Extended cost-effectiveness analysis of interventions to improve uptake of diabetes services in South Africa.

The rising prevalence of diabetes in South Africa (SA), coupled with significant levels of unmet need for diagnosis and treatment, results in high rates of diabetes-associated complications. Income status is a determinant of utilization of diagnosis and treatment services, with transport costs and loss of wages being key barriers to care. A conditional cash transfer (CCT) programme, targeted to compensate for such costs, may improve service utilization. We applied extended cost-effectiveness analysis (ECEA) methods and used a Markov model to compare the costs, health benefits and financial risk protection (FRP) attributes of a CCT programme. A population was simulated, drawing from SA-specific data, which transitioned yearly through various health states, based on specific probabilities obtained from local data, over a 45-year time horizon. Costs and disability-adjusted life years (DALYs) were applied to each health state. Three CCT programme strategies were simulated and compared to a 'no programme' scenario: (1) covering diagnosis services only; (2) covering treatment services only; (3) covering both diagnosis and treatment services. Cost-effectiveness was reported as incremental net monetary benefit (INMB) using a cost-effectiveness threshold of USD3015 per DALY for SA, while FRP outcomes were reported as catastrophic health expenditure (CHE) cases averted. Distributions of the outcomes were reported by income quintile and sex. Covering both diagnosis and treatment services for the bottom two quintiles resulted in the greatest INMB (USD22 per person) and the greatest CHE cases averted. There were greater FRP benefits for women compared to men. A CCT programme covering diabetes diagnosis and treatment services was found to be cost-effective, when provided to the poorest 40% of the SA population. ECEA provides a useful platform for including equity considerations to inform priority setting and implementation policies in SA.

Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

BACKGROUND AND OBJECTIVE: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. METHODS: Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. RESULTS: The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. CONCLUSIONS: Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

"There's Something to Remind You that Everything Is Okay": Australian Trans Young People and the Presence of Animals in Interactions With Healthcare Professionals.

While animals have long been a focus in therapeutic spaces for young people via approaches such as animal-assisted therapies, there is a sense in which such approaches overlook the broader contribution that animals play by being present in young people's lives. In this article, we explore how the presence of animals (both physical and psychological) in interactions with healthcare professionals may hold specific meaning for trans young people living in Australia. Participants were recruited through Parents of Gender Diverse Children. Interviews were conducted in November 2021 with 17 trans young people and one of each of their parents living in Australia. All interviews were audio recorded, transcribed, and analyzed using thematic analysis. Two main themes were developed: (1) how healthcare professionals respond to conversations about animals and (2) the beneficial role of the presence of animals. The article concludes by discussing the importance of thinking about the presence of animals beyond existing frameworks and recognizing the value placed on the presence of animals by trans young people.

Costs of seasonal influenza vaccination in South Africa.

BACKGROUND: Influenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010. METHODS: We adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country-specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key-informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs. RESULTS: Total financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively. CONCLUSION: We adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost-effectiveness analyses of seasonal influenza vaccination programmes.

The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals.

Objectves: The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity. Methods: Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m 2 (>25kg/m 2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses). Anticipated results: The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed. Trial registration: Current Controlled Trials ISRCTN12595520.

While most people infected with COVID-19 recover within a short amount of time, some people continue to have symptoms for 12 weeks or longer. This condition is known as Long COVID. Roughly two-thirds of people with Long COVID are overweight, a proportion similar to that found in the general population. Being overweight may worsen symptoms such as fatigue, breathlessness and pains. Weight management programmes in adults with overweight/obesity can reduce such symptoms, however we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported remotely, in people with Long COVID. The trial is conducted with 240 people with Long COVID, identified through their GP, patient groups, social media, or newspaper advertisements. A total of 120 individuals will receive the personalised, professionally supported weight management programme (treatment group), and 120 participants are allocated to usual care (control group). The one-year long weight management programme involves 12 weeks of total diet replacement (TDR) using soups and shakes, followed by food reintroduction and weight maintenance. Food based alternatives are available to those who are unable, or prefer not to, follow the TDR approach. The two groups will be compared for Long COVID symptoms, weight loss, quality of life and value for money after six months. After six months, the weight management programme will also be provided for the control group. Experiences while on the programme will be documented for 12 months for all participants. People with Long COVID have been involved extensively in developing this project. Their priorities are to reduce symptoms like fatigue, breathlessness and pain. They are keen to explore if effective weight management would help their symptoms and overall functioning, especially a programme that can be followed remotely from home. A group of patients and other stakeholders has been set up to provide advice throughout the project.

Inpatient Care Costs of COVID-19 in South Africa's Public Healthcare System.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a devastating impact globally, with severe health and economic consequences. To prepare health systems to deal with the pandemic, epidemiological and cost projection models are required to inform budgets and efficient allocation of resources. This study estimates daily inpatient care costs of COVID-19 in South Africa, an important input into cost projection and economic evaluation models. METHODS: We adopted a micro-costing approach, which involved the identification, measurement and valuation of resources used in the clinical management of COVID-19. We considered only direct medical costs for an episode of hospitalisation from the South African public health system perspective. Resource quantities and unit costs were obtained from various sources. Inpatient costs per patient day was estimated for consumables, capital equipment and human resources for three levels of inpatient care - general wards, high care wards and intensive care units (ICUs). RESULTS: Average daily costs per patient increased with the level of care. The highest average daily cost was estimated for ICU admissions - 271 USD to 306 USD (financial costs) and ~800 USD to 830 USD (economic costs, excluding facility fee) depending on the need for invasive vs. non-invasive ventilation (NIV). Conversely, the lowest cost was estimated for general ward-based care - 62 USD to 79 USD (financial costs) and 119 USD to 278 USD (economic costs, excluding facility fees) depending on the need for supplemental oxygen. In high care wards, total cost was estimated at 156 USD, financial costs and 277 USD, economic costs (excluding facility fees). Probabilistic sensitivity analyses suggest our costs estimates are robust to uncertainty in cost inputs. CONCLUSION: Our estimates of inpatient costs are useful for informing budgeting and planning processes and cost-effectiveness analysis in the South African context. However, these estimates can be adapted to inform policy decisions in other context.

Animals in Disaster Social Work: An Intersectional Green Perspective Inclusive of Species.

Disasters do not just affect humans. And humans do not only live with, care for or interact with other humans. In this conceptual article, we explain how animals are relevant to green and disaster social work. Power, oppression and politics are our themes. We start the discussion by defining disasters and providing examples of how three categories of animals are affected by disasters, including in the current COVID-19 pandemic. They are: companion animals (pets), farmed animals (livestock) and free-living animals (wildlife), all of whom we classify as oppressed populations. Intersectional feminist, de-colonising and green social work ideas are discussed in relation to disaster social work. We argue that social work needs to include nonhuman animals in its consideration of person-in-environment, and offer an expanded version of feminist intersectionality inclusive of species as a way forward.

The Link Between Domestic Violence and Abuse and Animal Cruelty in the Intimate Relationships of People of Diverse Genders and/or Sexualities: A Binational Study.

Over the past three decades, a growing body of research has focused on experiences of domestic violence and abuse (DVA) among people of diverse genders and/or sexualities. Missing, however, has been a focus on what is known as "the link" between DVA and animal cruelty with regard to people of diverse genders and/or sexualities. The present article reports on a study of 503 people living in either Australia or the United Kingdom, who reported on both their intimate human relationships and their relationships with animals, including relationships that were abusive. In terms of "the link," a fifth of respondents who had experienced violence or abuse also reported that animal cruelty had been perpetuated by the violent or abusive partner. Statistical interactions were found between having witnessed animal cruelty perpetrated by a partner, gender and sexuality, and both psychological distress and social connectedness. Female participants who had witnessed animal cruelty reported greater psychological distress and lower levels of social support, and both lesbian and bisexual participants who had witnessed animal cruelty reported lower levels of social support. The article concludes by considering the implications of these findings for future research and service provision.

A cost-effectiveness analysis of South Africa's seasonal influenza vaccination programme.

BACKGROUND: Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months. METHOD: We employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination. RESULTS: The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden. CONCLUSION: South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.

Influenza economic burden among potential target risk groups for immunization in South Africa, 2013-2015.

BACKGROUND: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries. METHODS: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index. RESULTS: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death. CONCLUSION: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.

Influenza disease burden among potential target risk groups for immunization in South Africa, 2013-2015.

BACKGROUND: Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013-2015. METHODS: We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013-2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6-59 months; (ii) individuals aged 5-64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population. RESULTS: During 2013-2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6-59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness. CONCLUSION: Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization.

Service provider recognition of the significance of animal companionship among trans and cisgender women of diverse sexualities.

Extensive literature reveals the many health benefits animal companions can bring to the humans who live with them. However, much of this work has taken place with heterosexual and cisgender populations. To address this gap, we conducted qualitative interviews with 19 trans and cisgender women of diverse sexualities in Australia who reported having significant relationships with animal companions. In this article, we explore the benefits of healthcare providers (e.g. doctors, counsellors) recognising the potential significance of interspecies companionship for the health of trans and cisgender women of diverse sexualities. Findings relating to interactions with animal service providers are used to further illustrate themes of recognition and non-recognition as they relate to the women's genders, sexualities, and relationships with animal companions. In the discussion we consider some of the contextual challenges for such recognition to occur in service provision. Suggestions are then offered in relation to how providers might think about service provision which is both inclusive of all women and takes into account close connections with animal companions.

A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder.

Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice.

Type 1 diabetes (T1D) is a chronic multi-factorial disorder characterized by the immune-mediated destruction of insulin-producing pancreatic beta cells. Variations at a large number of genes influence susceptibility to spontaneous autoimmune T1D in non-obese diabetic (NOD) mice, one of the most frequently studied animal models for human disease. The genetic analysis of these mice allowed the identification of many insulin-dependent diabetes (Idd) loci and candidate genes, one of them being Cd101. CD101 is a heavily glycosylated transmembrane molecule which exhibits negative-costimulatory functions and promotes regulatory T (Treg) function. It is abundantly expressed on subsets of lymphoid and myeloid cells, particularly within the gastrointestinal tract. We have recently reported that the genotype-dependent expression of CD101 correlates with a decreased susceptibility to T1D in NOD.B6 Idd10 congenic mice compared to parental NOD controls. Here we show that the knockout of CD101 within the introgressed B6-derived Idd10 region increased T1D frequency to that of the NOD strain. This loss of protection from T1D was paralleled by decreased Gr1-expressing myeloid cells and FoxP3+ Tregs and an enhanced accumulation of CD4-positive over CD8-positive T lymphocytes in pancreatic tissues. As compared to CD101+/+ NOD.B6 Idd10 donors, adoptive T cell transfers from CD101-/- NOD.B6 Idd10 mice increased T1D frequency in lymphopenic NOD scid and NOD.B6 Idd10 scid recipients. Increased T1D frequency correlated with a more rapid expansion of the transferred CD101-/- T cells and a lower proportion of recipient Gr1-expressing myeloid cells in the pancreatic lymph nodes. Fewer of the Gr1+ cells in the recipients receiving CD101-/- T cells expressed CD101 and the cells had lower levels of IL-10 and TGF-ß mRNA. Thus, our results connect the Cd101 haplotype-dependent protection from T1D to an anti-diabetogenic function of CD101-expressing Tregs and Gr1-positive myeloid cells and confirm the identity of Cd101 as Idd10.

Promoting gender responsive support for women inmates: a case study from inside a prison.

PURPOSE: Most women who serve time in prison will eventually be released and expected to reintegrate back into society. To maximize the chances of success, careful support is usually required. An example of this support work was the Healthy Relationships Program (HRP, 2016) offered to women inmates of the Adelaide Women's Prison (South Australia) pre-release. The content of the HRP was influenced by a gender-responsive framework and constructed as a social work program. The purpose of this paper is to report on a small qualitative study that used semi-structured interviews pre- and post-program to explore women participants' expectations, perceptions and experiences of the program. In this paper, the focus is on the women inmates' interview transcripts where a thematic analysis was conducted. Two main research questions drove this analysis. First: How did the women experience the HRP? Second: What does their reported experience reveal about the ongoing need for gender-responsive support? The key findings are that domestic violence and relationships with children are strong motivators for participation in programs; therefore, gender-responsive support is still required in prison programs. However, the paper also advocates that future iterations of gender-responsive support and social work interventions become more consciously intersectional feminist in orientation. DESIGN/METHODOLOGY/APPROACH: A qualitative design was used to explore what women thought the HRP taught them. Individual face-to-face interviews were used to explore women's perceptions, ideas and experiences of healthy relationships. Thematic analysis was used to draw out the themes across interviews. FINDINGS: The key arguments made are that gender-responsive support is still required but that future iterations of gender-responsive support become more consciously intersectional feminist in orientation. RESEARCH LIMITATIONS/IMPLICATIONS: The researchers experienced strict time restrictions to conduct interviews and therefore depth was somewhat compromised. To try and compensate for this restriction, the researchers visited potential participants as part of program recruitment and information sharing to help enable and build general rapport before the interviews. Time restrictions and prison security protocols did not allow for researchers to check transcripts with the women. PRACTICAL IMPLICATIONS: Reporting on this case study also showed that social work practice can influence relationships with institutions, such as prisons, that perpetrate marginalization and therefore enable a setting that facilitates safe participation in programs. SOCIAL IMPLICATIONS: Gender-responsive frameworks provide the much needed validation of gender differences, but also require a feminist intersectional lens to more consciously aid in the conceptualization and evaluation of future programs for women in prison. It is this intersectional lens that is more likely to bring multiple experiences of oppression into focus so that personal issues and problems can be analyzed in a richer wider social context, particularly intersections between gender, class and/ethnicity race. ORIGINALITY/VALUE: This paper has reported on women's expectations and experiences of a health relationships program and provides insight and learnings for future practitioners intending to run similar programs. Overall, the women participants were able to articulate their own personal learnings about interpersonal relationships and were able to acknowledge the impacts of abuse and violence in their lives in the program.

People of Diverse Genders and/or Sexualities Caring For and Protecting Animal Companions in the Context of Domestic Violence.

This article reports on a thematic analysis of open-ended questions about how humans respond to violence directed toward animals in the context of violent human relationships, derived from an Australian-U.K. survey of people of diverse genders and/or sexualities. From the 137 responses, three major themes were identified: (a) animals are an important source of support, (b) humans actively protect animal companions, and (c) witnessing animal abuse can trigger leaving violent relationships. The findings offer unique insights for practitioners into the help-seeking needs of people of diverse genders and/or sexualities who live with animal companions in the context of domestic violence.

Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice.

By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we demonstrated previously that the type 1 diabetes (T1D) protection associated with the insulin-dependent diabetes (Idd)10 locus on chromosome 3, originally identified by linkage analysis, was in fact due to three closely linked Idd loci: Idd10, Idd18.1, and Idd18.3. In this study, we define two additional Idd loci--Idd18.2 and Idd18.4--within the boundaries of this cluster of disease-associated genes. Idd18.2 is 1.31 Mb and contains 18 genes, including Ptpn22, which encodes a phosphatase that negatively regulates T and B cell signaling. The human ortholog of Ptpn22, PTPN22, is associated with numerous autoimmune diseases, including T1D. We, therefore, assessed Ptpn22 as a candidate for Idd18.2; resequencing of the NOD Ptpn22 allele revealed 183 single nucleotide polymorphisms with the C57BL/6J (B6) allele--6 exonic and 177 intronic. Functional studies showed higher expression of full-length Ptpn22 RNA and protein, and decreased TCR signaling in congenic strains with B6-derived Idd18.2 susceptibility alleles. The 953-kb Idd18.4 locus contains eight genes, including the candidate Cd2. The CD2 pathway is associated with the human autoimmune disease, multiple sclerosis, and mice with NOD-derived susceptibility alleles at Idd18.4 have lower CD2 expression on B cells. Furthermore, we observed that susceptibility alleles at Idd18.2 can mask the protection provided by Idd10/Cd101 or Idd18.1/Vav3 and Idd18.3. In summary, we describe two new T1D loci, Idd18.2 and Idd18.4, candidate genes within each region, and demonstrate the complex nature of genetic interactions underlying the development of T1D in the NOD mouse model.

Surfactant and varespladib co-administration in stimulated rat alveolar macrophages culture.

Acute lung injury is a life-threatening condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing. sPLA2 activity, free fatty acids, tumour necrosis factor-α (TNF-α) and protein concentrations were measured in culture supernatants. Treatment with varespladib (p=0.019) and varespladib + surfactant (p=0.013), reduced the enzyme activity by approximately 15% from the basal level measured in the untreated cultures. Surfactant, varespladib and varespladib + surfactant, respectively decreased free fatty acids by -45% (p=0.045), - 62% (p=0.009) and -48% (p=0.015), from the baseline concentration of the untreated cultures. Varespladib and poractant- α co-administration reduces sPLA2 activity and free fatty acids release in cultured rat alveolar macrophages, although a clear drug synergy was not evident. Since co-administration may be useful to reduce inflammation and surfactant inactivation in acute lung injury, further in vivo studies are warranted to verify its clinical usefulness.

Anti-inflammatory effects of varespladib methyl in diabetic patients with acute coronary syndrome.

PURPOSE: Secretory phospholipase A(2) group IIA (sPLA(2-)IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA(2)-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA(2) inhibition. METHODS: The effects of the sPLA(2) inhibitor varespladib methyl 500 mg daily and placebo on serial changes in inflammatory and lipid biomarkers were examined in 624 ACS patients who were treated with standard of care including atorvastatin 80 mg daily. RESULTS: Compared with non-diabetic patients, diabetic patients had higher baseline concentrations of sPLA(2)-IIA (p = 0.0066), hs-CRP (p = 0.0155), and IL-6 (p = 0.009). At 8 weeks of treatment (primary endpoint), varespladib methyl reduced median sPLA(2)-IIA levels by -83.6% in diabetic patients and by -82.4% in non-diabetic patients (p = 0.33). Median hs-CRP and IL-6 levels were reduced in both varespladib methyl-treated diabetic and non-diabetic patients, but these differences were not statistically significantly different at 8 weeks (p = 0.57 and p = 0.97 respectively). CONCLUSIONS: Varespladib significantly reduces the post-ACS inflammatory response in those with and without diabetes. These responses were greater in diabetic subjects compared to non-diabetic subjects.