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AIM(S): To synthesize aged care provider, resident and residents' family members' perspectives and experiences of medication administration in aged care facilities; to determine the incidence of medication administration errors, and the impact of medication administration on quality of care and resident-centredness in aged care facilities. DESIGN: A mixed-methods systematic review. PROSPERO ID: CRD42023426990. DATA SOURCES: The AMED, CINAHL, MEDLINE, EMBASE, EMCARE, PsycINFO, Scopus and Web of Science core collection databases were searched in June 2023. REVIEW METHODS: Included studies were independently screened, selected and appraised by two researchers. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was followed, with the Mixed Methods Appraisal Tool was used for critical appraisal. Convergent synthesis of data, thematic synthesis and meta-analysis were performed. RESULTS: One hundred and twenty-eight studies were included (33 qualitative, 85 quantitative and 10 mixed-methods). Five themes were formulated, including 1) Staffing concerns, 2) The uncertain role of residents, 3) Medication-related decision-making, 4) Use of electronic medication administration records and 5) Medication administration errors. Educational interventions for aged care workers significantly reduced medication administration errors, examined across five studies (OR = 0.37, 95%CI 0.28-0.50, p < .001). CONCLUSIONS: Medication administration in aged care facilities is challenging and complex on clinical and interpersonal levels. Clinical processes, medication errors and safety remain focal points for practice. However, more active consideration of residents' autonomy and input by aged care workers and providers is needed to address medication administration's interpersonal and psychosocial aspects. New directions for future research should examine the decision-making behind dose form modification, aged care workers' definitions of medication omission and practical methods to support residents' and their family members' engagement during medication administration. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: It is important that medication administration in aged care facilities be more clearly acknowledged as both a clinical and interpersonal task. More attention is warranted regarding aged care workers clinical decision-making, particularly concerning dose form modification, covert administration and medication omissions. Resident-centred care approaches that support resident and family engagement around medication administration may improve adherence, satisfaction and quality of care. IMPACT: What Problem Did the Study Address? Medication administration in aged care facilities is a complex clinical and interpersonal activity. Still, to date, no attempts have been made to synthesize qualitative and quantitative evidence around this practice. There is a need to establish what evidence exists around the perspectives and experiences of aged care workers, residents and resident's family members to understand the challenges, interpersonal opportunities and risks during medication administration. What Were the Main Findings? There is a lack of empirical evidence around resident-centred care approaches to medication administration, and how residents and their families could be enabled to have more input. Dose form modification occurred overtly and covertly as part of medication administration, not just as a method for older adults with swallowing difficulties, but to enforce adherence with prescribed medications. Medication administration errors typically included medication omission as a category of error, despite some omissions stemming from a clear rationale for medication omission and resident input. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: The findings of this systematic review contribute to aged care policy and practice regarding medication administration and engagement with older adults. This review presents findings that provide a starting point for aged care workers in regards to professional development and reflection on practice, particularly around clinical decision-making on dose form modification, medication administration errors and the tension on enabling resident input into medication administration. For researchers, this review highlights the need to develop resident-centred care approaches and interventions, and to assess whether these can positively impact medication administration, resident engagement, adherence with prescribed medications and quality of care. REPORTING METHOD: This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Page et al., 2021). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution to this systematic review.
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AIM: To explore the experiences and perceptions of communication about managing medication across transitions of care for residents living in aged care homes and their family caregivers. BACKGROUND: Effective medication communication across transitions of care involves exchanging information, resident, and family caregiver's participation in decision-making, and shared responsibility. DESIGN: A qualitative meta-synthesis. METHOD: This review was conducted in accordance with the PRISMA 2020 guidelines and the accompanying 27-item checklist. A systematic search of seven electronic databases (Embase, PsycINFO, Medline Ovid, Scopus, CINAHL, EmCare and Web of Science) was performed from inception to December 2023. Studies eligible for inclusion in this review were required to be published in peer-reviewed English journals and focus on medication communication among healthcare providers, residents and family caregivers during transitions of care for aged care residents. The JBI Critical Appraisal Checklist for Qualitative Research was employed for the critical appraisal of the studies, and the COREQ checklist was used to evaluate their quality. RESULTS: Of the 2610 studies identified, 12 met the inclusion criteria. No study was excluded based on quality. Two main themes were generated: (1) Medication information exchange involving residents and families, and (2) resident and family factors influencing medication communication engagement. The findings revealed a lack of supportive structure for effective communication and collaboration among residents, family caregivers and healthcare providers during transitions of care, marked by one-way interactions and limited evidence of shared decision-making or family caregiver engagement in medication management communication, despite varying individual needs and preferences. CONCLUSIONS: Communication about medication management during transitions of care focused on sharing details rather than active engagement. Residents and their family caregivers have individual needs and perspectives regarding communication about medication management, which are not well addressed by healthcare providers during transitions of care. Healthcare providers' communication remains limited, and family caregivers are underutilised.
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OBJECTIVE: The purpose of this thematic review is to examine the literature on the publics' preferences of scarce medical resource allocation during COVID-19. STUDY DESIGN: Literature review. METHODS: A review of Ovid MEDLINE, Embase, CINAHL and Scopus was performed between December 2019 and June 2022 for eligible articles. RESULTS: Fifteen studies using three methodologies and spanning five continents were included. Five key themes were identified: (1) prioritise the youngest; (2) save the most lives; (3) egalitarian allocation approaches; (4) prioritise healthcare workers; and (5) bias against particular groups. The public gave high priority to allocation that saved the most lives, particularly to patients who are younger and healthcare workers. Themes present but not supported as broadly were giving priority to individuals with disabilities, high frailty or those with behaviours that may have contributed to their ill-health (e.g. smokers). Allocation involving egalitarian approaches received the least support among community members. CONCLUSION: The general public prefer rationing scarce medical resources in the COVID-19 pandemic based on saving the most lives and giving priority to the youngest and frontline healthcare workers rather than giving preference to patients with disabilities, frailty or perceived behaviours that may have contributed to their own ill-health. There is also little public support for allocation based on egalitarian strategies.
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COVID-19 , Fragilidad , Atención a la Salud , Asignación de Recursos para la Atención de Salud , Personal de Salud , Humanos , PandemiasRESUMEN
BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but the objective assessment of patient compliance with self-management recommendations has seldom been studied. OBJECTIVE: This study aimed to evaluate patient compliance with self-management recommendations of an innovative telemonitoring enhanced care program for CHF (ITEC-CHF). METHODS: We conducted a multicenter randomized controlled trial with a 6-month follow-up. The ITEC-CHF program comprised the provision of Bluetooth-enabled scales linked to a call center and nurse care services to assist participants with weight monitoring compliance. Compliance was defined a priori as weighing at least 4 days per week, analyzed objectively from weight recordings on the scales. The intention-to-treat principle was used to perform the analysis. RESULTS: A total of 184 participants (141/184, 76.6% male), with a mean age of 70.1 (SD 12.3) years, were randomized to receive either ITEC-CHF (n=91) or usual care (control; n=93), of which 67 ITEC-CHF and 81 control participants completed the intervention. For the compliance criterion of weighing at least 4 days per week, the proportion of compliant participants in the ITEC-CHF group was not significantly higher than that in the control group (ITEC-CHF: 67/91, 74% vs control: 56/91, 60%; P=.06). However, the proportion of ITEC-CHF participants achieving the stricter compliance standard of at least 6 days a week was significantly higher than that in the control group (ITEC-CHF: 41/91, 45% vs control: 23/93, 25%; P=.005). CONCLUSIONS: ITEC-CHF improved participant compliance with weight monitoring, although the withdrawal rate was high. Telemonitoring is a promising method for supporting both patients and clinicians in the management of CHF. However, further refinements are required to optimize this model of care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.
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Insuficiencia Cardíaca/terapia , Cooperación del Paciente/estadística & datos numéricos , Consulta Remota/métodos , Telemedicina/métodos , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Automanejo , Resultado del TratamientoRESUMEN
BACKGROUND: Refugees are potentially at an increased risk for health problems due to their past and current migration experiences. How migration factors shape refugee health is not well understood. We examined the association between migration factors and the self-rated general health of adult humanitarian refugees living in Australia. METHODS: We analyzed the first three waves of data from the 'Building A New Life In Australia' longitudinal survey of 2399 humanitarian refugees resettled in Australia. The study outcome was self-rated health measured by the 36-Item Short Form Health Survey. Predictors were migration process and resettlement factors. We used generalized linear mixed models to investigate the relationship between predictor and outcome variables. RESULTS: Poor general health persisted among this refugee population at high levels throughout the three-year follow-up. At baseline, 35.7% (95% CI: 33.8-37.7%) of the study population reported poorer general health. Female gender, increasing age and post-migration financial stressors were positively associated with poorer general health. Having a university degree and absence of chronic health conditions were seemingly protective against declining general health (OR: 0.50; 95% CI: 0.65-1.81 and OR: 0.15, 95% CI: 0.09-1.04, respectively). CONCLUSION: Our results show that there is persisting high prevalence of poorer general health among adult refugees across the initial years of resettlement in Australia. This finding suggests unmet health needs which may be compounded by the challenges of resettlement in a new society, highlighting the need for increased clinical awareness of this sustained health burden to help inform and prepare refugee health care and settlement service providers.
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Emigrantes e Inmigrantes , Emigración e Inmigración , Estado de Salud , Refugiados , Adolescente , Adulto , Factores de Edad , Anciano , Altruismo , Australia/epidemiología , Enfermedad Crónica , Estudios de Cohortes , Autoevaluación Diagnóstica , Escolaridad , Femenino , Encuestas Epidemiológicas , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Refugiados/estadística & datos numéricos , Factores Sexuales , Adulto JovenRESUMEN
BACKGROUND: Refugees are one of the most vulnerable groups in our society. They are at risk of poor physical and mental health outcomes, much of this attributed to traumatic events prior to migration and the additional risk factors refugees face in the host nations. However, how migration factors shape the health of resettling refugees is not well understood. This study uses a mixed methods approach to examine how pre- and post-migration factors shape the self-rated health of resettling adult refugees in an effort to address the current knowledge gap. METHODS: This study will use a sequential explanatory mixed method study design. We begin by analyzing resettlement and health data from the 'Building a New Life In Australia' longitudinal study of humanitarian refugees resettled in Australia to identify significant associations between migration factors and refugee health. Then, a series of semi-structured interviews with resettled refugees will further explore the lived experiences of refugees with respect to the relationship between migration and refugee health. Finally, we will integrate both sets of findings to develop a detailed understanding of how and why migratory factors contribute to refugee health during resettlement. DISCUSSION: There is a paucity of studies that examine the multidimensional nature of refugee health during resettlement and as a result, little is understood about their resettlement health needs. This information is required to inform existing or new resettlement interventions to help promote or improve refugee health. To overcome these limitations in the research knowledge, this study will use a mixture of study methods to illustrate the complex and multifaceted determinants of refugee health during resettlement in Australia.
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Autoevaluación Diagnóstica , Emigración e Inmigración/tendencias , Refugiados/psicología , Adulto , Australia , Femenino , Estado de Salud , Humanos , Entrevistas como Asunto , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND: The health status of refugees is a significant factor in determining their success in resettlement and relies heavily on self-rated measures of refugee health. The selection of robust and appropriate self-rated health measurement tools is challenging due to the number and methodological variation in the use of assessment tools across refugee health studies. This study describes the existing self-report health measures which have been used in studies of adult refugees living in the community to allow us to address the challenges of selecting appropriate assessments to measure health within refugee groups. METHODS: Electronic databases of Ovid Medline, CINAHL, SCOPUS, Embase and Scopus. RESULTS: This review identified 45 different self-rated health measurements in 183 studies. Most of the studies were cross sectional explorations of the mental health status of refugees living in community settings within Western nations. A third of the tools were designed specifically for use within refugee populations. More than half of the identified measurement tools have been evaluated for reliability and/or validity within refugee populations. Much variation was found in the selection, development and testing of measurement tools across the reviewed studies. CONCLUSION: This review shows that there are currently a number of reliable and valid tools available for use in refugee health research; however, further work is required to achieve consistency in the quality and in the use of these tools. Methodological guidelines are required to assist researchers and clinicians in the development and testing of self-rated health measurement tools for use in refugee research.
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Autoevaluación Diagnóstica , Estado de Salud , Encuestas Epidemiológicas , Refugiados , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Salud Mental/etnología , Refugiados/psicología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN. RESULTS: ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age. CONCLUSION: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.
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Albuminuria/etnología , Peso al Nacer , Índice de Masa Corporal , Glomerulonefritis/complicaciones , Nativos de Hawái y Otras Islas del Pacífico , Insuficiencia Renal/complicaciones , Infecciones Estreptocócicas/complicaciones , Adolescente , Adulto , Albuminuria/diagnóstico , Albuminuria/etiología , Australia/epidemiología , Femenino , Glomerulonefritis/etnología , Humanos , Incidencia , Recién Nacido de Bajo Peso , Masculino , Insuficiencia Renal/etnología , Factores de Riesgo , Infecciones Estreptocócicas/etnología , Adulto JovenRESUMEN
BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a "multihit" model of albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary albumin/creatinine ratios (ACR) were measured in all subjects who volunteered to participate in a community-wide health screen. Subjects for this study were young adults who had birth weights recorded and whose medical records were inspected for a history of post-streptococcal glomerulonephritis (PSGN). Urine ACR levels were evaluated in the context of birth weights, PSGN history and current BMI. RESULTS: 580 subjects (335 males and 245 females) who were aged 18 - 39 years at time of screening and qualified for inclusion. 26% of subjects had birth weights of < 2.5 kg, and the median birth weight was 2.8 kg. 23% of subjects had a remote history of PSGN, all 3 or more years earlier. Median BMI for the group was 21 kg/m2. Urine ACR levels exceeded the microalbuminuria threshold of 3.4 g/mol in 35.5% of subjects. Birth weight (inversely), remote PSGN, and current BMI were all independent predictors of ACR levels. Median levels of ACR were lowest in those with birth weights ≥ 2.5 kg, and no history of PSGN, intermediate in those with either birth weights < 2.5 kg or a history of PSGN, and highest in those with both low birth weights and a PSGN history. ACR levels were higher in those with BMIs above the median values, most notably in those with lower birth weights or a PSGN history or both. INTERPRETATION: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, low birth weight and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age, and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.
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Albuminuria/etnología , Peso al Nacer , Índice de Masa Corporal , Glomerulonefritis/etnología , Nativos de Hawái y Otras Islas del Pacífico , Adolescente , Adulto , Australia/epidemiología , Femenino , Glomerulonefritis/etiología , Humanos , Incidencia , Enfermedades Renales/complicaciones , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden.
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Glomerulonefritis/etnología , Enfermedades Renales/etnología , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Escabiosis/etnología , Enfermedades Cutáneas Bacterianas/etnología , Infecciones Estreptocócicas/etnología , Enfermedad Aguda , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Albuminuria/epidemiología , Australia , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Niño , Preescolar , Enfermedad Crónica , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis/diagnóstico , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Enfermedades Renales/diagnóstico , Modelos Logísticos , Masculino , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Escabiosis/diagnóstico , Distribución por Sexo , Factores Sexuales , Enfermedades Cutáneas Bacterianas/diagnóstico , Infecciones Estreptocócicas/diagnóstico , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but little is known about the usability and patients' willingness to engage with this technology. OBJECTIVE: This study aims to evaluate feedback from patients with CHF following participation in the Innovative Telemonitoring Enhanced Care program for CHF (ITEC-CHF) study. METHODS: The telemonitoring intervention consisted of three components: remote weight monitoring, structured telephone support, and nurse-led collaborative care. Participants were provided with electronic weighing scales (W550; ForaCare), and a computer tablet (Galaxy Tab A; Samsung). They were asked to weigh themselves on the provided scales daily. Telemonitoring was integrated with a personal assistance call service and a nurse care service according to their workflows in usual care. Feedback on the usability of ITEC-CHF was collected via survey from study participants following 6 months of receiving telemonitoring care for their body weight. Survey responses were provided on a 5-point Likert scale and through open-ended questions to determine participants' perceived benefits and barriers to using ITEC-CHF. RESULTS: A total of 67 participants (49/67, 73% male), with a mean age of 69.8 (SD 12.4) years completed the survey. The majority of participants agreed or strongly agreed that the ITEC-CHF program was easy to use (61/67, 91%), easy to navigate (51/65, 78%), useful (59/65, 91%), and made them feel more confident in managing their weight (57/67, 85%). Themes related to participants' perceptions of telemonitoring included increased support for early intervention of clinical deterioration, improved compliance to daily weighing, a sense of reassurance, and improved self-care and accountability, among others. CONCLUSIONS: ITEC-CHF was rated highly on usability and was well accepted by users as part of their routine self-management activities. Participants were willing to use telemonitoring because they perceived a broad spectrum of benefits for CHF management. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ID ACTRN 12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.
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INTRODUCTION: Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients' compliance, and associated health and economic outcomes. METHODS AND ANALYSIS: An open multicentre randomised controlled trial has been designed. Patients will be recruited and randomised to receive either ITEC-CHF (n=150) or usual care CHF (n=150) for at least 6 months. ITEC-CHF combines usual care and an additional telemonitoring service including remote weight monitoring, structured telephone support and nurse-led collaborative care. The primary outcomes are the compliance rates with the best-practice guidelines for daily weight monitoring. The secondary outcomes include the compliance with other guideline recommendations (health maintenance, medication, diet and exercise), health (health-related quality of life, risk factors, functional capacity and psychological states) and economic outcomes related to the use of healthcare resources such as hospital readmissions and general practitioner/emergency department visits. ETHICS AND DISSEMINATION: The clinical trial has been approved by Peninsula Health Human Research Ethics Committee (HREC Reference: HREC/14/PH/27), Royal Perth Hospital Human Research Ethics Committee (Reference: 15-081) and the Curtin University Human Research Ethics Committee (Reference: HR 181/2014). We will disseminate the final results to the public via conferences and journal publications. A final study report will also be provided to the ethics committees. TRIAL REGISTRATION NUMBER: Registered with Australian New Zealand Clinical Trial Registry (ACTRN12614000916640).
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Adhesión a Directriz , Insuficiencia Cardíaca/terapia , Cooperación del Paciente , Autocuidado/métodos , Telemedicina/métodos , Enfermedad Crónica/terapia , Protocolos Clínicos , Humanos , Calidad de Vida , Factores de Riesgo , TeléfonoRESUMEN
To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10(-800)), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes ANTXR2 (rs4333130; P = 9.3 x 10(-8)) and IL1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 x 10(-14)) and ERAP1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.
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Sitios Genéticos/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Complejo Mayor de Histocompatibilidad/genética , Espondilitis Anquilosante/genética , Estudios de Cohortes , Humanos , Polimorfismo de Nucleótido Simple/genética , Reproducibilidad de los ResultadosRESUMEN
UNLABELLED: Using a moderate-sized cohort selected with extreme BMD (n = 344; absolute value BMD, 1.5-4.0), significant association of several members of the Wnt signaling pathway with bone densitometry measures was shown. This confirms that extreme truncate selection is a powerful design for quantitative trait association studies of bone phenotypes. INTRODUCTION: Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate-sized extreme truncate selected cohort (absolute value BMD Z-scores = 1.5-4.0; n = 344). MATERIALS AND METHODS: Ninety-six tag-single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r(2) > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty-four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane-Armitage test for dichotomous variables or by linear regression for quantitative traits. RESULTS: Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. CONCLUSIONS: This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome-wide studies of quantitative bone phenotypes relevant to osteoporosis.