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1.
Biomarkers ; : 1-7, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31920111

RESUMO

Background: The purpose of this meta-analysis was to evaluate the relationship between elevated cardiac troponin pre-transcatheter aortic valve replacement (TAVR) and long-term all-cause mortality.Methods: Prospective studies with the endpoint of all-cause mortality were included. We primarily used the fixed-effect model weighted by inverse variance. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics.Results: Seven prospective studies comprising of 3049 subjects were included in our meta-analysis. Pre-procedural elevated cardiac troponin was associated with increased risk of long-term mortality post TAVR [hazard ratio (HR) 2.25, 95% CI 1.83-2.78, p = 0.000, I2 = 30.3%, p for heterogeneity 0.197]. In addition, subgroup analyses have shown that the group with an younger age (<82 y) seemed to have a higher risk of all-cause mortality than the group with older age (≥82 y) [HR 4.08 (2.41 to 6.89) VS 2.01 (1.60 to 2.53), p = 0.016 for subgroup difference].Conclusions: Pre-procedural elevated cardiac troponin was associated with increased long-term all-cause mortality in patients undergoing TAVR.

2.
Gene ; 734: 144395, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31987907

RESUMO

Studies imply the FOXP3 gene polymorphisms are engaged in the occurrence of some cancers, but the relationship between FOXP3 rs2280883 polymorphism and the hazard of colorectal cancer (CRC) is unclear. For this reason, a case-control investigation involving 365 CRC patients and 411 healthy individuals (matched by both age and gender) was taken to illustrate the underlying association. FOXP3 rs2280883 polymorphism genotyped via PCR-RELP. Data revealed this polymorphism was significantly linked to increased risk for CRC (CC versus TT, OR, 1.75; 95%CI, 1.06-2.88; P = 0.030). Subgroup analyses uncovered FOXP3 rs2280883 polymorphism intensified the risk of CRC among smokers. As for the connection between rs2280883 and clinical data of CRC, this polymorphism corelated to lymph node metastasis (CC versus TT: OR, 2.75; 95%CI, 1.35-5.62; P = 0.004) and the TNM stage. In conclusion, FOXP3 rs2280883 polymorphism is related to higher risk of CRC in a Chinese individuals. Larger-sized studies involving other races are needed.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31815008

RESUMO

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via ß-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.

6.
Cell Regen (Lond) ; 8(2): 31-32, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31534714
7.
Am J Hypertens ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549136

RESUMO

BACKGROUND: Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the current study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS: Peripheral blood samples were collected from all subjects for DNA extraction. Next generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS: Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Co-segregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with nine different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS: Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long term follow-up to prevent stroke and adverse cardiovascular events.

8.
J Hum Hypertens ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488861

RESUMO

Primary aldosteronism (PA) is mainly treated by mineralocorticoid receptor antagonists or laparoscopic adrenalectomy (LA), but the effectiveness of surgical versus medical treatment in patients with adrenal venous sampling (AVS)-proven unilateral PA is unclear. Fifty-one consecutive patients with AVS-proven PA were enrolled. We compared the therapeutic effects between the surgery group (n = 21) and medication group (n = 30) by evaluating the complete control rate (CCR) of hypertension, blood pressure (BP), and number of antihypertensive drugs after a long-term follow-up (>12 months). The CCR of hypertension was assessed using a multivariate adjusted Cox proportional hazards regression model. After a mean follow-up of 21.18 ± 5.35 months, the CCR was significantly higher in the surgery than medication group (85.7% vs. 13.3%, respectively; p < 0.001). Before adjustment for covariates, the CCR of hypertension in patients who underwent LA was 7.75 times higher than that in patients who underwent medical treatment (95% CI, 2.33-25.78; p = 0.001); significant results were also shown in the adjusted models. Systolic and diastolic BP were also lower in the surgery than medication group (120.3 ± 12.99 vs. 133.54 ± 16.60 and 79.00 ± 7.62 vs. 87.35 ± 12.36 mmHg, respectively; p = 0.01 for both), as was the number of antihypertensive drugs (0.19 ± 0.51 vs. 2.33 ± 0.78, respectively; p < 0.001). The rate of hypokalemia was not significantly different between the two groups (0.0% vs. 13.3%, respectively; p = 0.13). In conclusion, AVS plays an essential role in the subtype diagnosis of PA, and surgical candidates with AVS-proven unilateral PA should be highly suggested to undergo LA.

9.
Am J Hypertens ; 32(10): 1021-1029, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31278892

RESUMO

BACKGROUND: To investigate the clinical features, management, and outcomes of childhood Takayasu arteritis (c-TA) initially presenting with hypertension. METHODS: This study retrospectively reviewed medical charts of 96 inpatient c-TA cases from January 2002 to December 2016, with 5 additional patients being prospectively recruited from January 2017 to December 2017. Data were compared between c-TA groups initially presenting with and without hypertension. Blood pressure (BP) control, event-free survival, and associated risk factors were assessed by logistic regression, Kaplan-Meier survival curve, and COX regression models. RESULTS: The hypertensive cohort (N = 71, 28.2% males) as compared with non-hypertensive cohort had significantly fewer active diseases; fewer episodes of claudication, syncope, blurred vision, and myocardial ischemia; and fewer systemic symptoms (P < 0.05). The hypertensive group presented with more localized abdominal lesions (OR = 14.4, P = 0.001) and limited supradiaphragmatic arterial involvement. Renovascular disease (P = 0.001) and revascularization (P = 0.006) were associated with hypertension. At the median 3-year follow-up, 53% of hypertensive patients achieved BP control and 39% experienced events including vascular complications, flares, or death. The 1-, 3-, 5-, and 10-year event-free survival were 78.7% (95% CI: 65.7%-87.2%), 63.0% (95% CI: 48.1%-74.7%), 48.9% (95% CI: 32.0%-63.8%), and 31.6% (95% CI: 13.8%-51.2%), higher than in non-hypertensive group (P = 0.014). Heart failure, stroke, and body mass index <18.5 kg/m2 were prognostic factors for events. Intervention and baseline systolic BP were independent factors for BP control (P < 0.05). CONCLUSIONS: Majority of c-TA has hypertension, presenting with a more quiescent disease without typical systemic and/or ischemia symptoms, more localized abdominal lesions, higher proportion of revascularizations and better event-free survival. Three-year BP control is more than 50%. Intervention particularly on renal artery is beneficial for BP control and decreased events. CLINICAL TRIAL REGISTRATION: Trial Number: NCT03199183.

10.
Huan Jing Ke Xue ; 40(3): 1270-1279, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087974

RESUMO

The index of biotic integrity (IBI) has been widely used in river ecosystem health assessment. However, few studies have reported the application of microbial communities in ecosystem health assessment so far, especially for urban rivers. In this study, the Illumina high-throughput sequencing technique was applied to analyze the microbial community diversity and composition of five urban rivers selected in Zhejiang Province. Canonical correlation analyses (CCA) and Spearman correlation analysis were used to evaluate the relationship between each taxonomic group and the water quality properties to select the most sensitive taxonomic groups as candidate indexes. The functional metrics, including the relative abundance of pathogenic bacteria, pollutant-degrading bacteria, and nutrient cycling bacteria were also selected as candidate indexes. Based on the distribution range, discriminatory power, and Pearson's correlation analysis for candidate indexes, five metrics, including the Shannon-index, the number of microbial phyla, the relative abundance of Verrucomicrobia, Chlorobi, and Mycobacterium were selected to establish a biotic integrity index of microbes (M-IBI) evaluation system. A ratio score system was used to get metrics into a uniform score for all sampling points, and the results showed that among the urban river samples studied, most of them (40.9%) were at "Great" level, 45.5% were at "Good" level, 9.1% were at "Moderate" level, and 4.5% were at "Bad" level. The index of M-IBI effectively discriminated the least, medium, and highly impaired sampling points and provided a good match with the water quality (R=0.753, P<0.01), indicating that the M-IBI has potential as an index to evaluate the health of urban river ecosystems.


Assuntos
Ecossistema , Monitoramento Ambiental , Microbiota , Rios/microbiologia , Qualidade da Água , Bactérias/classificação , China
11.
Am J Hypertens ; 32(8): 752-758, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30977777

RESUMO

BACKGROUND: Liddle syndrome (LS) is an autosomal dominant disorder caused by single-gene mutations of the epithelial sodium channel (ENaC). It is characterized by early-onset hypertension, spontaneous hypokalemia and low plasma renin and aldosterone concentrations. In this study, we reported an LS pedigree with normokalemia resulting from a novel SCNN1G frameshift mutation. METHODS: Peripheral blood samples were collected from the proband and eight family members for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the SCNN1G mutation. Clinical examinations were used to comprehensively evaluate the phenotypes of two patients. RESULTS: Genetic analysis identified a novel SCNN1G frameshift mutation, p.Arg586Valfs*598, in the proband with LS. This heterozygous frameshift mutation generated a premature stop codon and deleted the vital PY motif of ENaC. The same mutation was present in his elder brother with LS, and his mother without any LS symptoms. Biochemical examination showed normokalemia in the three mutation carriers. The mutation identified was not found in any other family members, 100 hypertensives, or 100 healthy controls. CONCLUSIONS: Our study identified a novel SCNN1G frameshift mutation in a Chinese family with LS, expanding the genetic spectrum of SCNN1G. Genetic testing helped us identify LS with a pathogenic mutation when the genotypes and phenotype were not completely consistent because of the hypokalemia. This case emphasizes that once a proband is diagnosed with LS by genetic testing, family genetic sequencing is necessary for early diagnosis and intervention for other family members, to protect against severe cardiovascular complications.

12.
BMC Ecol ; 19(1): 11, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30845928

RESUMO

The sixth BMC Ecology Image Competition received more than 145 photographs from talented ecologists around the world, showcasing the amazing biodiversity, natural beauty and biological interactions found in nature. In this editorial, we showcase the winning images, as selected by our guest judge, Professor Zhigang Jiang from the Institute of Zoology of the Chinese Academy of Sciences, with help from the journal's editorial board. Enjoy!


Assuntos
Ecologia , Fotografação
14.
Arthritis Res Ther ; 21(1): 31, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670069

RESUMO

BACKGROUND: Childhood Takayasu's arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death. METHODS: An ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis. RESULTS: The median age at c-TA onset was 14 (interquartile range (IQR) 12-16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7-6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30-0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35-23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27-0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69-0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25-0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24-5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares. CONCLUSIONS: This large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressive management. TRIAL REGISTRATION: NCT03199183 , unique protocol ID: 2016-ZX43. June 26, 2017.

15.
Int J Urol ; 26(2): 192-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30362173

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of tadalafil in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction. METHODS: The present phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study was carried out at 40 study centers in the Asia-Pacific region (mainland China, Taiwan and Korea; NCT01937871). Participants were randomized to receive a placebo (n = 361), tadalafil 5 mg (n = 362) or tamsulosin 0.2 mg (n = 185) in a 2:2:1 ratio for 12 weeks. RESULTS: A total of 909 Asian men were randomized into three groups. After 12 weeks of treatment, a statistically significant improvement in least squares mean change from baseline in total International Prostate Symptom Score was observed in the tadalafil versus the placebo group (-5.49 vs -4.08, respectively; P < 0.001). A statistically significant improvement in the change from baseline for the International Index of Erectile Function-Erectile Function domain score, was observed in tadalafil compared with the placebo at 12 weeks (5.24 vs 1.88, respectively; P < 0.001). A significant improvement was observed in the change from baseline in the percentage of "Yes" responses to Sexual Encounter Profile questions 2 and 3 in the tadalafil versus placebo group at 12 weeks (23.87% vs 10.90%; P < 0.001 and 36.62% vs 15.96%; P < 0.001, respectively). Safety results were consistent with the known tadalafil safety profile. CONCLUSIONS: Tadalafil is efficacious and well tolerated in the treatment of Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction.


Assuntos
Disfunção Erétil/tratamento farmacológico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Inibidores da Fosfodiesterase 5/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Tadalafila/administração & dosagem , Idoso , China , Método Duplo-Cego , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Hiperplasia Prostática/complicações , República da Coreia , Índice de Gravidade de Doença , Taiwan , Tansulosina/administração & dosagem , Resultado do Tratamento
17.
Asian J Androl ; 20(6): 587-592, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30004039

RESUMO

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/uso terapêutico , Tadalafila/efeitos adversos , Tadalafila/uso terapêutico , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Inibidores da Fosfodiesterase 5/administração & dosagem , Vigilância de Produtos Comercializados , Estudos Prospectivos , Tadalafila/administração & dosagem , Resultado do Tratamento , Adulto Jovem
18.
Protein Expr Purif ; 149: 7-12, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29655787

RESUMO

The human thyroid peroxidase (hTPO) is an essential enzyme for thyroid hormone biosynthesis and is expressed in thyroid cells. It is an autoantigen against which antibodies are found in the sera of patients with a number of autoimmune thyroid disorders. Overexpression of hTPO has been achieved using the baculovirus expression vector system (BEVS). However, it is produced largely in an aggregated form in the cell lysate fraction, which increases the complexity of protein extraction. In this study, to achieve improved secretory expression of hTPO via BEVS, a truncated recombinant hTPO protein (hTPOt) was engineered by replacing its original signal peptide (SP) in the N-terminal with five heterologous SPs. Our data showed that the SP from the peptidyl-glycine alpha-amidating monooxygenase (PAM), referred to as SPPAM, significantly promoted the secretion of SPPAM-fused hTPOt (p-hTPOt) in High Five cells. Subsequently, we established an optimized scale-up production procedure for p-hTPOt in a 5-L wave-type bioreactor. The secretory p-hTPOt was purified by immobilized metal-chelating affinity chromatography and ion-exchange chromatography, achieving a protein purity of >95%. Finally, the purified p-hTPOt showed high sensitivity and specificity in reactions with positive or negative human serum samples via the double-antigen sandwich method, suggesting potential applications in hTPO-based research and product development.


Assuntos
Autoantígenos/biossíntese , Reatores Biológicos , Iodeto Peroxidase/biossíntese , Proteínas de Ligação ao Ferro/biossíntese , Animais , Autoantígenos/genética , Baculoviridae/metabolismo , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Escherichia coli , Expressão Gênica , Humanos , Iodeto Peroxidase/genética , Proteínas de Ligação ao Ferro/genética , Oxigenases de Função Mista/química , Complexos Multienzimáticos/química , Sinais Direcionadores de Proteínas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Células Sf9/metabolismo , Transdução de Sinais
19.
Oncotarget ; 8(58): 97801-97810, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228652

RESUMO

Objectives: According to the IASLC/ATS/ERS 2011 classification, there are two new conceptions of lung adenocarcinoma, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), which are very early stages of lung adenocarcinoma. This study aimed to analyze clinical features of AIS and MIA and determine the expression profile of PD-L1 in AIS and MIA. Results: In all 274 patients, 77 were diagnosed as AIS and 197 as MIA. We accidentally found 4 patients with recurrence, which were all MIA. The median age of the patients at diagnosis was both 52 years. 71.4% were female in AIS as while as 71.1% in MIA. 36.4% patients were observed with ever symptoms in AIS and 28.9% in MIA. 12.9% and 8.6% had smoking history respectively in AIS an MIA. All AIS and MIA cases were PD-L1 negative. There was significant association between symptoms and more mild progression of nodules in chest CT before surgery. Materials and Methods: We analyzed some clinical features of 274 patients including age, sex, smoking history, family history, surgery, EGFR mutation, ALK, ROS-1, serum CEA level et al. The expression of PD-L1 was evaluated by immunohistochemical analysis in 37 specimens of MIA and 17 specimens of AIS. Conclusions: There are no significant differences between AIS and MIA in clinical features. AIS and MIA almost do not express PD-L1 protein and without any lymph node metastasis. The surgery intervention is supposed to be as small as possible.

20.
Commun Stat Theory Methods ; 46(1): 344-353, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28603337

RESUMO

In clinical trials with repeated measurements, the responses from each subject are measured multiple times during the study period. Two approaches have been widely used to assess the treatment effect, one that compares the rate of change between two groups and the other that tests the time-averaged difference (TAD). While sample size calculations based on comparing the rate of change between two groups have been reported by many investigators, the literature has paid relatively little attention to the sample size estimation for time-averaged difference (TAD) in the presence of heterogeneous correlation structure and missing data in repeated measurement studies. In this study we investigate sample size calculation for the comparison of time-averaged responses between treatment groups in clinical trials with longitudinally observed binary outcomes. The GEE approach is used to derive a closed-form sample size formula, which is flexible enough to account for arbitrary missing patterns and correlation structures. In particular, we demonstrate that the proposed sample size can accommodate a mixture of missing patterns, which is frequently encountered by practitioners in clinical trials. To our knowledge, this is the first study that considers the mixture of missing patterns in sample size calculation. Our simulation shows that the nominal power and type I error are well preserved over a wide range of design parameters. Sample size calculation is illustrated through an example.

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