Disease Focused Integrated Care - a New Model of Healthcare Delivery for the Treatment of Skin Cancer.

Introduction: As the most common cancer in Australia, skin cancer generates a considerable health burden. This study outlines the establishment of a new model of integrated care for the diagnosis and management of skin cancer. Methods: A new model of integrated care was established to provide access to all aspects of skin cancer management. General practitioners (GPs) were upskilled through hands-on training and a 6-month skin cancer education program and partnered with specialist Dermatologists and Plastic Surgeons co-located in the same clinic. Data including median wait times between the initial consultation and treatment were prospectively collected and compared patients seen through the integrated pathway to patients referred from their primary GP to specialist Dermatologists and Plastic Surgeons directly (non-integrated pathway). The percentage of patients needing co-consultation with a specialist in the integrated pathway was also measured over time. Results: A total of 25341 patients were seen from the commencement of the clinic in August 2015 to June 2021. In 2017 and 2018 the median wait time to be treated was 7 days for the integrated model compared to 54 days (2017) and 46 days (2018) for non-integrated care (p < 0.0001). The percentage of GPs requesting specialist co-consultations for assessment of skin cancer fell from 98% in 2015, to 5.6% in 2021. Histopathology shows that 66% of lesions excised by GPs in this model were malignant or pre-malignant. Conclusions: This study firstly shows a significant reduction in time to treatment in an integrated skin cancer model over traditional models of health. Secondly it demonstrates GP upskilling over time in the integrated program. Integrating GP and specialist medical practitioners in the treatment of skin cancer offers potential for more efficient, accessible, and affordable care. This cooperative, co-located model may provide a template for the integrating the management of other conditions.

Translating Health Coaching Training into Clinical Practice.

Health coaching can benefit people with managing chronic conditions. It considers people's motivations, is person-centred and has the capacity to promote healthy lifestyles and address chronic disease risk factors. However, how health coaching training is translated into routine clinical practice at unit and service levels has been under explored. A metropolitan local health district in Sydney, Australia provided coaching training to health professionals, but the extent to which coaching skills were translated into clinical practice was unknown. A redesign methodology was used to identify barriers and facilitators for training-to-practice translation. Survey and workshop findings indicated that participants were satisfied with the coaching training but found it challenging to apply in clinical practice. Identified opportunities to support the application of health coaching were tailored practical training, post training support, and consensus on the definition of health coaching. Solutions were to develop an internal practical training program, use consistent terminology, and embed organisational support. Adoption of health coaching needs to occur on three levels; individual, workplace and organisation to ensure effective health care delivery. This case study demonstrates the importance of evaluation and diagnostics of contextual barriers and enablers to inform translation into practice.

Biomimetic recyclable microgels for on-demand generation of hydrogen peroxide and antipathogenic application.

Microgels that can generate antipathogenic levels of hydrogen peroxide (H2O2) through simple rehydration in solutions with physiological pH are described herein. H2O2 is a widely used disinfectant but the oxidant is hazardous to store and transport. Catechol, an adhesive moiety found in mussel adhesive proteins, was incorporated into microgels, which generated 1-5 mM of H2O2 for up to four days as catechol autoxidized. The sustained release of low concentrations of H2O2 was antimicrobial against both gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria and antiviral against both non-enveloped porcine parvovirus (PPV) and enveloped bovine viral diarrhea virus (BVDV). The amount of released H2O2 is several orders of magnitude lower than H2O2 concentration previously reported for antipathogenic activity. Most notably, these microgels reduced the infectivity of the more biocide resistant non-envelope virus by 3 log reduction value (99.9% reduction in infectivity). By controlling the oxidation state of catechol, microgels can be repeatedly activated and deactivated for H2O2 generation. These microgels do not contain a reservoir for storing the reactive H2O2 and can potentially function as a lightweight and portable dried powder source for the disinfectant for a wide range of applications. STATEMENT OF SIGNIFICANCE: Researchers have designed bioadhesives and coatings using the adhesive moiety catechol to mimic the strong adhesion capability of mussel adhesive proteins. During catechol autoxidation, hydrogen peroxide (H2O2) is generated as a byproduct. Here, catechol was incorporated into microgels, which can generate millimolar levels of H2O2 by simply hydrating the microgels in a solution with physiological pH. The sustained release of H2O2 was both antimicrobial and antiviral, inactivating even the more biocide resistant non-enveloped virus. These microgels can be repeatedly activated and deactivated for H2O2 generation by incubating them in solutions with different pH. This simplicity and recyclability will enable this biomaterial to function as a lightweight and portable source for the disinfectant for a wide range of applications.

Improving health literacy through adult basic education in Australia.

Adults with low literacy are less empowered to take care of their health, have poorer health outcomes and higher healthcare costs. We facilitated partnerships between adult literacy teachers and community health providers to deliver a health literacy training program in adult basic education classrooms. Following course completion we interviewed 19 adult education teachers (15 delivering the health literacy program; 4 delivering standard literacy classes) and four community health providers (CHPs) about their experiences, and analysed transcripts using Framework analysis. Written feedback from eight teachers on specific course content was added to the Framework. Health literacy teachers reported a noticeable improvement in their student's health behaviours, confidence, vocabulary to communicate about health, understanding of the health system and language, literacy and numeracy skills. CHP participation was perceived by teachers and CHPs as very successful, with teachers and CHPs reporting they complemented each other's skills. The logistics of coordinating CHPs within the constraints of the adult education setting was a significant obstacle to CHP participation. This study adds to existing evidence that health is an engaging topic for adult learners, and health literacy can be successfully implemented in an adult basic learning curriculum to empower learners to better manage their health. Health workers can deliver targeted health messages in this environment, and introduce local health services. Investment in adult literacy programs teaching health content has potential both to meet the goals of adult language and literacy programs and deliver health benefit in vulnerable populations.

The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

Dans cette étude pilote, 10 chiens avec un ostéosarcome (OSA) ont été traités par amputation et chimiothérapie subséquente avec du carboplatin (300 mg/m2 IV q3sem × 4 doses) suivi de phosphate de toceranib (2,75 mg/kg PO q48h débutant au jour 14 suivant le carboplatin). Un suivi clinique mensuel et une mesure des taux sériques du facteur de croissance de l'endothélium vasculaire (FCEV) et de la matrice de la métalloprotéinase-9 (MMP-9) ont été obtenus. Aucun chien ne fut retiré de l'étude pour cause de toxicité. Les niveaux de FCEV et MMP-9 n'ont pas changé dans le temps. Sept chiens sont décédés dues à une rechute locale et/ou des métastases osseuses et les autres sont morts d'autres causes. La durée médiane de survie libre d'OSA était de 238 j avec 34 % de survie sans progression de la condition après 1 an. La durée de survie médiane était de 253 j avec 30 % en vie après 1,5 an et 10 % en vie après 2 ans. Bien que ce traitement ait été bien toléré, les temps de survie n'ont pas excédé les résultats publiés antérieurement pour des chiens traités par amputation et chimiothérapie uniquement.(Traduit par Docteur Serge Messier).

Assessment of the prevalence and clinical features of cryptogenic epilepsy in dogs: 45 cases (2003-2011).

OBJECTIVE: To determine the prevalence and clinical features of cryptogenic epilepsy among dogs. DESIGN: Retrospective case series. ANIMALS: 214 client-owned dogs with onset of epileptic seizures at ≥ 7 years of age. PROCEDURES: A diagnostic imaging database was searched for dogs with symptomatic or cryptogenic epilepsy. Signalment, seizure history, and diagnostic information were recorded. Information regarding seizure frequency, administration of antiepileptic drugs (AEDs), owners' perceptions regarding quality of life, survival times, and causes of death for dogs with cryptogenic epilepsy was obtained via questionnaire. Variables were compared among dogs grouped according to diagnosis and age. RESULTS: 45 (21%) dogs had a diagnosis of cryptogenic epilepsy, and 169 (79%) had symptomatic epilepsy. In dogs 7 to 9 years and ≥ 10 years of age at the time of seizure onset, 31 of 106 (29%) and 14 of 108 (13%), respectively, had a diagnosis of cryptogenic epilepsy. At last follow-up, most (40 [89%]) dogs with cryptogenic epilepsy were receiving ≥ 1 AED. Thirty-one of 37 (84%) dogs typically had ≤ 1 seizure/mo following hospital discharge. Death was confirmed in 20 (44%) dogs with cryptogenic epilepsy and was related to seizures or AEDs in 7 Median survival time from onset of seizures was 52 months for all dogs with cryptogenic epilepsy. Median quality-of-life score (scale, 1 [poor] to 10 [excellent]) indicated by 34 owners of dogs with cryptogenic epilepsy was 10 before diagnosis and initiation of AED treatment and 8 afterward. CONCLUSIONS AND CLINICAL RELEVANCE: Cryptogenic epilepsy was diagnosed in a substantial proportion of dogs with an onset of epileptic seizures at ≥ 7 years of age. Seizure control was considered acceptable in most dogs.

Levetiracetam pharmacokinetics in healthy dogs following oral administration of single and multiple doses.

OBJECTIVE: To measure pharmacokinetics of levetiracetam (LEV) after single-dose oral administration in healthy dogs and determine whether pharmacokinetics changed after repeated oral dosing. ANIMALS: 6 healthy adult dogs. PROCEDURES: Pharmacokinetics were calculated following administration of a single dose (mean, 21.7 mg/kg, PO; day 1) and after administration of the last dose following administration for 6 days (20.8 to 22.7 mg/kg, PO, q 8 h; days 2 to 7). Plasma LEV concentrations were determined by use of high-pressure liquid chromatography. Pharmacokinetic data were analyzed by use of a 1-compartment model with first-order absorption. RESULTS: Peak concentration occurred 0.6 hours after administration of the first dose, with an absorption half-life of 0.06 hours. Minimal accumulation occurred over the 7 days, with only a slight increase in total area under the concentration-versus-time curve from 268.52 +/- 56.33 h x microg/mL (mean +/- SD) to 289.31 +/- 51.68 h x microg/mL after 7 days. Terminal half-life was 2.87 +/- 0.21 hours after the first dose and 3.59 +/- 0.82 hours after the last dose on day 7. Trough plasma concentrations were variable, depending on the time of day they were measured (morning trough concentration, 18.42 +/- 5.16 microg/mL; midday trough concentration, 12.57 +/- 4.34 microg/mL), suggesting a diurnal variation in drug excretion. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the pharmacokinetics of LEV did not change appreciably after administration of multiple doses over 7 days. Administration of LEV at a dosage of 20 mg/kg, PO, every 8 hours to healthy dogs yielded plasma drug concentrations consistently within the therapeutic range established for LEV in humans.

Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases.

A consistent feature of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF-kappaB transcription factors. In Epstein-Barr virus (EBV)-associated cases of cHL, expression of viral antigens most probably leads to NF-kappaB activation but for non-EBV-associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding IkappaB alpha, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non-EBV-associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non-EBV-associated cases but the majority of these cases had wild-type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series.

Assessment of the microbial quality of water offered to captive psittacine birds.

To investigate potential water-source microbes, 44 samples of water offered to individually caged psittacine birds were aseptically collected from 14 bird-owning households and evaluated for the presence of coliforms, Escherichia coli, heterotrophic bacteria, and Pseudomonas aeruginosa. No samples were positive for E. coli; however, 21 of 25 water samples (84%) from open containers and 7 of 19 samples (37%) from bottles exceeded US Environmental Protection Agency standards for coliforms. Fourteen of 24 open containers (58%) and 7 of 19 bottles (37%) grew heterotrophic bacteria that exceeded 500 colonies/ml. Pseudomonas aeruginosa was isolated from water samples from 1 open container and 1 bottle. These results suggest that potentially pathogenic bacteria can be found in water offered to companion psittacine birds. Additional studies are needed to assess whether these bacteria are clinically important causes of disease and to develop husbandry methods that will reduce contamination.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

OBJECTIVE: To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. ANIMALS: 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). PROCEDURES: In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). RESULTS: Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole < or = 0.4 microg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

A model for teaching raptor medicine in the veterinary curriculum.

Injured or sick wild avian species, especially raptors (birds of prey, including hawks, owls, falcons, and eagles), can present different challenges to veterinary students and veterinarians who are trained in companion avian medicine (e.g., parrot medicine). Proper capture and restraint, feeding, housing, and certain diagnostic and treatment techniques involving raptors require different skills, knowledge, and resources than working with parrots. We developed an innovative raptor medicine program that enables students to acquire proficiency in safe capture, restraint, and examination techniques and in common diagnostic and treatment procedures. A self-assessment survey was developed to determine students' confidence and proficiency in 10 procedures taught in the lab. Groups were compared by class status (Year 1 vs. Year 2 and 3) and level of prior raptor experience (non-experienced or experienced). In surveys conducted before and after teaching two sets of raptor training labs, students rated themselves significantly more proficient in all 10 diagnostic and treatment procedures after completing the two raptor laboratories. The greatest improvements were observed in technical skill procedures such as fluid administration, intramuscular injections, cloacal swabs, venipuncture, and bandaging. Our approach to incorporating elective wildlife learning experiences into the veterinary curriculum may be replicable in other veterinary schools, with or without a wildlife rehabilitation program.

A model for improving student confidence and experience in diagnostic sample collection and interpretation.

Confidence and proficiency in diagnosing and treating a variety of diseases is of obvious importance to veterinary students. Traditional teaching methods relying on live-animal laboratories or teaching-hospital cases may not provide the breadth and depth of experience necessary to promote optimal development of confidence and skills. These settings also raise concerns about expense, about animal welfare when animals are used in teaching laboratories, and about the stress and potential risks associated with client-owned pets in the teaching hospital. A one-week course implemented in our veterinary curriculum provides the opportunity for students to develop self-assurance and experience in sample collection and interpretation skills in a realistic, clinical-model setting. This course provides students with significantly improved levels of confidence when performing procedures and interpreting results from a variety of procedures and helps prepare them to become clinicians entering the practice of veterinary medicine.

Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma.

Somatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). Impairment of IkappaBalpha function results in deregulated NF-kappaB activity, a characteristic of HRS cells. The molecular basis for familial HL, which accounts for approximately 4% of all HL cases, is unclear. To date, familial HL cases have not been evaluated for germline NFKBIA mutations. We screened the entire NFKBIA gene in 8 individuals with familial HL but found no mutations in the coding region or promoter sequences. We identified the first germline NFKBIA missense mutation in a patient with presumed sporadic HL. The frequency of 4 polymorphisms within the NFKBIA gene and promoter region was investigated in a series of HL and control samples; no significant differences emerged but a novel polymorphism was identified in the promoter region. Overall, our results suggest that germline mutations of NFKBIA are not a significant cause of familial aggregation of HL but may contribute to inherited susceptibility to HL.

Viral IL-6-induced cell proliferation and immune evasion of interferon activity.

Lymphoma cells infected with Kaposi's sarcoma-associated herpesvirus are autocrine dependent on virus-derived interleukin-6 (IL-6), but not on cellular IL-6. During viral infection, host cells induce the antiviral factor interferon (IFN) to up-regulate p21, initiate cell cycle arrest, and inhibit virus replication. Viral IL-6, however, blocks IFN signaling. A viral transcriptional program exists in which only the viral IL-6 gene is directly activated by IFN-alpha, allowing the virus to modify its cellular environment by sensing and responding to levels of intracellular IFN signaling. The human cytokine cannot mimic this effect because IFN-alpha down-regulates the IL-6 receptor, gp80. Viral IL-6 bypasses the gp80 regulatory checkpoint by binding directly to the gp130 transducer molecule, resulting in tumor cell autocrine dependence on the viral cytokine for proliferation and survival.

Infection with Brugia microfilariae induces apoptosis of CD4(+) T lymphocytes: a mechanism of immune unresponsiveness in filariasis.

In humans infected with lymphatic filariasis, microfilaraemia [the presence of microfilariae (Mf) in the blood] is generally associated with both poor antigen (Ag)-specific proliferative responses and with protection from severe disease. Clonal deletion has been suggested as one possible mechanism by which parasite-reactive lymphocytes, that may be capable of mediating resistance and/or immunopathology, are silenced in asymptomatic carriers. In this study we demonstrate that splenic lymphocytes from mice infected with microfilariae of Brugia pahangi display an Ag-specific proliferative defect. However, these cells were not completely unresponsive since they produced high levels of Ag-specific IFN-gamma. Using TdT-mediated dUTP-biotin nick end labeling for flow cytometry, CD4(+) lymphocytes from Mf-infected mice cultured with Ag showed high levels of apoptosis when compared to those from L3-infected mice which proliferated well in response to Ag. Treatment of Ag-stimulated cultures with aminoguanidine (AMG), an inhibitor of inducible nitric oxide synthase, rescued the CD4(+) T cells from apoptosis and reversed the proliferative defect. Furthermore, carboxyfluorescein diacetate succinimidyl ester labeling allowed the visualization of dividing CD4(+) T cells in cultures from Mf-infected animals only in the presence of AMG. We hypothesize that CD4(+) T cells indirectly trigger their own apoptosis by secreting significant quantities of IFN-gamma resulting in the induction of high levels of nitric oxide, and the subsequent elimination of effector T cells. Our findings are the first direct evidence that infection with Brugia Mf can selectively induce lymphocyte apoptosis, a phenomenon that could contribute to the proliferative defect and parasite persistence associated with the microfilaraemic state in the infected human.