A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-gamma) receptor signaling. Mal-dependent IFN-gamma receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-gamma signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-gamma-related diseases including autoimmunity and cancer

Physical functioning limitations and physical activity of people experiencing homelessness: A review

This review will comprehensively evaluate physical functioning and physical activity in people experiencing homelessnes

High-cost, high-need users of acute unscheduled HIV care: a cross-sectional study.

Background High-cost, high-need users are defined as patients who accumulate large numbers of emergency department visits and hospital admissions that might have been prevented by relatively inexpensive early interventions and primary care. This phenomenon has not been previously described in HIV-infected individuals. Methods We analyzed the health records of HIV-infected individuals using scheduled or unscheduled inpatient or outpatient health care in St James's Hospital, Dublin, Ireland, from October 2014 to October 2015. Results Twenty-two of 2063 HIV-infected individuals had a cumulative length of stay >30 days in the study period. These individuals accrued 99 emergency department attendances and 1581 inpatient bed days, with a direct cost to the hospital of >€1 million during the study period. Eighteen of 22 had potentially preventable requirements for unscheduled care. Two of 18 had a late diagnosis of HIV. Sixteen of 18 had not been successfully engaged in outpatient HIV care and presented with consequences of advanced HIV. Fourteen of 16 of those who were not successfully engaged in care had ≥1 barrier to care (addiction, psychiatric disease, and/or homelessness). Conclusions A small number of HIV-infected individuals account for a high volume of acute unscheduled care. Intensive engagement in outpatient care may prevent some of this usage and ensuing costs

Outcomes of the LEAP feasibility trial-A low-threshold, exercise programme with protein supplementation to target frailty and poor physical functioning in people experiencing homelessness and addiction issues.

BackgroundPeople experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how strategies to target physical functioning deficits and frailty work in practice in this group. The primary aim of this study was to explore the feasibility of an exercise intervention with protein supplementation to target physical functioning and frailty in people experiencing homelessness evaluated by recruitment and retention rates, adherence to the exercise sessions and protein supplement, adverse effects, programme feedback and characteristics of non-returners, sporadic and frequent attenders. The secondary aim was to evaluate changes in effectiveness outcomes of grip strength, muscle mass, lower extremity physical function, pain, frailty, and risk of malnutrition.MethodThis prospective single-arm study evaluated the feasibility of a 16-week rolling, low-threshold, 'drop-in' once weekly exercise programme with protein supplementation. The main recruitment site was a day-service centre for people who are homeless. Feasibility was assessed by the recruitment and retention rates, adherence to the exercise sessions and protein supplement as well as adverse effects, programme feedback and evaluation of characteristics of non-returners, sporadic (≤50% of available sessions) and frequent attenders (≥50% of available sessions). Effectiveness outcomes included pain (Visual Analogue Scale), physical functioning and performance (hand-grip dynamometry, limb circumference, the Short Physical Performance Battery), frailty (SHARE-FI and Clinical Frailty Scale) and nutritional status (Mini Nutritional Assessment).ResultsThirty-one participants were recruited mean (SD) age 45(16) years. There was a recruitment rate of a median (IQR) of 2(1-3) new participants per week. The retention rate was 45% (n = 14) to the main recruitment site. Adherence to the exercise sessions and nutritional intervention was 90% and 100% respectively. Three adverse events were recorded during 74 interventions over the 16-week programme. The acceptability of the programme was highlighted in participant feedback. Characteristics of frequent returners (≥50%) were older age, female, more stably housed and more stable in addiction. The programme did not induce any changes in effectiveness outcomes.ConclusionThe feasibility of this programme was demonstrated. Overall, the programme was well received with higher retention rates in older participants, females, those more stably housed and those stable in addiction. A higher powered, more intense programme is needed to demonstrate programme effectiveness

The unmet rehabilitation needs in an inclusion health integrated care programme for homeless adults in Dublin, Ireland.

BACKGROUND People who become homeless have higher morbidity and mortality, use a disproportionate amount of healthcare resources, and generate a large volume of potentially preventable healthcare and other costs compared to more privileged individuals. Although access to rehabilitation is a human right under article 26 of the United Nations Convention on the Rights of Persons with Disabilities, the rehabilitation needs of individuals with homelessness have not been explored, and this project's purpose was to establish a baseline of need for this cohort. METHODS A prospective audit of case discussions at an inclusion health service over a 2-month period in 2018. RESULTS Four multidisciplinary inclusion health clinics were observed with over 20 cases discussed in each and data were extracted using a bespoke audit data extraction tool. The inclusion health needs were diverse and complex with many unmet rehabilitation needs. Physical and cognitive rehabilitation needs were identified in over 50% of cases discussed. Musculoskeletal problems and acquired brain injuries were the most common cause of activity limitation. Most had concurrent medical conditions and addiction and/or mental health needs. None had access to rehabilitation services. CONCLUSION The results of this study show that the rehabilitative needs of this cohort are significant and are not being met through traditional models of care. We are currently exploring innovative ways to provide appropriate services to these individuals

Usage of unscheduled hospital care by homeless individuals in Dublin, Ireland: a cross-sectional study.

OBJECTIVES: Homeless people lack a secure, stable place to live and experience higher rates of serious illness than the housed population. Studies, mainly from the USA, have reported increased use of unscheduled healthcare by homeless individuals.We sought to compare the use of unscheduled emergency department (ED) and inpatient care between housed and homeless hospital patients in a high-income European setting in Dublin, Ireland. SETTING: A large university teaching hospital serving the south inner city in Dublin, Ireland. Patient data are collected on an electronic patient record within the hospital. PARTICIPANTS: We carried out an observational cross-sectional study using data on all ED visits (n=47 174) and all unscheduled admissions under the general medical take (n=7031) in 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The address field of the hospital's electronic patient record was used to identify patients living in emergency accommodation or rough sleeping (hereafter referred to as homeless). Data on demographic details, length of stay and diagnoses were extracted. RESULTS: In comparison with housed individuals in the hospital catchment area, homeless individuals had higher rates of ED attendance (0.16 attendances per person/annum vs 3.0 attendances per person/annum, respectively) and inpatient bed days (0.3 vs 4.4 bed days/person/annum). The rate of leaving ED before assessment was higher in homeless individuals (40% of ED attendances vs 15% of ED attendances in housed individuals). The mean age of homeless medical inpatients was 44.19 years (95% CI 42.98 to 45.40), whereas that of housed patients was 61.20 years (95% CI 60.72 to 61.68). Homeless patients were more likely to terminate an inpatient admission against medical advice (15% of admissions vs 2% of admissions in homeless individuals). CONCLUSION: Homeless patients represent a significant proportion of ED attendees and medical inpatients. In contrast to housed patients, the bulk of usage of unscheduled care by homeless people occurs in individuals aged 25-65 years

Data from: Usage of unscheduled hospital care by homeless individuals in Dublin, Ireland: a cross-sectional study

Objectives: Homeless people lack a secure, stable place to live, and experience higher rates of serious illness than the housed population. Studies, mainly from the US, have reported increased use of unscheduled health care by homeless individuals. We compared the use of unscheduled ED and inpatient care between housed and homeless hospital patients in a high-income European setting. Setting: A large university teaching hospital serving the south inner city in Dublin, Ireland. Patient data is collected on an electronic patient record within the hospital. Participants: We carried out an observational cross-sectional study using data on all ED visits (n=47,174) and all unscheduled admissions under the general medical take (n=7,031) in 2015. Primary and Secondary Outcome Measures: The address field of the hospital’s electronic patient record was used to identify patients living in emergency accommodation or rough sleeping (hereafter referred to as homeless). Data on demographic details, length of stay and diagnoses was extracted. Results: In comparison to housed individuals in the hospital catchment area, homeless individuals had higher rates of ED attendance (0.16 attendances per person/annum vs 3.0 attendances per person/annum respectively) and inpatient bed days (0.3 bed days per person/annum vs 4.4 bed days per person/annum. The rate of leaving ED before assessment was higher in homeless individuals (40% of ED attendances vs 15% of ED attendances in housed individuals). The mean age of homeless medical inpatients was 44.19 (95% CI 42.98-45.40), whereas that of housed patients was 61.20 (95% CI 60.72-61.68). Homeless patients were more likely to terminate an inpatient admission against medical advice (15% of admissions vs 2% of admissions in homeless individuals). Conclusion: Homeless patients represent a significant proportion of ED attendees and medical inpatients. In contrast to housed patients, the bulk of usage of unscheduled care by homeless people occurs in individuals younger than 65

Interferon Gamma Release Assays for the Diagnosis of Latent TB Infection in HIV-Infected Individuals in a Low TB Burden Country

<div><h3>Background</h3><p>Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting.</p> <h3>Methodology/Principal Findings</h3><p>T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar’s test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1–1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02).</p> <h3>Conclusions/Significance</h3><p>In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.</p> </div