Bulls fed a high-gain diet decrease blastocyst formation after in vitro fertilization.

In brief: Paternal high-gain diet reduces blastocyst development following in vitro fertilization and embryo culture but does not affect gene expression or cellular allocation of resultant blastocysts. Abstract: Bulls used in cattle production are often overfed to induce rapid growth, early puberty, and increase sale price. While the negative consequences of undernutrition on bull sperm quality are known, it is unclear how a high-gain diet influences embryo development. We hypothesized that semen collected from bulls fed a high-gain diet would have a reduced capacity to produce blastocysts following in vitro fertilization. Eight mature bulls were stratified by body weight and fed the same diet for 67 days at either a maintenance level (0.5% body weight per day; n = 4) or a high-gain rate (1.25% body weight per day; n = 4). Semen was collected by electroejaculation at the end of the feeding regimen and subjected to sperm analysis, frozen, and used for in vitro fertilization. The high-gain diet increased body weight, average daily gain, and subcutaneous fat thickness compared to the maintenance diet. Sperm of high-gain bulls tended to have increased early necrosis and had increased post-thaw acrosome damage compared with maintenance bulls, but diet did not affect sperm motility or morphology. Semen of high-gain bulls reduced the percentage of cleaved oocytes that developed to blastocyst stage embryos. Paternal diet had no effect on the number of total or CDX2-positive cells of blastocysts, or blastocysts gene expression for markers associated with developmental capacity. Feeding bulls a high-gain diet did not affect sperm morphology or motility, but increased adiposity and reduced the ability of sperm to generate blastocyst-stage embryos.

Under or over? General practitioner charging of Medicare.

BACKGROUND AND OBJECTIVES: In 2022, media reports alleged that doctors, particularly general practitioners (GPs), are defrauding Medicare, claiming $8 billion lost through fraud/non-compliance. This study examined Medicare Benefits Schedule billing patterns by consultation length to estimate overcharging or undercharging by GPs, and the cost/savings to Medicare. METHOD: A subset of data from the Bettering the Evaluation And Care of Health (BEACH) program from 2013 to 2016, which included length of consultation information, was analysed. RESULTS: Of 89,765 consultations, GPs undercharged 11.8% of consultations and overcharged 1.6%. Of the 2760 GPs sampled, 816 (29.6%) overcharged at least once and 2334 (84.6%) undercharged at least once. Of the GPs who overcharged at least once, 85.4% also undercharged. The total effect of GP undercharging and overcharging was a net saving of $351.7 million to Medicare. DISCUSSION: This study shows that GPs undercharging and overcharging saved Medicare over one-third of a billion dollars in 2021-22. The findings of this study do not support the media claims of widespread fraud by GPs.

Developing self-report disability questions for a voluntary patient registration form for general practice in Australia.

OBJECTIVE: This article reports on research undertaken to develop self-report disability questions for a patient registration form that may be implemented in general practices across Australia as part of a voluntary patient registration program. METHODS: There were four research components: rapid review of approaches for capturing disability information; expert informant interviews (n=19); stakeholder consultation via virtual focus groups (n=65); and online survey (n=35). Findings from each component informed development of materials for subsequent components in an iterative research process. RESULTS: Three disability questions were developed: two alternative questions for identifying disability, conceptually aligned with the operational definition of disability in Australia's national disability survey; one question to determine the patient's disability group/s. CONCLUSIONS: Knowledge and perspectives from a variety of sources informed the development of self-report questions to identify patients with disability. Implementing these questions represents an opportunity to test new ways of capturing disability information suited to mainstream service provision contexts. It will be essential to evaluate the quality of the data produced during the initial period of implementation. IMPLICATIONS FOR PUBLIC HEALTH: The collection of self-report patient disability information within general practice, using standard and conceptually-sound questions, has the potential to support improved provision of health care to patients with disability.

A call to action for more disability-inclusive health policy and systems research.

To date, the exclusion of people with disability participating in research has limited the evidence base informing health system strengthening policy and practice more generally, and addressing disability-related inequalities in access to health services and better health outcomes more particularly. Given that more than 1 billion people, or 16% of the world's population, have a disability, we may fail to respond to the needs of a large proportion of the population unless we are purposeful with inclusion. Our research in this area indicates that online qualitative methods can be effective in engaging under-represented groups and are essential to ensure their input into health policy and systems research. This has important implications for researchers whose responsibility it is to make all health research disability inclusive, for ethical and methodological reasons, so they do not perpetuate the under-representation of people with disability in health policy and systems research. Our paper puts forward several recommendations to facilitate more people with disability participating in health policy and systems research. By critically reflecting on a health system strengthening research project, in which we purposefully aimed to support the participation of people with disability, we identify lessons learnt and issues to consider when planning and conducting accessible research. We also propose a set of actions for moving the agenda forward.

Foot, ankle, and leg problems in Australian primary care: consultation patterns, management practices, and costs.

OBJECTIVE: To explore consultation patterns, management practices, and costs of foot, ankle, and leg problems in Australian primary care. STUDY DESIGN: We analyzed data from the Bettering the Evaluation and Care of Health program, April 2000 to March 2016. Foot, ankle, and leg problems were identified using the International Classification of Primary Care, Version 2 PLUS terminology. Data were summarized using descriptive statistics examining general practitioner (GP) and patient characteristics associated with a foot, ankle, or leg problem being managed. Cost to government was estimated by extracting fees for GP consultations, diagnostic imaging, and pathology services from the Medicare Benefits Schedule (MBS) database. Costs for prescription-only medicines were extracted from the Pharmaceutical Benefits Schedule and for nonprescribed medications, large banner discount pharmacy prices were used. RESULTS: GPs recorded 1,568,100 patient encounters, at which 50,877 foot, ankle, or leg problems were managed at a rate of 3.24 (95% confidence intervals [CIs] 3.21-3.28) per 100 encounters. The management rate of foot, ankle, or leg problems was higher for certain patient characteristics (older, having a health care card, socioeconomically disadvantaged, non-Indigenous, and being English speaking) and GP characteristics (male sex, older age, and Australian graduate). The most frequently used management practice was the use of medications. The average cost (Australian dollars) per encounter was A$52, with the total annual cost estimated at A$256m. CONCLUSIONS: Foot, ankle, and leg problems are frequently managed by GPs, and the costs associated with their management represent a substantial economic impact in Australian primary care.

Encounters and management of oral conditions at general medical practices in Australia.

BACKGROUND: Poor oral health has been widely recognised as an ongoing public health issue. Patients with oral conditions may visit either a general practitioner (GP) or a dental practitioner for management. The aims of this study are to report (i) the GP management rate of oral health conditions by patient and GP demographics, (ii) what specific oral conditions were managed, and (iii) how GPs managed oral conditions. METHODS: Data from the Bettering the Evaluation and Care of Health study (2006 to 2016 inclusive) were analysed. Descriptive statistics with 95% confidence intervals around point estimates were used to summarise data. Multivariate logistic regression was performed to determine the independent effect of patient and GP characteristics. RESULTS: A total of 972,100 GP encounters were included in the dataset, with oral condition-related encounters managed at a rate of 1.19 oral conditions per 100 GP encounters. Patients who were aged 54 years or younger, resided in a socioeconomically disadvantaged area, came from a non-English speaking background or Indigenous background were more likely to have oral conditions managed by GPs. The most commonly reported oral conditions were dental and oral mucosa-related. Over 60% of oral conditions were managed by GPs through prescribed medications. CONCLUSIONS: This study provided an overview of management of oral conditions by GPs in Australia. Patients from certain vulnerable demographic groups were more likely to attend a GP for management of oral conditions. Common oral conditions and management approaches were identified. The findings of this study contribute to public health and health policy discussions around optimising primary care provision in oral health.

Australian children's foot, ankle and leg problems in primary care: a secondary analysis of the Bettering the Evaluation and Care of Health (BEACH) data.

OBJECTIVES: To explore children's foot, ankle and leg consultation patterns and management practices in Australian primary care. DESIGN: Cross-sectional, retrospective study. SETTING: Australia Bettering the Evaluation and Care of Health program dataset. PARTICIPANTS: Data were extracted for general practitioners (GPs) and patients <18 years from April 2000 to March 2016 inclusive. MAIN OUTCOME MEASURES: Demographic characteristics: sex, GP age groups (ie, <45, 45-54, 55+ years), GP country of training, patient age grouping (0-4, 5-9, 10-14, 15-18 years), postcode, concession card status, indigenous status, up to three patient encounter reasons, up to four encounter problems/diagnoses and the clinical management actioned by the GP. RESULTS: Children's foot, ankle or leg problems were managed at a rate of 2.05 (95% CI 1.99 to 2.11) per 100 encounters during 229 137 GP encounters with children. There was a significant increase in the rate of foot, ankle and leg problems managed per 100 children in the population, from 6.1 (95% CI 5.3 to 6.8) in 2005-2006 to 9.0 (95% CI 7.9 to 10.1) in 2015-2016. Management of children's foot, ankle and leg problems were independently associated with male patients (30% more than female), older children (15-18 years were 7.1 times more than <1 years), male GPs (13% more) and younger GPs (<45 years of age 13% more than 55+). The top four most frequently managed problems were injuries (755.9 per 100 000 encounters), infections (458.2), dermatological conditions (299.4) and unspecified pain (176.3). The most frequently managed problems differed according to age grouping. CONCLUSIONS: Children commonly present to GPs for foot, ankle and leg problems. Presentation frequencies varied according to age. Unexpectedly, conditions presenting commonly in adults, but rarely in children, were also frequently recorded. This data highlights the importance of initiatives supporting contemporary primary care knowledge of diagnoses and management of paediatric lower limb problems to minimise childhood burden of disease.

Equine Platelet Lysate Gel: A Matrix for Mesenchymal Stem Cell Delivery.

A variety of bioscaffolds have been developed as carriers for the delivery of mesenchymal stem cells (MSCs), however, many of them are unable to provide direct cell nourishment, a critical factor for survival and retention of MSCs at the site of delivery. Platelet lysate is a plasma-derived product rich in growth factors that can be turned into a gel matrix following the addition of calcium chloride. Our objective was to characterize growth factor and cytokine release of equine platelet lysate gel (ePL gel) encapsulated with MSCs over time and to measure the viability and proliferation of ePL gel-encapsulated MSCs for up to 14 days. The release of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), transforming growth factor beta (TGF-ß), vascular endothelial growth factor (VEGF), and platelet-derived growth factor BB (PDGF-BB), as well as fibrinogen degradation, were measured from ePL gel with and without equine bone marrow-derived MSCs and compared with MSCs in monolayer. MSC proliferation and viability within the gel were assessed up to 14 days. Compared with monolayer MSC cultures, significantly higher concentrations of IL-1ß, IL-10, and TGF-ß were measured from supernatants collected from ePL gel containing MSCs at various time points. Significantly lower concentrations of PDGF-BB were measured in the supernatant when MSCs were incorporated in ePL gel while VEGF tended to be increased compared with MSCs in monolayer. Incorporation in ePL gel for up to 14 days did not appear to affect viability and proliferation rates of MSCs as these were found to be similar to those measured in monolayer cell culture. ePL gel may have the potential to serve as bioscaffold for MSC delivery since it appears to support the proliferation and viability of MSCs for up to 14 days.

Health Statistics in Australia: What We Know and Do Not Know.

Australia is a federation of six states and two territories (the States). These eight governmental entities share responsibility for health and health services with the Australian Government. Mortality statistics, including causes of death, have been collected since the late 19th century, with national data produced by the (now) Australian Bureau of Statistics (ABS) from 1907. Each State introduced hospital in-patient statistics, assisted by State offices of the ABS. Beginning in the 1970s, the ABS conducts regular health surveys, including specific collections on Aboriginal and Torres Strait Islander peoples. Overall, Australia now has a comprehensive array of health statistics, published regularly without political or commercial interference. Privacy and confidentiality are guaranteed by legislation. Data linkage has grown and become widespread. However, there are gaps, as papers in this issue demonstrate. Most notably, data on primary care patients and encounters reveal stark gaps. This paper accompanies a range of papers from expert authors across the health statistics spectrum in Australia. It is hoped that the collection of papers will inform interested readers and stand as a comprehensive review of the strengths and weaknesses of Australian health statistics in the early 2020s.

General Practice Statistics in Australia: Pushing a Round Peg into a Square Hole.

In Australia, general practice forms a core part of the health system, with general practitioners (GPs) having a gatekeeper role for patients to receive care from other health services. GPs manage the care of patients across their lifespan and have roles in preventive health care, chronic condition management, multimorbidity and population health. Most people in Australia see a GP once in any given year. Draft reforms have been released by the Australian Government that may change the model of general practice currently implemented in Australia. In order to quantify the impact and effectiveness of any implemented reforms in the future, reliable and valid data about general practice clinical activity over time, will be needed. In this context, this commentary outlines the historical and current approaches used to obtain general practice statistics in Australia and highlights the benefits and limitations of these approaches. The role of data generated from GP electronic health record extractions is discussed. A methodology to generate high quality statistics from Australian general practice in the future is presented.

Safety and efficacy of intravesical instillation of resiniferatoxin in healthy cats: A preliminary study.

Objectives: To evaluate the safety of intravesical application of resiniferatoxin (RTX) in healthy cats and its effects on calcitonin gene-related peptide (CGRP) and substance P (SP) produced by C-fibers. Methods: Seven adult female cats received either 25 mL of saline (control; n = 1), or intravesical RTX at 5, 25, or 50 µg in 25 mL of saline to a final concentration of 0.2 µg/mL (318 nM), 1 µg/mL (1,591 nM), and 2 µg/mL (3,181 nM) (n = 2 per group). The treatment was instilled into the urinary bladder for 20 min. Plasma concentrations of RTX were measured at 0, 0.5, 1, and 4 h. Physical exam, complete blood count, and serum biochemical analysis were performed on day 0, 7, and 14. After 14 days, the sacral dorsal root ganglia (DRG) and the urinary bladder were harvested for histological and immunofluorescence analysis. Results: Intravesical RTX was well tolerated and plasma concentrations were below the quantifiable limits except for one cat receiving 1 µg/mL. Mild to moderate histopathological changes, including epithelial changes, edema, and blood vessel proliferation, were observed at lower doses (0.2 and 1 µg/mL), and were more severe at the higher dose (2 µg/mL). C-fiber ablation was observed in the urinary bladder tissue at all doses, as shown by an apparent reduction of both CGRP and SP immunoreactive axons. Conclusion: A dose of 25 µg (1 µg/mL) of RTX instilled in the urinary bladder of healthy cats appeared to decrease the density of SP and CGRP nerve axons innervating bladder and induced moderate changes in the bladder tissue.

Antimicrobial Effects of Equine Platelet Lysate.

The development of antimicrobial resistant bacteria and the lack of novel antibiotic strategies to combat those bacteria is an ever-present problem in both veterinary and human medicine. The goal of this study is to evaluate platelet lysate (PL) as a biological alternative antimicrobial product. Platelet lysate is an acellular platelet-derived product rich in growth factors and cytokines that is manufactured via plateletpheresis and pooled from donor horses. In the current study, we sought to define the antimicrobial properties of PL on select gram-positive and gram-negative bacteria. Results from an end-point in vitro assay showed that PL did not support bacterial growth, and in fact significantly reduced bacterial content compared to normal growth media. An in vitro assay was then utilized to further determine the effects on bacterial growth dynamics and showed that all strains exhibited a slower growth rate and lower yield in the presence of PL. The specific effects of PL were unique for each bacterial strain: E. coli and P. aeruginosa growth was affected in a concentration-dependent manner, such that higher amounts of PL had a greater effect, while this was not true for S. aureus or E. faecalis. Furthermore, the onset of exponential growth was delayed for E. coli and P. aeruginosa in the presence of PL, which has significant clinical implications for developing a dosing schedule. In conclusion, our findings demonstrate the potential value of PL as a broad-spectrum antimicrobial that would offer an alternative to traditional antibiotics for the treatment of bacterial infection in equine species.

Pharmacokinetics and pharmacodynamics of methadone administered intravenously and intramuscularly to isoflurane-anesthetized chickens.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of methadone after IV or IM administration to isoflurane-anesthetized chickens. ANIMALS: 6 healthy adult Hy-Line hens. PROCEDURES: In a randomized crossover-design study, methadone (6 mg/kg) was administered IV and IM to isoflurane-anesthetized chickens with a 1-week washout period between experiments. Blood samples were collected immediately before and at predetermined time points up to 480 minutes after methadone administration. Plasma concentrations were determined by liquid chromatography-mass spectrometry, and appropriate compartmental models were fit to the plasma concentration-versus-time data. Cardiorespiratory variables were compared between treatments and over time with mixed-effect repeated-measures analysis. RESULTS: A 3-compartment model best described the changes in plasma methadone concentration after IV or IM administration. Estimated typical values for volumes of distribution were 692 mL/kg for the central compartment and 2,439 and 2,293 mL/kg for the first and second peripheral compartments, respectively, with metabolic clearance of 23.3 mL/kg/min and first and second distributional clearances of 556.4 and 51.8 mL/kg/min, respectively. Typical bioavailability after IM administration was 79%. Elimination half-life was 177 minutes, and maximum plasma concentration after IM administration was 950 ng/mL. Heart rate was mildly decreased at most time points beginning 5 minutes after IV or IM drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Disposition of methadone in isoflurane-anesthetized chickens was characterized by a large volume of distribution and moderate clearance, with high bioavailability after IM administration. Additional studies are warranted to assess pharmacokinetics and pharmacodynamics of methadone in awake chickens.

NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development.

The cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced notch signaling in all TECs resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a notch signal, consistent with notch signaling occurring in mTEC progenitors. These data provide strong evidence for a requirement for notch signaling in specification of the mTEC lineage.

What are chronic conditions that contribute to multimorbidity?

BACKGROUND: There is currently no accepted standard definition for chronic conditions. OBJECTIVE: The objective of this article is to provide an overview of the characteristics that define health conditions as chronic. DISCUSSION: A list of health conditions classified as chronic should be made available to all general practitioners and policymakers in Australia. This will assist in the claims process for chronic disease management and aid the selection of patients for healthcare home enrolment. Based on assessment of the usual duration, prognosis, sequelae and pattern of recurrence or deterioration, a defined list of chronic conditions classified according to the International Classification of Primary Care, version 2 (ICPC-2) is available for consideration.

Hox genes in the pharyngeal region: how Hoxa3 controls early embryonic development of the pharyngeal organs.

The pharyngeal organs, namely the thyroid, thymus, parathyroids, and ultimobranchial bodies, derive from the pharyngeal endoderm during embryonic development. The pharyngeal region is a segmented structure comprised of a series of reiterated structures: the pharyngeal arches on the exterior surface, the pharyngeal pouches on the interior, and a mesenchymal core. It is well known that Hox genes control spatial identity along the anterior-posterior axis of the developing vertebrate embryo, and nowhere is this is more evident than in the pharyngeal region. Each of the distinct segmented regions has a unique pattern of Hox expression, which conveys crucial positional information to the cells and tissues within it. In the context of pharyngeal organ development, molecular data suggest that HOXA3 is responsible for specifying organ identity within the third pharyngeal pouch, and in its absence, thymus and parathyroid organogenesis fails to proceed normally. Recent studies comprising a series of Hoxa3 mutations identified specific spatial and temporal roles for HOXA3 in pharyngeal organ development, including both cell-autonomous and non-autonomous functions, revealing a system that is more complex than originally thought. Here, we will review the current understanding of the role of Hox genes in the early embryonic development of the pharyngeal organs in the mouse, with a particular focus on the function of HOXA3 in thymus and parathyroid organogenesis.

Assessment and management of asthma and chronic obstructive pulmonary disease in Australian general practice.

BACKGROUND: Dispensing data suggest potential issues with the quality use of medicines for airways disease. OBJECTIVE: The objective of this article was to describe the management of asthma and chronic obstructive pulmonary disease (COPD) in general practice, and investigate the appropriateness of prescribing. METHODS: The method used for this study consisted of a national cross­sectional survey of 91 Australian general practitioners (GPs) participating in the Bettering the Evaluation and Care of Health (BEACH) program. RESULTS: Data were available for 2589 patients (288 asthma; 135 COPD). For the patients with asthma, GPs classified asthma as well controlled in 76.4%; 54.3% were prescribed inhaled corticosteroids (ICS), mostly (84.9%) as combination therapy, and mostly at moderate-high dose; only 26.3% had a written action plan. GPs classified COPD as mild for 42.9%. Most patients with COPD (60.9%) were prescribed combination ICS therapy and 36.7% were prescribed triple therapy. DISCUSSION: There were substantial differences between guideline-based and GP- recorded assessment and prescription for asthma and COPD. Further research is needed to improve care and optimise patient outcomes with scarce health resources.