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1.
ESMO Open ; 8(6): 102043, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951130

RESUMO

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC), has altered the treatment landscape in breast cancer (BC), irrespective of the HR-receptor status. The use of the agent is increasing, despite the finding that exposure to T-DXd increases the risk of interstitial lung disease (ILD), particularly in BC patients. Although T-DXd-related ILD can be potentially severe and life-threatening, most low-grade cases can be treated safely using a multidisciplinary approach comprising early and accurate diagnosis, effective management, close monitoring, and the prompt administration of steroids. Additionally, increasing patients' education on ILD symptoms ensures close attention and enables prompt reporting, enhancing patient outcomes. It is recommended that predictive biomarkers are assessed in patients with risk factors for developing ILD. Currently, diagnostic criteria comprise newly identified pulmonary opacities, the relation of symptom onset to medication initiation, and the exclusion of other causes of ILD. The general condition of patients is weakened during the management of ILD (BC progression and corticosteroid treatment). Consequently, BC chemotherapy might be attenuated. This highlights the importance of preventing (high-grade) ILD, especially since its use is expanded. Identifying high-risk patients, diagnosing, and customizing treatment is, however, challenging and additional information on patient selection is often not fully clarified. In this paper, we provide updated multidisciplinary clinical guidance for patient selection, proactive monitoring, early diagnosis, and effectively management of T-DXd-induced ILD in HER2-positive BC patients. We describe the risk factors for developing ILD, patients' characteristics of ILD, and the histopathological and radiographic characteristics of ILD, including real-world clinical practice reports. These recommendations provide a structured step-by-step approach for managing each suspected BC-related ILD grade.


Assuntos
Neoplasias da Mama , Imunoconjugados , Doenças Pulmonares Intersticiais , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Detecção Precoce de Câncer , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia
2.
East Asian Arch Psychiatry ; 33(2): 37-43, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37400226

RESUMO

INTRODUCTION: Community treatment orders (CTOs) enable patients to actively engage in mental health services while being supervised in the community outside the hospital setting. However, the efficacy of CTOs remains controversial in terms of mental health services usage or service contacts, emergency visits, and violence. METHODS: The databases PsychINFO, Embase, and Medline were searched on 11 March 2022 by 2 independent reviewers through the Covidence website (www.covidence.org). Randomised or non-randomised case-control studies and pre-post studies were included if they examine the effect of CTOs on service contacts, emergency visits, and violence in individuals with mental illnesses by comparing with control groups or pre-CTO conditions. Conflicts were resolved by consultation of the third independent reviewer. RESULTS: Sixteen studies provided sufficient data in the target outcome measures and were included in analysis. Variability in the risk of bias was high among studies. Meta-analyses were conducted separately for case-control studies and pre-post studies. For service contacts, a total of 11 studies with 66,192 patients reported changes in the number of service contacts under CTOs. In 6 case-control studies, a small non-significant increase in service contacts was observed in those under CTOs (Hedge's g = 0.241, z = 1.535, p = 0.13). In 5 pre-post studies, a large and significant increase in service contacts was noted after CTOs (Hedge's g = 0.830, z = 5.056, p < 0.001). For emergency visits, a total of 6 studies with 930 patients reported changes in the number of emergency visits under CTOs. In 2 case-control studies, a small non-significant increase in emergency visits was noted in those under CTOs (Hedge's g = -0.196, z = -1.567, p = 0.117). In 4 pre-post studies, a small significant decrease in emergency visits was noted after CTOs (Hedge's g = 0.553, z = 3.101, p = 0.002). For violence, a total of 2 pre-post studies reported a moderate significant reduction in violence after CTOs (Hedge's g = 0.482, z = 5.173, p < 0.001). CONCLUSION: Case-control studies showed inconclusive evidence, but pre-post studies showed significant effects of CTOs in promoting service contacts and reducing emergency visits and violence. Future studies on cost-effectiveness analysis and qualitative analysis for specific populations with various cultures and backgrounds are warranted.


Assuntos
Serviços Comunitários de Saúde Mental , Transtornos Mentais , Serviços de Saúde Mental , Humanos , Transtornos Mentais/terapia , Violência/prevenção & controle , Serviço Hospitalar de Emergência
3.
Domest Anim Endocrinol ; 83: 106787, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36863302

RESUMO

Irisin is a 112 amino acid peptide hormone cleaved from the fibronectin type III domain-containing protein. Irisin is highly conserved across vertebrates, suggesting evolutionarily conserved common functions among domestic animals. These functions include the browning of white adipose tissue and increased energy expenditure. Irisin has been detected and studied primarily in plasma, serum, and skeletal muscle, but has also been found in adipose tissue, liver, kidney, lungs, cerebrospinal fluid, breast milk, and saliva. This wider tissue presence of irisin suggests additional functions beyond its role as a myokine in regulating energy use. We are beginning to understand irisin in domestic animals. The goal of this review is to provide an up-to-date commentary on irisin structure, tissue distribution, and functions across vertebrates, especially mammals of importance in veterinary medicine. Irisin could be explored as a potential candidate for developing therapeutic agents and biomarkers in domestic animal endocrinology.


Assuntos
Animais Domésticos , Fibronectinas , Animais , Fibronectinas/metabolismo , Tecido Adiposo/metabolismo , Músculo Esquelético/metabolismo , Biomarcadores , Mamíferos/metabolismo
4.
Eur Rev Med Pharmacol Sci ; 26(10): 3585-3592, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35647840

RESUMO

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.


Assuntos
Desenvolvimento Fetal , Neoplasias , Peso ao Nascer , Carcinogênese , Epigenômica , Feminino , Desenvolvimento Fetal/genética , Humanos , Recém-Nascido , Neoplasias/genética , Gravidez
5.
J Endocrinol Invest ; 45(10): 1909-1918, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35751804

RESUMO

PURPOSE: Hypoparathyroidism (HypoPT) is a rare endocrine disease and conventional therapy is based on calcium and vitamin D analogues. Conventional therapy does not restore calcium homeostasis and patients complain with neuropsychological symptoms, which have been evaluated with nonspecific self-administered questionnaires. This study aims to evaluate cognitive functions of patients with chronic post-surgical (PS)-HypoPT compared to a control population, using a standardized neuropsychological approach and evaluating the relationship with serum calcium (Alb-Ca). METHODS: Observational, monocentric study on 33 patients with PS-HypoPT and 24 controls, in whom biochemical testing and a standardized neuropsychological assessment by a trained psychologist were performed. RESULTS: In patients with PS-HypoPT, low Alb-Ca correlated with a worse performance on semantic memory abilities and executive function, as suggested by a significant inverse correlation between Alb-Ca and Trail Making Test A (TMT-A) scores (r = - 0.423; p = 0.014) and by a positive correlation with Semantic Fluency Test scores (SF)(r = 0.510; p = 0.002). PS-HypoPT patients with Alb-Ca ≤ 8.9 mg/dl had a significantly lower test performance compared with PS-HypoPT patients with Alb-Ca > 8.9 mg/dl, both at the TMT-A test (mean score: 34.53-18.55; p < 0.0001) and at SF test (mean score: 41.94-48.68; p = 0.01) and also a significantly lower test performance compared with control patients' group at TMT-A (mean score: 34.53-25.5; p = 0.0057). CONCLUSIONS: Patients with chronic PS-HypoPT in conventional therapy do not show a severe cognitive impairment; however, cognitive functions namely visuo-spatial attention, executive function and semantic memory appear to be modulated by Alb-Ca and impaired by its low levels.


Assuntos
Cálcio , Hipoparatireoidismo , Cognição , Estudos de Coortes , Humanos , Hipoparatireoidismo/etiologia , Complicações Pós-Operatórias/diagnóstico
6.
Osteoporos Int ; 33(5): 1155-1164, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35032187

RESUMO

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose Pós-Menopausa , Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Pós-Menopausa , Estudos Retrospectivos
7.
Front Public Health ; 10: 969288, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684879

RESUMO

Introduction: Asians and Pacific Islanders (APIs) who are experiencing homelessness are situated in a social intersection that has rendered them unrecognized and therefore vulnerable. There has been increasing attention to racial disparities in homelessness, but research into API homelessness is exceedingly rare, despite rapidly growing populations. The purpose of this study is to examine the causes of death among APIs who died while homeless in Santa Clara County (SCC) and compare these causes to other racial groups. Materials and methods: We report on data obtained from the SCC Medical Examiner-Coroner's Office on unhoused people's deaths that occurred between 2011 and 2021 (n = 1,394), including data on deaths of APIs experiencing homelessness (n = 87). Results: APIs comprised 6.2% of total deaths of unhoused people. APIs died less often of causes related to drug/alcohol use than all other racial groups (24.1, compared to 39.3%), and there was a trend toward more API deaths from injuries or illnesses. When APIs were disaggregated into sub-groups (East/Southeast Asian, South Asian, Pacific Islander), there were notable mortality differences in cause of death, age, and sex. Discussion: We argue that invisibility is a structural determinant of health that homeless APIs face. Though relatively small in numbers, APIs who are invisible may experience increased social isolation and, subsequently, specific increased mortality risks. To understand the health outcomes of unhoused APIs, it is essential that researchers and policymakers recognize API homelessness and gather and report disaggregated races and ethnicities.


Assuntos
Asiático , Pessoas Mal Alojadas , Humanos , População das Ilhas do Pacífico , Povo Asiático , Havaiano Nativo ou Outro Ilhéu do Pacífico
8.
ESMO Open ; 6(4): 100190, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144271

RESUMO

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia , Prognóstico , Quinolinas
9.
Exp Mech ; 61(1): 159-169, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33776070

RESUMO

BACKGROUND: In vivo characterization of mitral valve dynamics relies on image analysis algorithms that accurately reconstruct valve morphology and motion from clinical images. The goal of such algorithms is to provide patient-specific descriptions of both competent and regurgitant mitral valves, which can be used as input to biomechanical analyses and provide insights into the pathophysiology of diseases like ischemic mitral regurgitation (IMR). OBJECTIVE: The goal is to generate accurate image-based representations of valve dynamics that visually and quantitatively capture normal and pathological valve function. METHODS: We present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE), an imaging modality used for pre-operative surgical planning of mitral interventions. The framework integrates groupwise multi-atlas label fusion and template-based medial modeling with Kalman filtering to generate quantitatively descriptive and temporally consistent models of valve dynamics. RESULTS: The algorithm is evaluated on rt-3DE data series from 28 patients: 14 with normal mitral valve morphology and 14 with severe IMR. In these 28 data series that total 613 individual 3DE images, each 3D mitral valve segmentation is validated against manual tracing, and temporal consistency between segmentations is demonstrated. CONCLUSIONS: Automated 4D image analysis allows for reliable non-invasive modeling of the mitral valve over the cardiac cycle for comparison of annular and leaflet dynamics in pathological and normal mitral valves. Future studies can apply this algorithm to cardiovascular mechanics applications, including patient-specific strain estimation, fluid dynamics simulation, inverse finite element analysis, and risk stratification for surgical treatment.

11.
Am J Physiol Renal Physiol ; 320(2): F193-F202, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356952

RESUMO

Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1% oxygen) was achieved by using a hypoxia chamber. Phosphodiesterase 5 (PDE5) and sGC subunits were considerably expressed on the mRNA level in AA. PDE5 inhibition with sildenafil, which blocks cGMP degradation, diminished the responses to ANG II bolus application in AA, but not significantly in EA. Vasodilation induced by sildenafil in ANG II-preconstricted vessels was stronger in EA than AA. Cinaciguat, an NO- and heme-independent sGC activator, dilated EA more strongly than AA after NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) treatment and preconstriction with ANG II. Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.


Assuntos
Angiotensina II/farmacologia , Arteríolas/enzimologia , Rim/irrigação sanguínea , Guanilil Ciclase Solúvel/metabolismo , Animais , Arteríolas/fisiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico , Inibidores da Fosfodiesterase 5/farmacologia , Guanilil Ciclase Solúvel/genética
12.
J Nutr Health Aging ; 24(10): 1111-1115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244569

RESUMO

OBJECTIVES: We examined the relationship between absolute income, adequacy of disposable income, and self-rated health among participants aged 60 years and over. DESIGN: Cross sectional study. SETTING: Community living older people in Hong Kong. PARTICIPANTS: Older people aged 60 years and over in five districts in Hong Kong. MEASUREMENTS: Data from a cross sectional survey of age friendly characteristics across five districts of Hong Kong carried out using stratified random sampling across a broad range of socioeconomic attributes. RESULTS: Self-rated health showed a gradient for both absolute and adequacy of disposable income. The OR for the association between having just enough, or insufficient disposable income and poor health was higher: 2.0 and 3.6 respectively, and higher than that for absolute income (OR 1.8), and remained significant after adjustment for absolute income. No association between absolute income and self-rated health was observed among women. These findings suggest that adequacy of disposable income provide a stronger association with self-rated health compared with absolute income among older people aged 60 years and over, particularly for women. The absolute income corresponding to what is considered adequate disposable income lies between HK$4000-10000. CONCLUSION: Adequacy of disposable income may be a better indicator than absolute income for older people in examining the relationship with health outcomes, particularly for older women.


Assuntos
Nível de Saúde , Pobreza/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Renin Angiotensin Aldosterone Syst ; 21(4): 1470320320966177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33094663

RESUMO

HYPOTHESIS: A lack of contraction of cerebral microarterioles to Ang II ("resilience") depends on cyclooxygenase (COX) and lipocalin type prostaglandin D sythase L-PGDS producing PGD2 that activates prostaglandin D type 1 receptors (DP1Rs) and nitric oxide synthase (NOS). MATERIALS & METHODS: Contractions were assessed in isolated, perfused vessels and NO by fluorescence microscopy. RESULTS: The mRNAs of penetrating intraparenchymal cerebral microarterioles versus renal afferent arterioles were >3000-fold greater for L-PGDS and DP1R and 5-fold for NOS III and COX 2. Larger cerebral arteries contracted with Ang II. However, cerebral microarterioles were entirely unresponsive but contracted with endothelin 1 and perfusion pressure. Ang II contractions were evoked in cerebral microarterioles from COX1 -/- mice or after blockade of COX2, L-PGDS or NOS and in deendothelialized vessels but effects of deendothelialization were lost during COX blockade. NO generation with Ang II depended on COX and also was increased by DP1R activation. CONCLUSION: The resilience of cerebral arterioles to Ang II contractions is specific for intraparenchymal microarterioles and depends on endothelial COX1 and two products that are metabolized by L-PGDS to generate PGD2 that signals via DP1Rs and NO.


Assuntos
Arteríolas/fisiologia , Células Endoteliais/metabolismo , Perfusão , Prostaglandina D2/metabolismo , Vasoconstrição , Angiotensina II , Animais , Células Cultivadas , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Angiotensina/metabolismo , Receptores de Prostaglandina/metabolismo , Vasoconstrição/efeitos dos fármacos
14.
J Urol ; 202(6): 1273, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31389762
15.
Lupus ; 28(8): 945-953, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177913

RESUMO

The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.


Assuntos
Artrite Reumatoide/complicações , Indicadores Básicos de Saúde , Lúpus Eritematoso Sistêmico/complicações , Fraturas por Osteoporose/epidemiologia , Síndrome de Sjogren/complicações , Absorciometria de Fóton , Adulto , Idoso , Algoritmos , Densidade Óssea , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Taiwan/epidemiologia
16.
BMC Pediatr ; 19(1): 150, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31088415

RESUMO

BACKGROUND: Childhood unintentional injuries (UI) are common but continue to happen more often to children living in less advantaged socioeconomic circumstances (SEC). Our aim was to explore how early life factors mediate the association between SEC and UIs, using the UK Millennium Cohort Study. METHODS: We calculated risk ratios (RR) and 95% confidence intervals (95%CI) for parental report of UI occurring between age 3 and 5 years, using Poisson regression according to family income as a measure of SEC. We explored potentially mediating pathways by controlling associations between SEC and UI for groups of early life risks in three domains: factors that may influence environmental safety, supervision and the MCS child's abilities and behaviours. RESULTS: Twenty eight percent of children had a UI from 3 to 5 years old. Children from the lowest income quintile were more likely to be injured compared to those from the highest (RR 1.20 95%CI 1.05, 1.37). Sequentially controlling for early life factors that may influence environmental safety (RR 1.19 95%CI 1.02, 1.38), then supervision (RR 1.18, 95%CI 1.02, 1.36), and finally adding child's behaviour and abilities (RR 1.15, 95%CI 1.00, 1.34) into the model reduced the RR by 5, 10 and 25% respectively. CONCLUSIONS: Addressing factors that may influence environmental safety and supervision, and the child's abilities and behaviours only partly explains the increased UI risk between the highest and lowest income quintiles. Further research is required to explore factors mediating associations between SEC and specific mechanisms and types of injuries.


Assuntos
Lesões Acidentais/diagnóstico , Lesões Acidentais/epidemiologia , Proteção da Criança , Renda , Fatores Etários , Distribuição de Qui-Quadrado , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Escala de Gravidade do Ferimento , Estudos Longitudinais , Masculino , Razão de Chances , Prevalência , Medição de Risco , Fatores Socioeconômicos , Reino Unido/epidemiologia
18.
Int Endod J ; 52(5): 676-688, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30537112

RESUMO

AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.


Assuntos
Reabsorção Óssea , Periodontite Periapical , Animais , Apoptose , Humanos , Mitofagia , Osteoblastos , Ratos , Sinvastatina
19.
Hong Kong Med J ; 24(5): 527-531, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30318478

RESUMO

Vaccination of egg-allergic individuals has been a historical concern, particularly for influenza and measles-mumps-rubella-varicella vaccines that are developed in chicken egg embryos or chicken cell fibroblasts. The egg proteins in these vaccines were believed to trigger an immediate allergic reaction in egg-allergic individuals. However, recently published international guidelines have updated their recommendations and now state that these vaccines can be safely administered to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases summarises the updates and provides recommendations for local general practitioners and paediatricians. Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients Background.


Assuntos
Controle de Doenças Transmissíveis , Hipersensibilidade a Ovo , Hipersensibilidade/prevenção & controle , Vacinação/normas , Criança , Serviços de Saúde da Criança , Consenso , Feminino , Hong Kong , Humanos , Masculino , Sociedades Médicas
20.
Bone Joint J ; 100-B(6): 780-786, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29855232

RESUMO

Aims: A high rate of suicide has been reported in patients who sustain fractures, but the association remains uncertain in the context of other factors. The aim of this study was to examine the association between fractures and the risk of suicide in this contextual setting. Patients and Methods: We performed a case-control study of patients aged 40 years or older who died by suicide between 2000 and 2011. We included patients' demographics, physical and mental health problems, and socioeconomic factors. We performed conditional logistic regression to evaluate the associations between fractures and the risk of suicide. Results: We included a total of 34 794 patients who died by suicide and 139 176 control patients. We found that fractures as a homogenous group (adjusted odds ratios (aOR), 1.48; 95% confidence interval (CI) 1.43 to 1.53), and specifically pelvic (aOR 2.04; 95% CI 1.68 to 2.47) and spinal fractures (aOR 1.53; 95% CI 1.43 to 1.64), were associated with a higher risk of suicide. In addition, we found that patients who had a lower income, had never married, had lower levels of educational attainment, or had coexistent physical and mental conditions such as anxiety, mood disorders, and psychosis-related disorders had a higher risk of suicide. Conclusion: Fractures, specifically those of the hip and spine, were associated with an increased risk of suicide. The findings suggest that greater clinical attention should be given to this risk in patients with fractures, especially for those with additional risk factors. Cite this article: Bone Joint J 2018;100-B:780-6.


Assuntos
Fraturas Ósseas/complicações , Suicídio/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Bases de Dados Factuais , Feminino , Fraturas Ósseas/psicologia , Humanos , Modelos Logísticos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Suicídio/psicologia , Taiwan
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