassessed Australian-born cases of MS identified in Hobart, Tasmania, a relatively high-risk zone, in our 1981 survey and compared these with cases of MS in UKI immigrants incident in Australia. The incidence of MS in Australian-born residents rose from 1.

The use of laboratory scale reactors to predict sensitivity to changes in operating conditions for full-scale anaerobic digestion treating municipal sewage sludge.

Anaerobic digestion of sewage sludge is highly complex and prone to inhibition, which can cause major issues for digester operators. The result is that there have been numerous investigations into changes in operational conditions, however to date all have focused on the qualitative sensitivities, neglecting the quantitative. This study therefore aimed to determine the quantitative sensitivities by using factorial design of experiments and small semi continuous reactors.

Two studies on reversal of opioid-induced respiratory depression by BK-channel blocker GAL021 in human volunteers.

Background: Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced respiratory depression in animals due to a stimulatory effect on ventilation at the carotid bodies. To assess in humans whether GAL021 stimulates breathing in established opioid-induced respiratory depression and to evaluate its safety, a proof-of-concept double-blind randomized controlled crossover study on isohypercapnic ventilation (study 1) and subsequent double-blind exploratory study on poikilocapnic ventilation and nonrespiratory end points (study 2) was performed.

Respiratory stimulant drugs in the post-operative setting.

Drug-induced respiratory depression (DIRD) is a common problem encountered post-operatively and can persist for days after surgery. It is not always possible to predict the timing or severity of DIRD due to the number of contributing factors. A safe and effective respiratory stimulant could improve patient care by avoiding the use of reversal agents (e.

PhRMA survey on the conduct of first-in-human clinical trials under exploratory investigational new drug applications.

The FDA guidance on exploratory IND studies is intended to enable sponsors to move ahead more efficiently with the development of promising candidates. A survey of PhRMA member companies was conducted in 2007 to obtain a cross-sectional industry perspective on the current and future utility of exploratory IND studies. About 56% of survey responders (9 companies of 16 survey responders) conducted or were planning to conduct clinical studies under exploratory INDs.

Pharmacokinetics of a single dose of the antifungal posaconazole as oral suspension in subjects with hepatic impairment.

Objective: To evaluate posaconazole pharmacokinetics in subjects with different degrees of hepatic impairment compared with matched healthy subjects.

Research Design And Methods: A total of 37 subjects were enrolled in this open-label, single-dose, parallel-group study; 19 with hepatic impairment and 18 healthy subjects with matching demographics. Each subject received a single 400-mg oral dose of posaconazole after a high-fat meal.

Individual personality and the spatial distribution of groups of grazing animals: an example with sheep.

Impacts of individual personality on group distribution were investigated using sheep (Ovis aries) as a model. In an indoor exploration test, individuals who visited <4 (out of 6) objects in a novel environment were classified as 'shy' (n=10), and those who visited 5 or 6 objects were classified as 'bold' (n=10). Nine weeks later, using a series of groups (n=40) of either 5 shy or 5 bold sheep, we measured distribution at pasture and responses to disturbance and the approach of a human handler.

Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers.

Background: Like itraconazole and ketoconazole, posaconazole, a broad-spectrum oral triazole antifungal, inhibits the activity of the cytochrome P450 (CYP) isozyme 3A4. Midazolam, a short-acting benzodiazepine, is metabolized by CYP3A4. Potential drug interactions can be expected in patients who are concurrently receiving inhibitors and substrates of CYP3A4 (eg, ketoconazole, posaconazole) and benzodiazepines (eg, midazolam).

Effects of oral posaconazole on the pharmacokinetics of sirolimus.

Objectives: Azole antifungal agents are often coadministered with immunosuppressants to recipients of solid organ and hematopoietic stem cell transplants. Posaconazole, an extended-spectrum triazole, is an inhibitor of the cytochrome P450 (CYP) isoenzyme CYP3A4, and sirolimus, an immunosuppressant, is a substrate of the enzyme. We evaluated the effects of posaconazole on sirolimus pharmacokinetics in an open-label, multiperiod, drug-interaction study.

Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers.

A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost).

Community-acquired methicillin-resistant Staphylococcus aureus in Central Australia.

To date, there has been scant information about the burden of methicillin-resistant Staphylococcus aureus infections in Central Australia. Our aims were to determine the proportion of Staphylococcus aureus infections due to methicillin-resistant strains in Central Australia, to characterise resistance to non-beta lactam antibiotics and to correlate findings with available demographic information. We retrospectively reviewed S.

Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient.

Ciliary neurotrophic factor (CNTF) receptor controls a pathway supporting the differentiation and survival of a wide range of neural cell types during development and in adulthood. Cardiotrophin-like cytokine (CLC)-cytokine-like factor 1 (CLF) composite cytokine is a second ligand for the CNTF alpha-component receptor (CNTFRalpha). This composite cytokine is built on the structural model of IL-12, with a complex formed by a four-helix bundle type I cytokine, CLC (also referred to as CLCF1), bound to a soluble receptor subunit, CLF (also known as CRLF1).

Effect of a selective CYP2C9 inhibitor on the pharmacokinetics of nateglinide in healthy subjects.

Purpose: The objective of the study was to determine the effect of a potent and selective CYP2C9 inhibitor, sulfinpyrazone (Anturane), on the pharmacokinetics of nateglinide (Starlix), a novel antidiabetic drug which is primarily (approximately 70%) metabolized via CYP2C9.

Methods: This was a randomized, open-label, two-period, crossover study in 18 healthy volunteers. Nateglinide was administered as a single 120-mg oral dose alone (reference) on day 1 or in combination with sulfinpyrazone (test) on day 7, following twice-daily 200-mg oral doses (i.