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1.
Medicine (Baltimore) ; 98(30): e16524, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348267

RESUMO

Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported.We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy.A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm and plasma HIV ribonucleic acid (RNA) suppressed (<40 IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively.After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change.The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement.DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Hepatite C/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Coinfecção/imunologia , Coinfecção/virologia , Quimioterapia Combinada , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Hemofilia A/imunologia , Hemofilia A/virologia , Hepacivirus , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Imidazóis/uso terapêutico , Interferons/uso terapêutico , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada
2.
Int J Cancer ; 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31107987

RESUMO

Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.

3.
BMJ ; 365: l1207, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944091

RESUMO

OBJECTIVES: To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC. DESIGN: Nationwide, population based, nested case-control study. SETTING: Sweden. PARTICIPANTS: All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks. RESULTS: Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test. CONCLUSIONS: Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.


Assuntos
Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/epidemiologia , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Colo do Útero/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Sistema de Registros , Risco , Comportamento de Redução do Risco , Neoplasias do Colo do Útero/patologia , Adulto Jovem
4.
BMC Infect Dis ; 19(1): 313, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961560

RESUMO

BACKGROUND: Genetic variability and liability to develop drug-resistant mutations are the main characteristics of HIV-1, which can not only increase the risk of antiretroviral treatment (ART) failure, but also can lead to the spread of resistant strains. We aim to investigate the distribution of HIV-1 genotypes and prevalence of pretreatment drug resistance (PDR) in ART-naïve HIV-1 infected patients in Shanghai China. METHODS: A cross-sectional study was performed among the newly diagnosed ART-naive HIV-1 infected patients during the period from January 2017 to November 2017 in Shanghai Public Health Clinical Center. The target fragment of 1316 bp in the pol gene spanning the reverse transcriptase and protease regions was amplified using a nested polymerase chain reaction. HIV-1 genotypes were determined by phylogenetic analysis, and PDR associated mutations were determined according to Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/ ). RESULTS: We successfully amplified pol gene sequences from blood samples of 317 patients, of whom 95.3% were male, and 68.8% were men who have sex with men. The median age was 33 years; and the median CD4 count was 275 cells/µL. The predominant HIV-1 genotype was circulating recombinant form (CRF) 01_AE (53.0%, 168/317), followed by CRF07_BC (29.7%, 94/317), B (7.6%, 24/317), CRF08_BC (1.9%, 6/317), CRF55_01B (1.9%, 6/317), CRF 59_01B (0.9%, 3/317). In addition, 5% (16/317) HIV-1 strains were identified as other subtypes or CRFs/URFs (unique recombinant forms). The overall prevalence of PDR was 17.4% (55/317). PDR frequency to non-nucleoside reverse transcriptase inhibitor (NNRTI, 16.4%) was much higher than that to nucleoside reverse transcriptase inhibitor (NRTI, 4.7%) and protease inhibitor (PI, 0.6%). The most common HIV-1 mutation pattern for NNRTI and NRTI were V179D/E (10.1%, 32/317) and M184 V (2.8%, 9/317), respectively. About half (49.1%, 27/55) of the HIV-1 strains with mutation presented as potential low-level resistant to NNRTI attributed to V179D/E. CONCLUSION: The distribution of HIV-1 genotypes in Shanghai China is diverse and complex. The high prevalence of PDR highlights the significance of baseline HIV-1 drug resistance testing. Non-NNRTI-containing regimen may be the preferred initial therapy for newly diagnosed HIV-1 patients in Shanghai in the absence of PDR test results.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/genética , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Genes pol , Variação Genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Prevalência
5.
BMC Cardiovasc Disord ; 19(1): 40, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770724

RESUMO

BACKGROUND: Structural remodeling is critical to the initiation and maintenance of atrial fibrillation (AF). IGF1, insulin like growth factor 1, has been recognized as contributor to fibrosis. However, the roles and mechanisms of IGF1 in structural remodeling during AF is still unclear. METHODS: We investigated the transcriptional expression profiles of left atria in AF and non-AF rat models by using microarray analysis. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the accuracy. After bioinformatics analysis, IGF1 was selected to explore its effects and mechanisms on atrial fibrosis. The fibroblasts were extracted from atria of rats, and randomly divided into negative control group, mIGF1 overexpression group and mIGF1 silencing group. Then 30 healthy male Wistar rats were randomly divided into negative control group (n = 10), pacing group (n = 10), pacing + mIGF1 silencing viruses group (n = 10). Then the intracardiac electrophysiological examination, qRT-PCR, Western Blotting, masson staining were conducted after IGF1 interfering experiments. RESULTS: A total of 956 differentially expressed transcripts were identified, in which 395 transcripts were down-regulated and 561 transcripts were up-regulated. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. The inhibition of IGF1 function in AF model could ameliorate the inducibility of AF. The IGF1 plays a fibrotic role by activating the PI3K-Akt pathway to increase the expression of CTGF and AT1R. CONCLUSIONS: IGF1 develops vital function in regulating structural remodeling during AF, which could illustrate the mechanism of AF pathogenesis and supply potential targets for its precise treatment.

6.
Prev Med ; 120: 26-33, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30593796

RESUMO

Ten years after its introduction, equity in human papillomavirus (HPV) vaccine uptake remains unattained, not least for the groups at highest risk of cervical cancer. In Sweden, three different delivery modes of the vaccine have been in effect since May 2007. We used this as a natural experiment to investigate girls' HPV vaccine uptake in relation to parental country of birth and socioeconomic characteristics, by mode of delivery. Our nationwide study cohort comprised 689,676 girls born between 1990 and 2003. Data on HPV vaccination of the girls and parental birth/socioeconomic characteristics were retrieved from national registers. We examined the association between girls' vaccine uptake and parental characteristics, stratified by mode of delivery. The cumulative uptake of at least one dose of HPV vaccine was 37%, 48% and 79% for subsidised opportunistic, free-of-charge catch-up outside-school and free-of-charge school-based vaccination, respectively. In the subsidised vaccination, having parents born outside of Sweden, with low education and low family income was strongly associated with lower uptake [HR (95% confidence interval (CI)) = 0.49 (0.48-0.50), 0.32 (0.31-0.33), 0.53 (0.52-0.54), respectively]. The associations were partially reduced in catch-up outside-school, and strongly reduced in school-based vaccination delivery [HR (95% CI) =0.82 (0.81-0.83), 0.92 (0.91-0.94), 0.87 (0.85-0.88), respectively]. Free-of-charge school-based HPV vaccination achieved the highest uptake and displayed the least disparity in country of birth and socioeconomic background of the parents. This appears to be the most effective and equitable delivery mode for reaching high population vaccination coverage, including high-risk groups for cervical cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30346663

RESUMO

Lopinavir (LPV) is a protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infections. Current studies on LPV are mainly focused on Caucasians, and none have investigated the population pharmacokinetics (PPK) of LPV in Chinese population. The present study aimed to develop a PPK model for oral LPV in Chinese adults who are HIV-infected. A total of 460 LPV concentrations from 174 Chinese patients who received LPV/ritonavir (LPV/r) 400/100 mg orally every 12 hours (q12h) were analysed using the non-linear mixed-effects modelling approach. Simulations of the LPV concentration profile were performed with different dosing regimens. A one-compartment model with first-order absorption and elimination process described the data. The estimated apparent clearance (CL/F) and volume of distribution (V/F) (% relative standard error [RSE]) for oral LPV were 5.9 L/h (3%) and 117 L (8%), respectively. Body-weight was identified as a covariate on CL/F. In patients who weighed between 45 and 115 kg and received the standard 400/100 mg q12h regimen, the probability of achieving target trough concentration (Ctrough ) of 1 mg/L was >98% for PI-naïve patients and the probability of achieving target Ctrough of 4 mg/L was <80% for PI-pretreated patients. This is the first population pharmacokinetic study to characterise the PK of LPV in Chinese patients with HIV infection. There were no obvious ethnic differences in the PK of LPV between the Chinese population and Caucasian population. The simulations demonstrated that the standard dosing regimen of 400/100 mg q12h (LPV/r tablets) appears to be sufficient for PI-naïve patients but suboptimal for PI-pretreated patients. Therefore, the regimen of 800/200 mg q12h was recommended for PI-pretreated patients. Further investigation of dosage recommendation could be helpful in optimising LPV therapy for HIV infections.

8.
BMJ Open ; 8(10): e024477, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30282687

RESUMO

OBJECTIVES: To investigate whether cervical screening attendance differs between human papillomavirus (HPV)-vaccinated and unvaccinated women and to investigate potential underlying socioeconomic factors. DESIGN: Prospective cohort using registry linkage of vaccinations, screening invitations, screening attendance and socioeconomic covariates. SETTING: Swedish national HPV vaccination and cervical screening programmes. PARTICIPANTS: All Swedish women born between 1988 and 1991 and invited to screening (n=261 434). OUTCOME MEASURES: All participants were followed for up to 3 years. Screening attendance was compared between HPV-vaccinated and unvaccinated women. HR and 95% CI were estimated using Cox regression. RESULTS: Vaccination age averaged 18.1 years and the coverage for≥1 dose was 13.5%. In HPV-vaccinated women (n=35 460), screening attendance was higher than in unvaccinated women (n=225 974) (74%vs69%, p<0.001). The crude HR of attendance in HPV-vaccinated women was 1.32 (95% CI 1.30 to 1.34). A positive association remained after adjustment for education, income and migration history (HR=1.10, 95% CI 1.09 to 1.12). CONCLUSION: HPV-vaccinated women were more likely to attend screening than unvaccinated women. Yet, the question needs to be reassessed in routinely vaccinated cohorts, since the vaccinated women included here represent a selected group and may be prone to more health-conscious habits.

9.
Emerg Microbes Infect ; 7(1): 113, 2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934497

RESUMO

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4+ T cell count <300/mm3 than in HISs with a CD4+ T cell count >300/mm3 (Shannon index: Median 2.557 vs. 2.981, P = 0.006; Simpson index: Median 0.168 vs. 0.096, P = 0.004). Additionally, the baseline α-diversity indices correlated with CD4+ T cell counts (Shannon index: r = 0.474, P = 0.004; Simpson index: r = -0.467, P = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4+ T cell counts <300/mm3 was significantly restored (Shannon index: Median 2.557 vs. 2.791, P = 0.007; Simpson index: Median 0.168 vs. 0.112, P = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts >300/mm3 (Shannon index: Median 2.981 vs. 2.934, P = 0.179; Simpson index: Median 0.096 vs. 0.119, P = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4+ T cell counts >300/mm3, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.


Assuntos
Contagem de Linfócito CD4 , Microbioma Gastrointestinal , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Biodiversidade , Biomarcadores , Relação CD4-CD8 , Biologia Computacional/métodos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Metagenoma , Metagenômica , RNA Ribossômico 16S/genética , Carga Viral
10.
PLoS One ; 13(1): e0190171, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29320536

RESUMO

BACKGROUND: Cervical screening programs are highly protective for cervical cancer, but only for women attending screening procedure. OBJECTIVE: Identify socio-economic and demographic determinants for non-attendance in cervical screening. METHODS: Design: Population-based case-control study. Setting: Sweden. Population: Source population was all women eligible for screening. Based on complete screening records, two groups of women aged 30-60 were compared. The case group, non-attending women, (N = 314,302) had no smear registered for 6-8 years. The control group (N = 266,706) attended within 90 days of invitation. Main outcome measures: Risk of non-attendance by 9 groups of socioeconomic and demographic variables. Analysis: Unadjusted odds ratios (OR) and OR after adjustment for all variables in logistic regression models were calculated. RESULTS: Women with low disposable family income (adjOR 2.06; 95% confidence interval (CI) 2.01-2.11), with low education (adjOR 1.77; CI 1.73-1.81) and not cohabiting (adjOR 1.47; CI 1.45-1.50) were more likely to not attend cervical screening. Other important factors for non-attendance were being outside the labour force and receiving welfare benefits. Swedish counties are responsible for running screening programs; adjusted OR for non-participation in counties ranged from OR 4.21 (CI 4.06-4.35) to OR 0.54 (CI 0.52-0.57), compared to the reference county. Being born outside Sweden was a risk factor for non-attendance in the unadjusted analysis but this disappeared in certain large groups after adjustment for socioeconomic factors. CONCLUSION: County of residence and socio-economic factors were strongly associated with lower attendance in cervical screening, while being born in another country was of less importance. This indicates considerable potential for improvement of cervical screening attendance in several areas if best practice of routines is adopted.


Assuntos
Detecção Precoce de Câncer/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Fatores Socioeconômicos , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal/psicologia , Adulto , Estudos de Casos e Controles , Demografia , Escolaridade , Emigrantes e Imigrantes , Emprego , Feminino , Humanos , Renda , Programas de Rastreamento , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Suécia/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem
11.
Eur Radiol ; 28(4): 1373-1382, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29124384

RESUMO

OBJECTIVES: To evaluate the performance of computed tomography angiography (CTA) ≥64 slices for detecting coronary in-stent restenosis (ISR) and determine the influence of separate characteristics on diagnostic accuracy. METHODS: We searched the PubMed, EMBASE and Cochrane databases for studies of CTA ≥64 slices in diagnosing ISR. We pooled data on bivariate modelling, and subgroup analysis was also performed. RESULTS: A total of 35 studies involving 4131 stents were included. The pooled positive likelihood ratio (LR+) and the negative likelihood ratio (LR-) were 14.0 and 0.10, for CTA in diagnosis-significant ISR ≥50%. LR+ and LR- were similar between CTA >64 slices versus 64 slices (both P > 0.99). LR- (0.10) was good for ruling out suspected ISR for <3-mm diameter. Time between CTA and stent implantation >6 months did not affect the ability of CTA for the high LR+ (12.3) and the LR- (0.10). Thick-strut stents ≥100 µm or bifurcation stenting demonstrated inferior accuracy, which was unfavourable for stent imaging. CONCLUSIONS: With the high LR+ and LR- of CTA, patients with ISR may be appropriate for non-invasive angiographic follow-up. However, CTA imaging seems unsuitable for patients with characteristics unfavourable for stent imaging, such as thick-strut stents or bifurcation stenting. KEY POINTS: • CTA may provide accurate information on characteristics of in-stent restenosis lesions. • Using CTA, ISR patients may be appropriate for non-invasive angiographic follow-up. • Stent diameter and the number of slices do not influence CTA. • CTA seems unsuitable for patients with thick-strut stents or bifurcation stenting.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Reestenose Coronária/diagnóstico por imagem , Análise de Falha de Equipamento/métodos , Stents , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
12.
Cardiol J ; 25(1): 128-141, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29064534

RESUMO

BACKGROUND: The preventive effects of laboratory personalized antiplatelet therapy (PAPT) strategy in-cluding genetic detection and platelet function testing (PFT) on major adverse cardiac events (MACEs) and bleeding events in coronary artery disease (CAD) patients undergoing stenting has been extensively studied. Despite that, no clear conclusion can be drawn. In this study, a meta-analysis was performed to explore a more precise estimation of the benefits of laboratory PAPT. METHODS: Randomized controlled trials were identified by the use of search databases such as PubMed, Embase, and Cochrane Controlled Trials Register up to May 2017, and the estimates were pooled. RESULTS: Fourteen studies including 9497 patients met the inclusion criteria. The laboratory PAPT reduced MACEs risk (risk ratio [RR] 0.58, 95% confidence interval [CI] 0.42-0.80, p = 0.001), stent thrombosis (RR 0.60, 95% CI 0.41-0.87, p = 0.008) and myocardial infarctions (RR 0.43, 95% CI 0.21-0.88, p = 0.02) compared to the non-PAPT group. No statistically significant difference was observed between the two groups regarding cardiovascular death (RR 0.77, 95% CI 0.51-1.16, p = 0.21), bleeding events (RR 0.96, 95% CI 0.81-1.13, p = 0.59) and ischemic stroke (RR 0.81; 95% CI 0.39-1.66, p = 0.57). The preventive effect on MACEs was more significant in patients with high on-treatment platelet reactivity (RR 0.46; 95% CI 0.27-0.80, p = 0.006). CONCLUSIONS: Coronary artery disease patients after stenting could obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128-141).


Assuntos
Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos
13.
PLoS Med ; 14(10): e1002414, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29065127

RESUMO

BACKGROUND: The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. METHODS AND FINDINGS: Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. CONCLUSIONS: In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Fatores Etários , Idoso , Células Escamosas Atípicas do Colo do Útero/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Teste de Papanicolaou , Modelos de Riscos Proporcionais , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Suécia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
14.
J Mol Cell Cardiol ; 108: 73-85, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28546098

RESUMO

Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 99,843 putative new lncRNAs were identified, in which 1220 differentially expressed transcripts exhibited >2-fold change. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. On the basis of a series of filtering pipelines, one lncRNA, TCONS_00075467, was selected to explore its effects and mechanisms on electrical remodeling. The atrial effective refractory period was shortened in vivo and the L-type calcium current and action potential duration were decreased in vitro by silencing of TCONS_00075467 with lentiviruses. Besides, the expression of miRNA-328 was negatively correlated with TCONS_00075467. We further demonstrated that TCONS_00075467 could sponge miRNA-328 in vitro and in vivo to regulate the downstream protein coding gene CACNA1C. In addition, miRNA-328 could partly reverse the effects of TCONS_00075467 on electrical remodeling. In summary, dysregulated lncRNAs may play important roles in modulating electrical remodeling during AF. Our study may facilitate the mechanism studies of lncRNAs in AF pathogenesis and provide potential therapeutic targets for AF.


Assuntos
Fibrilação Atrial/genética , Átrios do Coração/metabolismo , RNA Longo não Codificante/genética , Transcriptoma , Animais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/genética , Canais de Cálcio Tipo L/genética , Biologia Computacional/métodos , Eletrocardiografia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Átrios do Coração/patologia , Masculino , MicroRNAs/genética , Interferência de RNA , Coelhos
15.
AIDS Res Hum Retroviruses ; 33(2): 164-171, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27832707

RESUMO

Both Caspase 1-induced cell death and Caspase 3-induced cell death were reported to be the causes of CD4+ T cell depletion in HIV infection. We measured by flow cytometry the expression of key proteins associated with pyroptosis (Caspase 1), apoptosis (Caspase 3, Caspase 8, Caspase 9), and immune activation in peripheral T cells. The percentages of CD4+ T cells that expressed Caspase 1 and Caspase 3 were significantly higher in untreated human immunodeficiency virus 1 (HIV-1) patients compared with healthy control (Caspase 1: 19.40% vs. 4.65%, p = .006; Caspase 3: 12.75% vs. 4.18%, p < .001). However, the percentages of Caspase 3 in CD8+ T cells increased significantly, while the percentages of Caspase 1 in CD8+ T cells did not change significantly (Caspase 1: 3.33% vs. 1.99%, p = .821; Caspase 3: 20.35% vs 4.74%, p < .001). The percentages of HLA-DR+ CD38+ CD8+ T cells were positively correlated with those of Caspase 1+ CD4+ T cells, but not with those of Caspase 3+ CD4+ T cells. After highly active antiretroviral therapy, the percentages of Caspase 1, but not of Caspase 3, -expressing CD4+ T cells decreased to a level comparable with those of healthy controls (Caspase 1: 6.05% vs. 4.65%, p = .514; Caspase 3: 9.67% vs. 4.18%, p < .001). Our study indicated that CD4+ T cells experience both pyroptosis and apoptosis, while CD8+ T cells undergo only apoptosis in HIV-1 infection. Pyroptosis, but not apoptosis, in CD4+ T cells may be inhibited by effective antiretroviral therapy.


Assuntos
Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/química , Caspase 1/análise , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Adulto , Antígenos CD/análise , Linfócitos T CD8-Positivos/química , Caspase 3/análise , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
J Cardiovasc Pharmacol Ther ; 22(2): 142-152, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27512080

RESUMO

BACKGROUND: Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACEs). This has been a highly controversial topic for years. DESIGN: The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs is associated with increased risk of MACEs than with clopidogrel alone in patients with coronary artery disease. METHODS: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs) were combined using a random-effects model. RESULTS: Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn't. CONCLUSION: The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated with significantly increased MACE in patients coadministered with clopidogrel.

17.
Am J Obstet Gynecol ; 216(1): 48.e1-48.e15, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27457115

RESUMO

BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. OBJECTIVE: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period (n = 2,466,671). Follow-up of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy (incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.


Assuntos
Adenocarcinoma/epidemiologia , Assistência ao Convalescente/métodos , Células Escamosas Atípicas do Colo do Útero/patologia , Carcinoma Adenoescamoso/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Colposcopia/estatística & dados numéricos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Biópsia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Teste de Papanicolaou , Distribuição de Poisson , Análise de Regressão , Lesões Intraepiteliais Escamosas Cervicais/terapia , Suécia/epidemiologia , Esfregaço Vaginal , Adulto Jovem
18.
Medicine (Baltimore) ; 95(21): e3802, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27227959

RESUMO

To investigate the frequency and the spectrum of major opportunistic infections (OIs), evaluate the major clinical factors associated with each specific OI, and identify the risk factors for in-hospital death among HIV patients in East China.A retrospective cohort study was made including all the HIV-infected patients who were admitted for the first time to the Shanghai Public Health Clinical Center during June 1, 2013 to June 1, 2015. The demographic and clinical data were collected. Comparison of continuous variables was analyzed by one-way ANOVA and rank sum test. Person χ test and Fisher exact test were applied to analyze the categorical variables. A Cox proportional hazards regression model was used to determine the risk for the occurrence of in-hospital death.In total, 920 patients were enrolled with age of 41.59 ± 13.36 years and 91% male. Median CD4 was 34 (IQR, 13-94) cells/µL. Among these patients, 94.7% acquired OIs while the rest developed malignancies. Pneumocystis pneumonia and bacterial coinfection (42.1%) was found to be the most common OIs, followed by tuberculosis (31.4%), CMV (20.9%), Cryptococcosis (9.0%), and MAC infection (5.2%). Of the above 5 major OIs, CMV-infected patients had the lowest median CD4 cell count 22.50 (IQR, 7.50-82.00) while the patients with tuberculosis infection had the highest count 61.00 (IQR, 27.00-176.00). In-hospital death rate was 4.2 per 100 person-years among these patients. Of note, admitted patients with 2 types of OIs (2.20, 95% CI 1.39-3.48) and those patients who were 40-year old or older (1.75, 95% CI 1.10-2.78) had a higher risk of such death.Pneumocystis pneumonia and tuberculosis were still the leading causes for the admission of HIV-infected patients in East China, and these patients tended to have very low CD4 cell counts. It is believed that expanding the HIV screening test and pushing the infected ones get ART earlier is required for generating a more successful HIV management strategy.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Contagem de Linfócito CD4 , China/epidemiologia , Coinfecção , Feminino , Infecções por HIV/complicações , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Estudos Retrospectivos , Fatores de Risco , Tuberculose/complicações
19.
BMJ ; 352: i276, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26869597

RESUMO

OBJECTIVES: To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. DESIGN: Nationwide population based cohort study. SETTING: Cancer and population registries in Sweden. PARTICIPANTS: 3,054,328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2,899,968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. MAIN OUTCOME MEASURES: Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. RESULTS: The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. CONCLUSIONS: AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted.


Assuntos
Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Distribuição por Idade , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Suécia/epidemiologia , Esfregaço Vaginal , Adulto Jovem
20.
Biosci Trends ; 10(1): 42-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26911541

RESUMO

When treating HIV-infected patients with hemophilia, adverse drug reactions and interactions and the effect of treatment on bleeding disorders must be considered. Raltegravir is the first HIV integrase inhibitor, but its use in patients with hemophilia is rarely reported. Nine HIV-positive patients with hemophilia were retrospectively studied with a focus on the virological response, changes in the CD4 count, the tendency to bleed, and the response to replacement therapy before and after raltegravir-based antiretroviral therapy (ART). The nine patients were highly treatment-experienced patients and they received raltegravir-based ART for at least nine months. The patients had their own reasons for changing to raltegravir-based ART. During treatment, the CD4 count increased progressively in four patients, with a median absolute increase of 233 cells/mm(3), while the count stabilized in the remaining five patients. Two previous recipients of lopinavir/ritonavir (LPV/r) who failed to respond to lamivudine (3TC) + zidovudine (ZDV) + efavirenz (EFV) had a viral rebound. Genotyping indicated multidrug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). A pattern of resistance to raltegravir was evident, including the primary mutation N155H and the secondary mutation T97A. In the two patients, the tendency to bleed decreased markedly and monthly usage of clotting factor VIII decreased significantly decreased. In the remaining seven patients, the viral load remained < 40 copies/mL, there was no evidence of an increased tendency to bleed, and no evidence of changes in the response to replacement therapy. All of the patients had a stable condition with no signs of disease progression and no serious adverse reactions. Results indicated that Raltegravir-based therapy offered a safe and well-tolerated option for HIV-positive patients with hemophilia.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Adulto , Farmacorresistência Viral/genética , Humanos , Integrases/genética , Pessoa de Meia-Idade , Mutação/genética , Raltegravir Potássico/efeitos adversos , Raltegravir Potássico/farmacologia , Raltegravir Potássico/uso terapêutico , Resultado do Tratamento
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