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1.
J Diabetes ; 13(1): 89-93, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33040469

RESUMO

Highlights Fasting blood glucose < 10 mmol/L was proposed as a target of glycemic control during the first week of hospitalization in patients with preexisting diabetes. Poor HbA1c levels prior to coronavirus disease 2019 (COVID-19) might not be associated with severity among patients with preexisting diabetes. Mean blood glucose seemed not to be associated with poor prognosis of COVID-19.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/sangue , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Hypertens Res ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33162551

RESUMO

Reservoir pressure parameters (i.e., reservoir pressure [RP] and excess pressure [XSP]) independently predict cardiovascular events in adults, but this has not been investigated in children. This study aimed to determine (1) the association of reservoir pressure parameters with carotid intima-media thickness (carotid IMT), a preclinical vascular phenotype, and (2) whether a multivariable regression model with or without reservoir pressure parameters fits better for estimating carotid IMT in children. Study participants were 11-12-year-old children (n = 1231, 50% male) from the Child Health CheckPoint study, a cross-sectional substudy of the population-based Longitudinal Study of Australian Children. RP and XSP were obtained using brachial-cuff oscillometry (SphygmoCor XCEL, AtCor, Sydney). Carotid IMT was quantified by vascular ultrasonography. XSP was associated with carotid IMT after adjusting for confounders including age, sex, BMI z-score, heart rate, pubertal stage, moderate-to-vigorous physical activity, and mean arterial pressure (ß = 0.93 µm, 95% CI 0.30-1.56 for XSP peak and ß = 0.04 µm, 95% CI 0.01-0.08 for XSP integral). The results of the likelihood ratio test indicated a trend that the model with XSP and the above confounders fit better than a similar model without XSP for estimating carotid IMT. Our findings indicate that brachial-cuff device-measured XSP is associated with carotid IMT independent of conventional cardiovascular risk factors, including standard BP. This implies that a clinically convenient cuff approach could provide meaningful information for the early assessment of cardiovascular risk among children.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33253381

RESUMO

OBJECTIVE: To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. METHODS: In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. RESULTS: Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. CONCLUSIONS: In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.

4.
Intern Med J ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975868

RESUMO

BACKGROUND: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. AIM: To describe the association between SES and time to THR and TKR. METHODS: 1072 older-adults residing in Tasmania, Australia were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined by the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD), from the Australian Bureau of Statistics' 2001 census data. IRSAD was analysed in two ways; 1) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group, 2) the cohort dichotomised at the quartile 1 cut-point. RESULTS: The mean age was 63.0 (±7.5) years, and 51% were women. Over the median follow-up of 12.9 (Interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR, and 79 (7%) had a TKR. Compared to the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR) (HR: 0.56, 95% CI 0.32, 1.00) but not TKR (HR: 0.90, 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. CONCLUSIONS: This study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. This article is protected by copyright. All rights reserved.

5.
Ann Intern Med ; 173(11): 861-869, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926799

RESUMO

BACKGROUND: Current pharmacologic therapies for patients with osteoarthritis are suboptimal. OBJECTIVE: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. DESIGN: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). SETTING: Single-center study with patients from southern Tasmania, Australia. PARTICIPANTS: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. INTERVENTION: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. MEASUREMENTS: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. RESULTS: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. LIMITATION: Modest sample size and short duration. CONCLUSION: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. PRIMARY FUNDING SOURCE: University of Tasmania and Natural Remedies Private Limited.

6.
Am J Clin Nutr ; 112(1): 48-56, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401318

RESUMO

BACKGROUND: Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. OBJECTIVES: We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. METHODS: An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. CONCLUSIONS: Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.


Assuntos
Densidade Óssea/efeitos dos fármacos , Cálcio na Dieta/administração & dosagem , Cálcio/administração & dosagem , Adulto , Suplementos Nutricionais/análise , Feminino , Humanos , Lactação/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
7.
JAMA ; 323(15): 1456-1466, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315057

RESUMO

Importance: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. Objective: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. Design, Setting, and Participants: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Interventions: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. Main Outcomes and Measures: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Results: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. Trial Registration: anzctr.org.au Identifier: ACTRN12613000039785.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças da Medula Óssea/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Medula Óssea/patologia , Doenças da Medula Óssea/complicações , Doenças da Medula Óssea/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Falha de Tratamento , Ácido Zoledrônico/administração & dosagem
8.
Mol Ther Nucleic Acids ; 19: 393-404, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31887550

RESUMO

Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot, and dual-luciferase reporter assay. H19 small interfering RNA (siRNA) (Si-H19) and adenovirus (AD-H19) were used to decrease and increase H19 expression, respectively. 42 annotated lncRNAs were identified, and H19 was overexpressed. H19, vitamin D receptor (VDR), and transforming growth factor ß (TGF-ß) can bind to microRNA22-5p (miR22-5p) and miR675-5p. Si-H19 significantly downregulated miR22-5p and upregulated miR675-5p expression; Si-H19 decreased the protein and mRNA expression of VDR and decreased the cytokine and mRNA levels of interleukin-17A (IL-17A) and IL-23. These results were verified by AD-H19. In addition, miR22-5p and miR675-5p inhibitors increased the protein and mRNA expression of VDR and increased the cytokine and mRNA levels of IL-17A and IL-23. These results were also confirmed by miRNA mimics. Furthermore, H19 directly interfered with miR22-5p and miR675-5p expression, whereas the two miRNAs directly inhibited VDR expression. Overall, the H19-miR22-5p/miR675-5p-VDR-IL-17A/IL-23 signaling pathways have important roles in the pathogenesis of AS.

9.
Arthritis Res Ther ; 21(1): 273, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818318

RESUMO

BACKGROUND: To describe the association of age, sex and body mass index with the rate of change of tibial knee cartilage volume over 10.7 years in a community-based sample of older adults. METHODS: Four hundred and eighty-one participants (49% female, mean age 60.8 years [range 51.1-79.7], 49% had knee pain and 58% radiographic osteoarthritis) were included. Tibial cartilage volume of the right knee was assessed on T1-weighted fat-suppressed 1.5 T MRI at baseline and 10.7 years. Data analyses were performed using linear regression models. RESULTS: The average rate of loss of cartilage volume was 1.2%/year (range 0.2-3.9%) with all participants losing cartilage volume over the study period. There was a significant association between age and loss of tibial cartilage volume in the medial (0.023%/year, 95% confidence interval [CI] 0.010 to 0.036%, p < 0.001), lateral (0.013%/year, 95% CI 0.003 to 0.023%, p = 0.012) and total tibia (0.018%/year, 95% CI 0.009 to 0.026%, p < 0.001). Higher body mass index at baseline and increases in body mass index over time were associated with a greater tibial cartilage loss at the medial (body mass index at baseline 0.040%/year, 95% CI 0.022 to 0.058%, p < 0.001; increases in body mass index 0.055%/year, 95% CI 0.018 to 0.093%, p = 0.004) but not lateral compartment. No evidence of non-linear relationships was observed. Compared to males, females lost more lateral tibial cartilage with increasing age (0.023%/year, 95% CI 0.003 to 0.043%, p = 0.024 for interaction). CONCLUSIONS: Tibial cartilage volume declines at a faster rate with increasing age and body mass index in both males and females, particularly in the medial compartment. In contrast to the low rate of change in radiographs, our findings suggest that cartilage loss at the tibia is universal in this age group.


Assuntos
Cartilagem Articular/patologia , Articulação do Joelho/patologia , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Fatores Sexuais , Tíbia
10.
Ther Adv Musculoskelet Dis ; 11: 1759720X19880054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692649

RESUMO

Background: The aim of this study was to compare the efficacy and safety of zoledronic acid (ZA) plus intravenous methylprednisolone (VOLT01) to ZA, and placebo for knee osteoarthritis. Methods: A single-center, double-blind, randomized controlled trial (RCT) was carried out. Adults (aged ⩾50 years) with knee osteoarthritis, significant knee pain [⩾40 mm on a 100 mm visual analog scale (VAS)], and magnetic resonance imaging-detected bone marrow lesion (BML) were randomized to receive a one-off administration of VOLT01, ZA, or placebo. The primary hypothesis was that VOLT01 was superior to ZA in having a lower incidence of acute phase responses (APRs) over 3 days. Secondary hypotheses were that VOLT01 was noninferior to ZA, and both treatments were superior to placebo in decreasing BML size over 6 months and in improving knee pain [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and VAS] and function (WOMAC) over 3 and 6 months. Results: A total of 117 patients (62.2 ± 8.1 years, 63 women) were enrolled. The incidence of APRs was similar in the VOLT01 (90%) and ZA (87%) groups (p = 0.74). VOLT01 was superior to ZA in improving knee pain and function after 6 months and noninferior to ZA in reducing BML size. However, BML size change was small in all groups and there were no between-group differences. Compared with placebo, VOLT01 but not ZA improved knee function and showed a trend toward improving knee pain after 6 months. Conclusions: Administering intravenous methylprednisolone with ZA did not reduce APRs or change knee BML size over 6 months, but in contrast to ZA or placebo, it may have a beneficial effect on symptoms in knee osteoarthritis. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785.

11.
BMC Musculoskelet Disord ; 19(1): 217, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021646

RESUMO

BACKGROUND: Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients. METHODS: Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785 , registered on 14 January 2013.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/tratamento farmacológico , Dor/diagnóstico por imagem , Dor/tratamento farmacológico , Ácido Zoledrônico/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Articulação do Joelho/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
12.
J Bone Miner Res ; 33(5): 773-782, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29297602

RESUMO

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T12 -S1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research.


Assuntos
Denosumab/administração & dosagem , Dor Lombar/tratamento farmacológico , Ácido Zoledrônico/administração & dosagem , Adulto , Idoso , Denosumab/efeitos adversos , Feminino , Humanos , Dor Lombar/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Fatores de Tempo , Ácido Zoledrônico/efeitos adversos
13.
PLoS One ; 12(5): e0177080, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28493913

RESUMO

OBJECTIVES: Previous studies have found the association between rs10865331 in 2p15 area and ankylosing spondylitis (AS). This study aimed to identify additional functional genetic variants in 2p15 region associated with AS susceptibility. METHODS: We used next generation sequencing (NGS) in 100 AS cases and 100 healthy controls to screen AS susceptible genetic variants, and validated these variants in 620 cases and 620 controls by using imLDRTM technique for single nucleotide polymorphism (SNP) genotyping. RESULTS: Totally, we identified 12 SNPs that might confer susceptibility to AS. Of those SNPs, three (rs14170, rs2123111 and rs1729674) were nominally associated (P<0.05) with AS, but were no longer statistically significant after Bonferroni correction. After stratified by gender, another two SNPs (rs11428092 and rs10208769 in USP34) were associated with AS in males but not females, though this was not statistically significant after Bonferroni correction. In addition, rs1729674, rs14170, rs2123111 and rs10208769 were in strong linkage disequilibrium (LD) and were further enrolled in haplotype analysis. A novel haplotype TAGA was found to be associated with a decreased risk of AS (odds ratio (OR) (95% confidence interval (CI)) = 0.832 (0.705-0.982)). Beyond that, we also demonstrated a strong relationship between rs10865331 and AS susceptibility (OR (95% CI) = 1.303(1.111-1.526)). CONCLUSIONS: rs14170 and rs2123111 inUSP34 and rs1729674 in C2orf74 may be associated with AS susceptibility in Han Chinese population. USP34 and C2orf74 in 2p15 region may be AS novel susceptibility genes.


Assuntos
Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/genética , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Desequilíbrio de Ligação , Masculino , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Espondilite Anquilosante/epidemiologia , Proteases Específicas de Ubiquitina/genética
14.
Health Qual Life Outcomes ; 14(1): 118, 2016 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-27549129

RESUMO

BACKGROUND: To examine the subjective well-being (SWB) in patients with ankylosing spondylitis (AS) compared with the healthy controls, and to explore the associations between SWB and demographic characteristics, disease-specific variables in AS patients. METHODS: SWB was assessed with General Well-Being Schedule (GWBS) in 200 AS patients and 210 healthy controls. Comparisons among subgroups were performed to investigate how certain aspects operate as favorable or adverse factors in influencing SWB in the patients with AS. RESULTS: Both men and women with AS reported significantly impaired SWB on all scales of the GWBS except for the Control (O) scale. The results revealed that better sleep, lower disease activity and more family care predicted higher SWB. In AS patients, positive attitude towards therapy prospect was significantly associated with higher SWB. Therapy prospect refers to the hope of patients about the disease treatment. CONCLUSIONS: Compared with general population, SWB might be affected by the onset of AS. There are significant associations between SWB and sleep quality, BASDAI, APGAR, therapy prospect.


Assuntos
Ajustamento Emocional , Qualidade de Vida/psicologia , Autoeficácia , Espondilite Anquilosante/psicologia , Adaptação Psicológica , Adulto , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Estresse Psicológico/etiologia
15.
Rheumatol Int ; 36(8): 1157-65, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27255295

RESUMO

The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg's funnel plot and Egger's tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213-1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365-1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians.


Assuntos
Predisposição Genética para Doença , Proteínas Facilitadoras de Transporte de Glucose/genética , Gota/genética , Polimorfismo de Nucleotídeo Único , Alelos , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos
16.
J Clin Neurosci ; 30: 1-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27283386

RESUMO

It has been reported that two single nucleotide polymorphisms (SNP) Taq1A and -141C Ins/Del in the DRD2 gene may be associated with susceptibility to schizophrenia. Due to inconclusive and mixed results, a meta-analysis was conducted to further clarify the relationship between the two SNP and schizophrenia susceptibility. A systematic literature search for the association of these two SNP with schizophrenia susceptibility was conducted using PubMed, ScienceDirect, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the associations reported. A total of 5558 schizophrenic patients and 6792 healthy controls from 31 articles were included in this study. Evidence regarding the association between -141C Ins/Del polymorphism and schizophrenia was found in the allele frequency comparison (Ins versus Del: OR 1.29, 95% CI 1.06-1.57; p=0.01, Praw=0.1, PFalse Discovery Rate=0.023). In ethnic subgroup analysis, the result revealed that the 141C Ins/Del polymorphism was associated with schizophrenia in all genetic models in Asians, but not in Caucasians. For Taq1A polymorphism, a significant association was found in the allele frequency (A1 versus A2: OR 0.71, 95% CI 0.52-0.98, p=0.03). Stratification by ethnicity indicated an association between the Taq1A polymorphism and schizophrenia in Asians, but not Caucasians. The present study suggests that the -141C Ins/Del polymorphism carries a significantly increased risk of schizophrenia, while the Taq1A polymorphism carries a significantly decreased risk of schizophrenia susceptibility in Asians.


Assuntos
Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino
17.
Qual Life Res ; 25(11): 2711-2723, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27324038

RESUMO

PURPOSE: The main purpose of this meta-analysis was to evaluate the impact of ankylosing spondylitis on the health-related quality of life assessed by the Medical Outcomes Short-Form-36 questionnaire (SF-36). METHODS: A systematic literature search was performed on PubMed and Web of Science until January 22, 2016 to obtain eligible studies. Random effect model was performed to summarize the scores of each domain. The radar chart was used to compare the scores of AS patients with other health conditions. Spearman's correlation analysis and meta-regression were used to explore the related factors. STATA (version 11.0) and SPSS (version 13.0) were adopted in this meta-analysis. RESULTS: Thirty-eight studies were included in this study, which were all reliable to summarize the scores of the SF-36. Pooled mean scores of the physical health domains ranged from 45.93 to 58.17, with the RP and PF domains being the lowest and the highest, respectively. Pooled mean scores of the mental health domains ranged from 47.49 to 62.52, with the VT and SF domains being the lowest and the highest, respectively. Besides, the physical component summary was lower than the mental component summary. BASDAI and BASFI were negatively associated with some domains of the SF-36 significantly. Patients with AS had a substantial impaired HRQoL in comparison with the general population. CONCLUSIONS: AS could adversely affect the HRQoL of patients. Measuring HRQoL should be considered as an essential part of the overall assessment of health status of AS patients, which would provide valuable clues for improving the management of disease and making decisions regarding treatment.


Assuntos
Qualidade de Vida/psicologia , Espondilite Anquilosante/psicologia , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários
18.
Clin Exp Rheumatol ; 34(3): 539-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27050563

RESUMO

OBJECTIVES: The main purpose of this meta-analysis is to evaluate the diagnostic value of anti-RA33 antibody for rheumatoid arthritis. METHODS: In order to obtain eligible studies, a systematic literature search was performed on PubMed, Web of science, EBSCO, CNKI and CBM from January 2000 to September 2015. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the quality of the relevant studies. Meta-disc 1.4 and Stata 11.0 were adopted in this meta-analysis. RESULTS: After rigorous review, fifty studies were included in this study, which are all reliable to summarise the diagnostic value in this meta-analysis. The result of the analysis shows the pooled sensitivity is 0.33 (95% confidence interval (CI): 0.31-0.34) and the specificity is 0.90 (95% CI: 0.89-0.90), for the diagnosis of rheumatoid arthritis. Besides, the area under the summary ROC curve (AUC) is 0.6863. CONCLUSIONS: The current evidence suggests that anti-RA33 antibody has high diagnostic specificity value for rheumatoid arthritis, which may be useful for the disease diagnostic application. To verify this conclusion, more prospective research on the diagnostic value of anti-RA33 antibody for rheumatoid arthritis are needed in the future.


Assuntos
Anticorpos Antinucleares , Artrite Reumatoide , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/imunologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
19.
Mod Rheumatol ; 26(1): 146-50, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26025437

RESUMO

OBJECTIVES: To explore the association of ß-defensin gene copy number variations (CNVs) with ankylosing spondylitis (AS). METHODS: In this study, 405 unrelated Chinese Han patients with AS and 401 unrelated healthy controls were enrolled. The copy numbers of DEFB4 gene (2 fragments) were measured by AccuCopy™ methods. The association of DEFB4 gene CNVs with AS susceptibility was analyzed by chi-square and logistic regression models. Besides, P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. RESULTS: The range of DEFB4_1 CN was 0-7 and the range of DEFB4_2 CN was 1-8 both in patients and controls. P values of χ(2) trend test for the association of DEFB4_1 and DEFB4_2 with AS were 0.607 and 0.005, respectively. The results of DEFB4_2, compared with the individual having median 3 copies, those carrying ≤ 2-copies [OR = 0.68, 95%CI: (0.46, 0.99), P = 0.049; adjusted OR = 0.69, 95%CI(0.47, 1.03), P = 0.067.]; and those carrying ≥ 4-copies [OR = 0.62, 95%CI: (0.45, 0.86), P = 0.004; adjusted OR = 0.64, 95%CI: (0.46, 0.88), P = 0.006], were significantly associated with decreasing risk of AS. Univariate analysis showed that both DEFB4_1 and DEFB4_2 were associated with Bath AS Disease Activity Index or BASDAI. After adjusted by age, sex, and disease duration, the results changed little, which demonstrated that high copies may be linked with decrease in the risk of disease severity [OR = 0.71, 95%CI: (0.56, 0.90), P = 0.005; OR = 0.75, 95%CI: (0.60, 0.94), P = 0.013, respectively]. CONCLUSIONS: The CNs of DEFB4 gene may be associated with AS and involved in disease progression.


Assuntos
Variações do Número de Cópias de DNA , Dosagem de Genes , Espondilite Anquilosante/genética , beta-Defensinas/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Adulto Jovem
20.
Rheumatol Int ; 36(3): 437-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26494566

RESUMO

Ankylosing spondylitis (AS) is a common inherited autoimmune disease. Copy number variation (CNV) of DNA segments has been found to be an important part of genetic variation, and the FCGR3A and FCGR3B gene CNVs have been associated with various autoimmune disorders. The aim of the study was to determine whether CNVs of FCGR3A and FCGR3B were also associated with the susceptibility of AS. A total of 801 individuals including 402 AS patients and 399 healthy controls were enrolled in this study. The copy numbers of FCGR3 gene (two fragments, included FCGR3A and FCGR3B) were measured by AccuCopy™ methods. Chi-square test and logistic regression model were used to evaluate association between FCGR3 gene CNVs and AS susceptibility. P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Significantly, difference in the frequencies of FCGR3A and FCGR3B gene CNVs was founded between the patients with AS and controls. For the FCGR3A gene, a low (≤3) copy number was significantly associated with AS [for ≤3 copies versus 4 copies, (OR 2.17, 95% CI (1.41, 3.34), P < 0.001, adjusted OR 2.22, 95% CI (1.44, 3.43), P < 0.001)]. A low FCGR3B copy number was also significantly associated with increasing risk of AS [for ≤3 copies versus 4 copies, (OR 1.87, 95% CI (1.25, 2.79), P = 0.002, adjusted OR 1.94, 95% CI (1.29, 2.91), P = 0.001)]; however, both the high FCGR3A and FCGR3B copy numbers (≥5) were not significantly associated with the risk of AS (≥5 copies versus 4 copies). The lower copy numbers (≤3) of FCGR3A and FCGR3B genes confer a risk factor for AS susceptibility.


Assuntos
Variações do Número de Cópias de DNA , Dosagem de Genes , Receptores de IgG/genética , Espondilite Anquilosante/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Proteínas Ligadas por GPI/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Fenótipo , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/etnologia , Adulto Jovem
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