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BACKGROUND: The HeLP-GP trial aimed to increase the capacity of practice nurses to deliver weight management to overweight and obese patients through an intervention comprising a health check, a lifestyle app and/or telephone coaching. This paper describes implementation through the lens of organisational readiness with emphasis on the role of the practice nurse. METHODS: Routinely collected mixed method research data including practice surveys, field notes, and diaries and process data were mapped against the domains: motivation to implement, general capacity and intervention-specific capacity. RESULTS: Organisational readiness varied considerably, particularly the domain of intervention-specific capacity. Practice nurse turnover negatively impacted the implementation, affecting half of the practices. We observed a general lack of practice-based support for intervention delivery, and varying levels of interest, skill and confidence in delivering the intervention. Nurses struggled to complete the research and intervention tasks in a timely way. Conducting risk assessments and referring to coaching were generally not problematic; however, we noted lower confidence levels with the lifestyle app and instructing patients to use it. CONCLUSIONS: We found a lack of general 'readiness' inherent in the nursing role, particularly related to their capacity to complete intervention tasks and practice-level support to implement the intervention. For nurses in general practice to fulfil their potential in supporting patients to reduce risk and adopt healthier life choices, our study indicates that more could be done to improve their workforce positioning and remuneration, which may, in turn, improve continuity of care, retention and individual motivation.
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BACKGROUND: Nepal's low fertility rate and increasing life expectancy have resulted in a burgeoning older population. For millennia, filial piety shaped family cohesion and helped Nepali older adults achieve positive outcomes, but recently, it has been eroding. Furthermore, there are not enough institutional support options or alternatives to family-based care to deal with the biosocial needs of older adults. This study explored the association between family support and self-rated health among Nepali older adults. METHODS: A community-based cross-sectional survey in eastern Nepal's two districts, Sunsari and Morang, interviewed 847 older adults (≥ 60 years). The final analytical sample was 844. Participants were asked whether they received assistance with various aspects of daily life and activities of daily living from their families. Multivariable logistic regression examined the association between family support and self-rated health. RESULTS: Participants who received support with various aspects of daily life had 43% higher odds of good health, but after adjusting for control variables, the result only approached statistical significance (p = 0.087). Those who received family assistance with activities of daily living had nearly four times higher odds (OR: 3.93; 95% CI: 2.58 - 5.98) of reporting good health than participants who lacked this support. CONCLUSIONS: Given the important role of family support in Nepali older adults' health, government programs and policies should create a conducive environment to foster family-based care until more comprehensive policies for older adults' care can be put into effect. The results of this study can also help shape the global aging environment by highlighting the need for family support in older care, particularly in low-income nations with declining traditional care systems and weak social security policies.
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Actividades Cotidianas , Apoyo Familiar , Humanos , Anciano , Estudios Transversales , Nepal/epidemiología , EnvejecimientoRESUMEN
PURPOSE: To compare the effects of macular intraretinal hemorrhage (IRH) and macular hole (MH) on best-corrected visual acuity (BCVA) after displacement of submacular hemorrhage (SMH) due to retinal arterial macroaneurysm (RAM) rupture. METHODS: This multicenter retrospective study included 48 eyes with SMH due to RAM rupture. Cases underwent vitrectomy to displace SMH and were followed up for 6 months. We classified cases according to the presence of IRH and MH and compared the postoperative BCVA among the groups. RESULTS: We classified the eyes into IRH(+)MH(+) group (10 eyes), IRH(+)MH(-) group (23 eyes), and IRH(-)MH(-) group (15 eyes). The postoperative BCVA was significantly worse in the IRH(+)MH(+) and IRH(+)MH(-) groups than in the IRH(-)MH(-) group (0.91 ± 0.41 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/163, 0.87 ± 0.45, 20/148, and 0.18 ± 0.21, 20/30, respectively; P < 0.001). The postoperative central retinal thickness was significantly lower in the IRH(+) group (IRH(+)MH(+) and IRH(+)MH(-) groups combined) than in the IRH(-) group (IRH(-)MH(-) group) (121.4 ± 70.1 µ m and 174.3 ± 32.9 µ m, respectively, P = 0.008). The postoperative external limiting membrane and ellipsoid zone continuities were significantly discontinuous in the IRH(+) group ( P < 0.001, P = 0.001, respectively). The multiple linear regression analysis showed that both IRH(+)MH(+) and IRH(+)MH(-) were associated with the postoperative BCVA (regression coefficient, 0.799 and 0.711, respectively; P < 0.001 for both). CONCLUSION: Both IRH and MH were poor prognostic indicators in cases with SMH due to RAM rupture.
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Macroaneurisma Arterial de Retina , Perforaciones de la Retina , Humanos , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/etiología , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Macroaneurisma Arterial de Retina/complicaciones , Macroaneurisma Arterial de Retina/diagnóstico , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiología , Hemorragia Retiniana/cirugía , Pronóstico , Vitrectomía , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND: Australia has one of the highest rates of overweight and obesity in the developed world, and this increasing prevalence and associated chronic disease morbidity reinforces the importance of understanding the attitudes, views, and experiences of patients and health providers towards weight management interventions and programs. The purpose of this study was to investigate patients, family practitioners and family practice nurses' perceptions and views regarding the receipt or delivery of weight management within the context of the HeLP-GP intervention. METHODS: A nested qualitative study design including semi-structured interviews with family practitioners (n = 8), family practice nurses (n = 4), and patients (n = 25) attending family practices in New South Wales (n = 2) and South Australia (n = 2). The patient interviews sought specific feedback about each aspect of the intervention and the provider interviews sought to elicit their understanding and opinions of the strategies underpinning the intervention as well as general perceptions about providing weight management to their patients. Interviews were recorded and transcribed verbatim, and coding and management conducted using NVivo 12 Pro. We analysed the interview data using thematic analysis. RESULTS: Our study identified three key themes: long-term trusting and supportive relationships (being 'in it for the long haul'); initiating conversations and understanding motivations; and ensuring access to multi-modal weight management options that acknowledge differing levels of health literacy. The three themes infer that weight management in family practice with patients who are overweight or obese is challenged by the complexity of the task and the perceived motivation of patients. It needs to be facilitated by positive open communication and programs tailored to patient needs, preferences, and health literacy to be successful. CONCLUSIONS: Providing positive weight management in family practice requires ongoing commitment and an open and trusting therapeutic relationship between providers and patients. Behaviour change can be achieved through timely and considered interactions that target individual preferences, are tailored to health literacy, and are consistent and positive in their messaging. Ongoing support of family practices is required through funding and policy changes and additional avenues for referral and adjunctive interventions are required to provide comprehensive weight management within this setting.
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Medicina Familiar y Comunitaria , Medicina General , Humanos , Sobrepeso/prevención & control , Obesidad/epidemiología , Obesidad/prevención & control , Proyectos de InvestigaciónRESUMEN
Experimental autoimmune uveoretinitis (EAU) is an animal model of non-infectious uveitis and is developed by immunization with retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2) is responsible for regulating antioxidant and inflammatory responses. In this study, we investigated the role of Nrf2 on the development of EAU. Clinical and pathological examination demonstrated that retinal inflammation was exacerbated in Nrf2 knockout (Nrf2 KO) mice compared to wild type (WT) mice, and the expression of inflammatory cytokines (IFN-γ, IL-6, and IL-17) in the retina was significantly elevated in Nrf2 KO mice. GFAP positive cells (astrocytes) and Iba-1 positive cells (microglia cells) in the retina were more numerous in Nrf2 KO mice compared to WT mice. Furthermore, we examined the suppressive effect of the Nrf2 activator CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline) on the development of EAU. The treatment with CDDO-Im significantly reduced the clinical and pathological score of EAU compared to those of vehicle-treated mice. These findings suggest that Nrf2 plays a regulatory role in the pathogenesis of autoimmune uveoretinitis and the activation of the Nrf2 system may have therapeutic potential for protecting vision from autoimmune neuroinflammation.
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Enfermedades Autoinmunes , Imidazolinas , Uveítis , Animales , Antioxidantes , Autoinmunidad , Citocinas/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Ratones , Ratones Noqueados , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades Neuroinflamatorias , Ácido Oleanólico/análogos & derivados , Proteínas de Unión al Retinol , Uveítis/metabolismoRESUMEN
"Idiopathic" is the most common category of uveitis, representing cases in which a specific diagnosis has not been established despite work-up. Sarcoidosis is a systemic granulomatous disorder affecting multiple organs including the lungs, skin, kidneys, and eyes. We used microRNA (miRNA) microarrays to investigate serum miRNA profiles of patients with ocular sarcoidosis as diagnosed by specific criteria (diagnosed ocular sarcoidosis), and patients with idiopathic uveitis characterized by ocular manifestations of sarcoidosis (suspected ocular sarcoidosis). Principal component analysis (PCA) and hierarchical clustering showed that serum miRNA profiles of diagnosed ocular sarcoidosis and suspected ocular sarcoidosis were both clearly distinguishable from healthy controls. Furthermore, comparative analysis of the miRNA profiles showed highly similar patterns between diagnosed ocular sarcoidosis and suspected ocular sarcoidosis. Pathway analysis revealed common pathways were involved in the two groups, including those of WNT signaling and TGF-beta signaling. Our study demonstrated a high overlap of differentially expressed serum miRNAs in patients with diagnosed ocular sarcoidosis and suspected ocular sarcoidosis, suggesting that these groups share a similar underlying pathology and may represent possible variants of the disease. Characterization of serum miRNA profiles may provide an opportunity for earlier diagnosis and treatment, and may inform more accurate clinical prognosis in patients with an ocular sarcoidosis phenotype.
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Endoftalmitis , MicroARNs , Sarcoidosis , Uveítis , Ojo/patología , Humanos , MicroARNs/genética , Sarcoidosis/diagnóstico , Sarcoidosis/patología , Factor de Crecimiento Transformador beta , Uveítis/diagnóstico , Uveítis/genéticaRESUMEN
OBJECTIVES: Hyper- and hyposensitivity in multiple modalities have been well-documented in subjects with autistic spectrum disorder (ASD) but not in subjects with acquired brain injury (ABI). The purpose of this study was to determine whether subjects with ABI experience altered sensory processing in multiple sensory modalities, and to examine the relationships between impaired sensory processing and the emotional state. METHODS AND PROCEDURES: Sixty-eight patients with brain or spinal cord tumors participated in the study. Cognitive ability and emotional function were tested, and subjective changes were evaluated in two directions (hyper- and hyposensitivity) and five modalities (visual, auditory, tactile, olfactory, and gustatory) at two time points (after disease onset and after surgery). RESULTS: One-fifth of the participants complained of hypersensitivity in the visual domain, and a similar proportion complained of hyposensitivity in the auditory and tactile domains. Additionally, one-third of participants complained of two or more sensory abnormalities after disease onset. A hierarchical regression analysis indicated that auditory and tactile sensory changes predicted a depressive state. CONCLUSION: In conclusion, multimodal sensory changes occurred in patients with brain tumors, manifesting as hyper- or hyposensitivity. Sensory changes might be related to depressive state, but the results were inconclusive.
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Trastorno del Espectro Autista , Neoplasias Encefálicas , Encéfalo , Neoplasias Encefálicas/complicaciones , Humanos , OlfatoRESUMEN
OBJECTIVES: Time awareness may change depending on the mental state or disease conditions, although each individual perceives his/her own sense of time as stable and accurate. Nevertheless, the processes that consolidate altered duration production remain unclear. The present study aimed to manipulate the subjective duration production via memory consolidation through the modulation of neural plasticity. MATERIALS AND METHODS: We first performed false feedback training of duration or length production and examined the period required for natural recovery from the altered production. Next, persistent neural plasticity was promoted by quadripulse transcranial magnetic stimulation (QPS) over the right dorsolateral prefrontal cortex (DLPFC), temporoparietal junction (TPJ), and primary motor cortex (M1). We conducted the same feedback training in the individual and studied how the time course of false learning changed. RESULTS: We observed that altered duration production after false feedback returned to baseline within two hours. Next, immediate exposure to false feedback during neural plasticity enhancement revealed that in individuals who received QPS over the right DLPFC, but not over TPJ or M1, false duration production was maintained for four hours; furthermore, the efficacy persisted for at least one week. CONCLUSION: These findings suggest that, while learned altered duration production decays over several hours, QPS over the right DLPFC enables the consolidation of newly learned duration production.
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Potenciales Evocados Motores , Corteza Motora , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Corteza Prefrontal , Estimulación Magnética TranscranealRESUMEN
OBJECTIVES: Thoracoscopic anatomical single or combined anatomical individual basilar segmentectomy, including subsegmentectomy, is technically challenging due to variations and the deep location of vessels and bronchi in the parenchyma. However, the long-term perioperative outcomes of various anatomical subsegmentectomy approaches have not been reported. Thus, we investigated the effectiveness of thoracoscopic basilar segmentectomy. METHODS: We evaluated the records of 119 patients who underwent thoracoscopic single or complex basilar segmentectomy between January 2005 and December 2020 and compared the fissure and non-fissure approach for S9 and/or S10. RESULTS: A total of 29 patients underwent single segmentectomy, and 90 patients underwent various combined anatomical segmentectomies via video-assisted thoracoscopic surgery and planning using three-dimensional simulation. There were 39 cases of S9 and/or S10 segmentectomy. The median chest tube in-dwell duration and postoperative hospital stay were 1 and 4 days, respectively. The postoperative morbidity (Clavien-Dindo grade II/IIIa) rate was 5.9% without perioperative mortality. Pathological examination revealed 83 cases of lung cancer, 21 cases of metastasis and 15 cases of benign lesions. The postoperative hospitalization duration showed significant differences in the perioperative outcomes between the fissure and non-fissure approaches for S9 and/or S10. CONCLUSIONS: Thoracoscopic anatomical basilar individual segmentectomy has emerged as a safe and feasible procedure. The non-fissure approach enabled anatomic resection of a single segment or combined basal segments, helped avoid dissection of an incomplete fissure and facilitated surgical outcomes similar to the fissure approach.
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Neoplasias Pulmonares , Neumonectomía , Humanos , Tiempo de Internación , Mastectomía Segmentaria , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/métodosRESUMEN
BACKGROUND: Language is a barrier to many patients from refugee backgrounds accessing and receiving quality primary health care. This paper examines the way general practices address these barriers and how this changed following a practice facilitation intervention. METHODS: The OPTIMISE study was a stepped wedge cluster randomised trial set within 31 general practices in three urban regions in Australia with high refugee settlement. It involved a practice facilitation intervention addressing interpreter engagement as one of four core intervention areas. This paper analysed quantitative and qualitative data from the practices and 55 general practitioners from these, collected at baseline and after 6 months during which only those assigned to the early group received the intervention. RESULTS: Many practices (71 %) had at least one GP who spoke a language spoken by recent humanitarian entrants. At baseline, 48 % of practices reported using the government funded Translating and Interpreting Service (TIS). The role of reception staff in assessing and recording the language and interpreter needs of patients was well defined. However, they lacked effective systems to share the information with clinicians. After the intervention, the number of practices using the TIS increased. However, family members and friends continued to be used to interpret with GPs reporting patients preferred this approach. The extra time required to arrange and use interpreting services remained a major barrier. CONCLUSIONS: In this study a whole of practice facilitation intervention resulted in improvements in procedures for and engagement of interpreters. However, there were barriers such as the extra time required, and family members continued to be used. Based on these findings, further effort is needed to reduce the administrative burden and GP's opportunity cost needed to engage interpreters, to provide training for all staff on when and how to work with interpreters and discuss and respond to patient concerns about interpreting services.
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Medicina General , Refugiados , Australia , Barreras de Comunicación , Humanos , TraducciónRESUMEN
OBJECTIVES: To examine whether primary care outreach facilitation improves the quality of care for general practice patients from refugee backgrounds. DESIGN: Pragmatic, cluster randomised controlled trial, with stepped wedge allocation to early or late intervention groups. SETTING, PARTICIPANTS: 31 general practices in three metropolitan areas of Sydney and Melbourne with high levels of refugee resettlement, November 2017 - August 2019. INTERVENTION: Trained facilitators made three visits to practices over six months, using structured action plans to help practice teams optimise routines of refugee care. MAJOR OUTCOME MEASURE: Change in proportion of patients from refugee backgrounds with documented health assessments (Medicare billing). Secondary outcomes were refugee status recording, interpreter use, and clinician-perceived difficulty in referring patients to appropriate dental, social, settlement, and mental health services. RESULTS: Our sample comprised 14 633 patients. The intervention was associated with an increase in the proportion of patients with Medicare-billed health assessments during the preceding six months, from 19.1% (95% CI, 18.6-19.5%) to 27.3% (95% CI, 26.7-27.9%; odds ratio, 1.88; 95% CI, 1.42-2.50). The impact of the intervention was greater in smaller practices, practices with larger proportions of patients from refugee backgrounds, recent training in refugee health care, or higher baseline provision of health assessments for such patients. There was no impact on refugee status recording, interpreter use increased modestly, and reported difficulties in refugee-specific referrals to social, settlement and dental services were reduced. CONCLUSIONS: Low intensity practice facilitation may improve some aspects of primary care for people from refugee backgrounds. Facilitators employed by local health services could support integrated approaches to enhancing the quality of primary care for this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001970235 (retrospective).
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Atención a la Salud/organización & administración , Atención Primaria de Salud/organización & administración , Mejoramiento de la Calidad/organización & administración , Refugiados , Instituciones de Atención Ambulatoria , Australia , Humanos , Derivación y ConsultaRESUMEN
SET-Nup214 is a recurrent fusion gene that is mainly observed in T-cell acute lymphoblastic leukemia (T-ALL). Dysregulation of homeobox (Hox) genes is frequently observed in patients with leukemia. Consistent with this, HoxA genes are upregulated in the SET-Nup214 + T-ALL cell line and patients. Although SET-Nup214 has been reported to be recruited to the promoter regions of HoxA genes, the detailed mechanisms of how SET-Nup214 specifically binds to HoxA gene promoters and regulates HoxA gene expression are not known. In this study, we demonstrated that SET-Nup214 interacts with MLL via the SET acidic region of SET-Nup214. SET-Nup214 and MLL cooperatively enhance the promoter activity of the HoxA10 gene. Neither the SET region alone nor the Nup214 region alone sufficiently enhanced the HoxA10 gene promoter. Our results indicated that the SET portion of the SET-Nup214-fusion protein is important for interactions with MLL and transcription enhancement of the HoxA10 gene. Thus, our study will contribute to the understanding of how SET-Nup214 and MLL disturb the expression of HoxA10 gene in leukemia.
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Proteínas de Unión al ADN/metabolismo , Chaperonas de Histonas/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Leucemia , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Complejo Poro Nuclear , Proteínas de Unión al ADN/genética , Expresión Génica , Chaperonas de Histonas/genética , Proteínas Homeobox A10 , Humanos , Proteínas de Complejo Poro Nuclear/metabolismo , Regiones Promotoras GenéticasRESUMEN
Massive ovarian edema (MOE) is a rare non-neoplastic clinicopathologic disease that is characterized by stromal edema and is caused by the partial or intermittent obstruction of venous and lymphatic drainage. The literature on MOE contains approximately 200 cases, but only 12 cases of MOE during pregnancy have been reported to date. We report a case of MOE at 22 weeks of gestation that was diagnosed preoperatively, and the patient underwent laparoscopic surgery. Accurate preoperative diagnosis of MOE is important because it enables the selection of a therapeutic option, such as fundamental surgery, including adnexectomy; conservative surgery, including the release of torsion and ovarian biopsy; and conservative treatment without surgery. MOE should be considered as a differential diagnosis for an enlarged ovary during pregnancy. Laparoscopic surgery may be a useful therapeutic option for MOE, especially during pregnancy.
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Nucleoli are sites where both the large and small ribosomal subunits mature. Biochemical assays have suggested that a multivalent nucleolar protein, NPM1/nucleophosmin contributes to the formation of the outer layer of the nucleolus. Prior works show that NPM1 depletion disorganizes the nucleolar structure. However, the mechanism of how NPM1 regulates the nucleolar structure has been unknown. We demonstrated that NPM1 directly interacts with the large ribosomal subunits and maintains them in the nucleolus. Ectopically localized NPM1 efficiently recruits only the large ribosomal subunit precursors, while ectopically localized large ribosomal subunit by the ribosomal protein RPL4 efficiently recruits NPM1. These results suggest that the nucleolar localization of NPM1 and the large ribosomal subunit precursors are mutually dependent. Furthermore, proteomic and localization analyses suggest that NPM1 plays a crucial role in the accumulation of the late processing machinery of the large ribosomal subunits in the nucleolus. Our results suggest that NPM1 maintains the pre-ribosomes and assembly machinery in the nucleolus, which in turn determines the nucleolar volume.
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Nucléolo Celular/genética , Proteínas Nucleares/genética , Proteínas Ribosómicas/genética , Ribosomas/genética , Genes de ARNr/genética , Nucleofosmina , Unión Proteica/genética , Proteómica/métodos , Subunidades Ribosómicas Grandes/genéticaRESUMEN
Nucleolin (NCL) is a nucleolar protein i.e. involved in the regulation of the nucleolar structure and functions, and consists of three distinct regions: the N-terminal region; the middle region, which contains four RNA-recognition motifs (RRMs); and the C-terminal glycine- and arginine-rich (GAR) region. The primary function of the RRMs and GAR is thought to be specific RNA binding. However, it is not well understood how these RNA-binding regions of NCL separately or cooperatively regulate its nucleolar localization and functions. To address this issue, we constructed mutant proteins carrying point mutations at the four RRMs individually or deletion of the C-terminal GAR region. We found that the GAR deletion and the mutations in the fourth RRM (RRM4) decreased the nucleolar localization of NCL. Biochemical analyses showed that NCL interacted directly with ribosomal RNAs (rRNAs) and G-rich oligonucleotides, and that this interaction was decreased by mutations at RRM1 and RRM4 and GAR deletion. Although GAR deletion decreased the rRNA-binding activity of NCL, the mutant was efficiently coprecipitated with rRNAs and nucleolar proteins from cell extracts. These contradictory results suggest that NCL stably localizes to the nucleoli via the interactions with rRNAs and nucleolar proteins via GAR, RRM1 and RRM4.
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Arginina/metabolismo , Nucléolo Celular/metabolismo , Glicina/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Motivos de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Secuencia de Aminoácidos/genética , Arginina/genética , Glicina/genética , Células HeLa , Humanos , Proteínas Nucleares/genética , Fosfoproteínas/genética , Mutación Puntual , Transporte de Proteínas , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Proteínas de Unión al ARN/genética , NucleolinaRESUMEN
Lesion studies have shown that the right temporal lobe is crucial for recognition of facial expressions, particularly fear expressions. However, in previous studies, premorbid abilities of the patients were unknown and the effects of epileptic discharge could not be excluded. Herein, we report a case of a patient who underwent assessments of facial recognition before and after brain surgery and exhibited biased recognition of facial expressions. The patient was a 29-year-old right-handed male who underwent an awake craniotomy. Compared with the preoperative assessment, after the surgery, he showed biased recognition of surprised facial expressions, and his ability to recognize other facial expressions either improved or remained unchanged. These findings support the idea that the right temporal lobe is crucial for the recognition of facial expressions of surprise and that functional connectivity between various brain regions plays an important role in the ability to recognize facial expressions.
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BACKGROUND: Australia is one of many nations struggling with the challenges of delivering quality primary health care (PHC) to increasing numbers of refugees. The OPTIMISE project represents a collaboration between 12 organisations to generate a model of integrated refugee PHC suitable for uptake throughout Australia. This paper describes the methodology of one component; an outreach practice facilitation intervention, directed towards improving the quality of PHC received by refugees in Australian general practices. METHODS: Our mixed methods study will use a cluster stepped wedge randomised controlled trial design set in 3 urban regions of high refugee resettlement in Australia. The intervention was build upon regional partnerships of policy advisors, clinicians, academics and health service managers. Following a regional needs assessment, the partnerships reached consensus on four core areas for intervention in general practice (GP): recording of refugee status; using interpreters; conducting comprehensive health assessments; and referring to refugee specialised services. Refugee health staff trained in outreach practice facilitation techniques will work with GP clinics to modify practice routines relating to the four core areas. 36 general practice clinics with no prior involvement in a refugee health focused practice facilitation will be randomly allocated into early and late intervention groups. The primary outcome will be changes in number of claims for Medical Benefit Service reimbursed comprehensive health assessments among patients identified as being from a refugee background. Changes in practice performance for this and 3 secondary outcomes will be evaluated using multilevel mixed effects models. Baseline data collection will comprise (i) pre-intervention provider survey; (ii) two surveys documenting each practices' structure and approaches to delivery of care to refugees. De-identified medical record data will be collected at baseline, at the end of the intervention and 6 and 12 months following completion. DISCUSSION: OPTIMISE will test whether a regionally oriented practice facilitation initiative can improve the quality of PHC delivered to refugees. Findings have the potential to influence policy and practice in broader primary care settings. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001970235 , 05/12/2018, Retrospectively registered. Protocol Version 1, 21/08/2017.
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Atención a la Salud/organización & administración , Atención Primaria de Salud/organización & administración , Mejoramiento de la Calidad/organización & administración , Refugiados , Instituciones de Atención Ambulatoria , Australia , Humanos , Derivación y ConsultaRESUMEN
IL-12 is a key cytokine for the promotion of CD4+ T cells differentiation to type 1 helper T cells. IL-12 is a heterodimer (IL-12p70) consisting of p40 and p35 subunits, and is mainly secreted from activated antigen-presenting cells, such as macrophages and dendritic cells (DCs). In this study, we found that activated mouse bone marrow-derived DCs (BMDCs) produced a p40 splice variant form mRNA in addition to the conventional p40 mRNA. This p40 variant mRNA was produced by alternative splicing in exon 5, and possessed a premature stop codon. As a result, the p40 variant protein contained 157 amino acids of the N-terminal part of p40 and an additional 10 novel amino acids. When the p40 variant was expressed in HEK-293T cells, it was not secreted from the cells. To investigate the function of the p40 variant, it was co-expressed with p40 and/or p35. The p40 variant did not affect the secretion of IL-12p40 or IL-12p70, or the function of the secreted p70. In contrast, the secretion of IL-12p80, a homodimeric IL-12 with two p40 subunits, was significantly decreased when the p40 variant was expressed. This new splicing variant p40 may act to fine-tune the function of IL-12p80.
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Empalme Alternativo/genética , Subunidad p40 de la Interleucina-12/genética , Interleucina-12/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Exones/genética , Células HEK293 , Humanos , Interleucina-12/química , Subunidad p40 de la Interleucina-12/química , Cinética , Ratones Endogámicos C57BL , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT4/metabolismoRESUMEN
BACKGROUND: Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This retrospective multicenter study evaluated the efficacy and safety of released washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs were prepared by washing leukoreduced apheresis PCs with the platelet additive solution, BRS-A, using automated cell processors. RESULTS: Clinical data were obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were used in 94.5% of the patients with a history of recurrent or severe transfusion reactions for preventing such reactions. Responses of RWPCs were evaluated as complete response (91.6%), partial response (8.2%), no-change (0.2%), and progression (0%) and overall response was equal across subgroups divided by patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post-transfusion were 13.5 (range, 1.9-35.4) × 109/L and 3.5 (range, -13 to 53.6) × 109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) × 109/L in patients without risk factors associated with platelet transfusion refractoriness. Transfusion reactions to RWPCs were observed in only nine transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This study demonstrated that RWPCs were effective and safe in patients with a history of transfusion reactions. Further prospective studies on efficacy together with cost-benefit analysis in RWPCs are needed.