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1.
Background
We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical).Methods and Findings
De-identified, individual-level administrative records of health service use for the population of Manitoba, Canada (approximately 1.1 million) were examined. From April 1, 1993 to March 31, 1998, patients were identified with a diagnosis of IHD (ICD-9-CM codes). Index events of CABG or PCI were identified from April 1, 1998 to March 31, 2003. Outcomes were depression or dementia after the index event. Patients were followed forward to March 31, 2006 or until censored. Proportional hazards regression analysis was undertaken. Independent variables examined were age, sex, diabetes, hypertension and income quintile, medical management alone for IHD, or intervention by PCI or CABG. Age, sex, diabetes, and presence of hypertension were all strongly associated with the diagnosis of depression and dementia. There was no association with income quintile. Dementia was less frequent with PCI compared to medical management; (HR = 0.65; p = 0.017). CABG did not provide the same protective effect compared to medical management (HR = 0.90; p = 0.372). New diagnosis depression was more frequent with interventional approaches: PCI (n = 626; hazard ratio = 1.25; p = 0.028) and CABG (n = 1124, HR = 1.32; p = 0.0001) than non-interventional patients (n = 34,508). Subsequent CABG was nearly 16-fold higher (p<0.0001) and subsequent PCI was 22-fold higher (p<0.0001) for PCI-managed than CABG-managed patients.Conclusions
Patients managed with PCI had the lowest likelihood of dementia—only 65% of the risk for medical management alone. Both interventional approaches were associated with a higher risk of new diagnosed depression compared to medical management. Long-term myocardial revascularization was superior with CABG. These findings suggest that PCI may confer a long-term protective effect from dementia. The mechanism(s) of dementia protection requires elucidation. 相似文献2.
Introduction
The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.Methods
Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression.Results
The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = −0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold).Conclusion
Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. 相似文献3.
Tripathi SC Matta A Kaur J Grigull J Chauhan SS Thakar A Shukla NK Duggal R Choudhary AR Dattagupta S Sharma MC Ralhan R Siu KW 《PloS one》2011,6(5):e19213
Background
In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Methodology
Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.Results
Our immunohistochemical analysis demonstrated significant overexpression of nuclear PTMA in squamous cell hyperplasia (63.8%), dysplasia (50%) and HNSCC (61%) in comparison with oral normal mucosa (ptrend<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard''s ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.Conclusions
Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease. 相似文献4.
Yuan-Yuan Huang Qiong Yang Si-Wei Zhou Ying Wei Yan-Xian Chen De-Rong Xie Bei Zhang 《PloS one》2013,8(7)
Background
Both chemoradiotherapy and chemotherapy are used in postoperative adjuvant therapy for resected gastric cancer. However, it is controversial whether chemoradiotherapy or chemotherapy is the optimal strategy for patients with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to provide more evidence on the relative benefits of adjuvant therapies in this setting.Methods
We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed meta-analysis to obtain the relative hazards of adjuvant chemoradiotherapy to chemotherapy on efficacy and toxicities.Results
A total of 895 patients from 3 randomized controlled trials were identified for this meta-analysis. All patients were from Asian countries. Our results showed that postoperative chemoradiotherapy significantly improved locoregional recurrence-free survival [LRRFS: hazard ratio (HR) = 0.53, 95% CI = 0.32–0.87, p = 0.01] and disease-free survival (DFS: HR = 0.72, 95% CI = 0.59–0.89, p = 0.002); however, the improvement of distant metastasis recurrence-free survival (DMRFS: HR = 0.86; 95% CI = 0.66–1.11, p = 0.25) and overall survival (OS: HR = 0.79, 95% CI = 0.61–1.03, p = 0.08) were non-significant. The main grade 3 or 4 toxicities were equivalent between the two groups.Conclusion
In non-selected Asian patients with resected gastric cancer who underwent D2 lymphadenectomy, postoperative chemoradiotherapy improved LRRFS and DFS but might not improve OS compared to postoperative chemotherapy. 相似文献5.
Takeshi Nishijima Hiroyuki Gatanaga Hirokazu Komatsu Kunihisa Tsukada Takuro Shimbo Takahiro Aoki Koji Watanabe Ei Kinai Haruhito Honda Junko Tanuma Hirohisa Yazaki Miwako Honda Katsuji Teruya Yoshimi Kikuchi Shinichi Oka 《PloS one》2012,7(1)
Objective
To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART) in low-body weight treatment-naïve patients with HIV infection.Design
We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART.Methods
The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR) from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model.Results
The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152–2.648; p = 0.009) (adjusted HR = 2.080; 95% CI, 1.339–3.232; p<0.001). In subgroup analysis of the patients stratified by intertertile baseline body weight, the effect of tenofovir on renal dysfunction was more evident in patients with lower baseline body weight by multivariate analysis (≤60 kg: adjusted HR = 2.771; 95%CI, 1.494–5.139; p = 0.001) (61–68 kg: adjusted HR = 1.908; 95%CI, 0.764–4.768; p = 0.167) (>68 kg: adjusted HR = 0.997; 95%CI, 0.318–3.121; p = 0.995). The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003).Conclusion
The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight <60 kg treated with tenofovir. 相似文献6.
Background
Hypoxemia is a grave sequel of pneumonia, and an important predictor of a fatal outcome. Pneumonia in the neonatal period is often associated with lack of breast feeding. However, there is no published report on the impact of the cessation of breast feeding in the neonatal period on the development of pneumonia and hypoxemia. The purpose of our study was to assess the impact of non-breast feeding or stopping breast feeding during the neonatal period (henceforth to be referred to as non-breast fed) on clinical features of pneumonia and hypoxemia in 0–6-month-old infants with diarrhea admitted to an urban hospital in Bangladesh.Methods
We prospectively enrolled all infants (n = 107) aged 0 to 6 months who were admitted to the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B) with diarrhea and pneumonia from September 2007 through December 2007.We compared the clinical features of pneumonia and hypoxemia of breast fed infants (n = 34) with those who were non-breast fed (n = 73).Results
The median (inter-quartile range) duration of hypoxemia (hours) in non-breast-feds was longer than breast-fed infants [0.0 (0.0, 12.0) vs. 12.0 (0.0, 21.75); p = 0.021]. After adjusting for potential confounders such as inability to drink, fever, head nodding, cyanosis, grunting respiration, and lower chest wall in drawing, the non-breast-fed infants with pneumonia along with diarrhea had a higher probability of cough (OR 9.09; CI 1.34–61.71; p = 0.024), hypoxemia (OR 3.32; CI 1.23–8.93; p = 0.017), and severe undernutrition (OR 3.42; CI 1.29–9.12; p = 0.014).Conclusions and Significance
Non-breast feeding or cessation of breast feeding during the neonatal period may substantially increase the incidence of severe malnutrition, incidence of cough, and both the incidence and duration of hypoxemia in young infants presenting with pneumonia and diarrhea. The findings emphasize the paramount importance of the continuation of breast feeding in the neonatal period and early infancy. 相似文献7.
Welker MW Reichert D Susser S Sarrazin C Martinez Y Herrmann E Zeuzem S Piiper A Kronenberger B 《PloS one》2012,7(2):e30796
Aim
Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.Patients and Methods
Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.Results
Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).Conclusion
CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis. 相似文献8.
Background
Taxanes have been extensively used as adjuvant chemotherapy for the treatment of early or operable breast cancer, particularly in high risk, node-negative breast cancer. Previous studies, however, have reported inconsistent findings regarding their clinical efficacy and safety. We investigated disease-free survival (DFS), overall survival (OS), and drug-related toxicities of taxanes by a systematic review and meta-analysis.Methodology and Principal Findings
We systematically searched PubMed, EMBASE, the Cochrane Center Register of Controlled Trials, proceedings of major meetings, and reference lists of articles for studies conducted between January 1980 and April 2011. Randomized controlled trials (RCTs) comparing chemotherapy with and without taxanes in the treatment of patients with early-stage or operable breast cancer were eligible for inclusion in our analysis. The primary endpoint was DFS. Nineteen RCTs including 30698 patients were identified, including 8426 recurrence events and 3803 deaths. Taxanes administration yielded a 17% reduction of hazard ratio (HR) for DFS (HR = 0.83, 95% CI 0.79–0.88, p<0.001) and a 17% reduction of HR for OS (HR = 0.83, 95% CI 0.77–0.90, p<0.001). For high risk, node-negative breast cancer, the pooled HR also favoured the taxane-based treatment arm over the taxane-free treatment arm (HR = 0.82, 95% CI 0.77–0.87, p = 0.022). A significantly increased rate of neutropenia, febrile neutropenia, fatigue, diarrhea, stomatitis, and oedema was observed in the taxane-based treatment arm.Conclusions/Significance
Adjuvant chemotherapy with taxanes could reduce the risk of cancer recurrence and death in patients with early or operable breast cancer, although the drug-related toxicities should be balanced. Furthermore, we also demonstrated that patients with high risk, node-negative breast cancer also benefited from taxanes therapy, a result that was not observed in previous studies. 相似文献9.
Objective
Self-rated health is a generic health indicator predicting mortality, many diseases, and need for care. We examined self-rated health as a predictor of subsequent disability retirement, and ill-health and working conditions as potential explanations for the association.Methods
Self-rated health and the covariates were obtained from the Helsinki Health Study baseline mail surveys in 2000–2002 conducted among municipal employees aged 40–60 years (n = 6525). Data for disability retirement events (n = 625) along with diagnoses were linked from the Finnish Centre for Pensions, with a follow-up by the end of 2010. Hazard ratios (HR) and their 95% confidence intervals (CI) were calculated using competing risks models.Results
Less than good self-rated health predicted disability retirement due to all causes among both women (HR = 4.60, 95% CI = 3.84–5.51) and men (HR = 3.83, 95% CI = 2.64–5.56), as well as due to musculoskeletal diseases (HR = 5.17, 95% CI = 4.02–6.66) and mental disorders (HR = 4.80, 95% CI = 3.50–6.59) among women and men pooled. Ill-health and physical working conditions partly explained the found associations, which nevertheless remained after the adjustments. Among the measures of ill-health limiting long-standing illness explained the association most in all-cause disability retirement and disability retirements due to musculoskeletal diseases, whereas common mental disorders explained the association most in disability retirements due to mental health disorders. Among working conditions physical work load and hazardous exposures at work explained the association most, although much less than ill-health.Conclusions
Self-rated health is a strong predictor of disability retirement. This can be partly explained by ill-health and working conditions. Poor self-rated health provides a useful marker for increased risk of work disability and subsequent disability retirement. 相似文献10.
Magbanua MJ Roy R Sosa EV Weinberg V Federman S Mattie MD Hughes-Fulford M Simko J Shinohara K Haqq CM Carroll PR Chan JM 《PloS one》2011,6(9):e24004
Background
Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.Methods
Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.Results
Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001).Conclusions
We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.Trial Registration
ClinicalTrials.gov NCT00402285相似文献11.
12.
Va P Yang WS Nechuta S Chow WH Cai H Yang G Gao S Gao YT Zheng W Shu XO Xiang YB 《PloS one》2011,6(11):e26600
Background
Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality.Methods
We examined the association of marital status with mortality using data from the Shanghai Women''s Health Study (1996–2009) and Shanghai Men''s Health Study (2002–2009), two population-based cohort studies of 74,942 women aged 40–70 years and 61,500 men aged 40–74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI).Results
Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality.Conclusions
Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women. 相似文献13.
Aims
To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Materials and Methods
Information from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Women''s Health Study and Shanghai Men''s Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.Results
There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92–0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80–0.97 for men; HR = 0.91, 0.86–0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96–1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91–1.10 for men; HR = 1.01, 0.96–1.07 for women) with diabetes risk.Conclusions
Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity. 相似文献14.
Objectives
The significance of blood pressure variability (BPV) for cerebral oxygenation in extremely preterm infants has not been explored, though BPV may well be associated with end organ injury. We hypothesized that increased BPV in sick preterm infants, by exceeding the cerebral autoregulatory capacity, is associated with cerebral oxygenation changes which closely follow the blood pressure fluctuations. We assessed the autoregulatory capacity in the early postnatal period, by determining the correlation between BPV (mmHg2) and coherence of mean arterial blood pressure (MABP mmHg) and cerebral oxygenation (tissue oxygenation index, TOI %).Study Design
Thirty-two preterm infants of mean gestational age of 26.3 (±1.5) weeks were studied on the first 3 postnatal days. Spectral analysis (Coherence and transfer-function gain analysis) was used to calculate coherence of MABP and TOI; BPV was quantified using power spectral density of MABP.Results
Overall, maximum Coherence showed a trend for positive correlation with BPV (n = 32, p = 0.06). Infants identified as clinically unstable with documented brain injury (n = 7) had high Coherence values at low BPV. Separate analysis of stable infants (excluding the 7 critically ill infants) revealed a significant association between maximum Coherence and BPV (n = 25, p = 0.006).Conclusions
Fluctuation in cerebral oxygenation is closely associated with increased BPV in preterm infants undergoing intensive care. Moreover, in the critically sick preterm infant, blood pressure-dependent variations in cerebral oxygenation occur even with relatively lower BPV, suggesting they have severely impaired autoregulation, and placing them at greater vulnerability to cerebral injury arising from blood pressure fluctuations. 相似文献15.
Background
Capecitabine is effective and indicated for the salvage treatment of metastatic breast cancer. Therefore, it is essential to evaluate the efficacy of capecitabine in the adjuvant setting. There have been two large randomized studies to determine whether patients with high-risk early breast cancer benefit from the addition of capecitabine to standard chemotherapy, but they have yielded inconsistent results. We first undertook a meta-analysis to evaluate the efficacy of the addition of capecitabine over standard treatment.Methods
PubMed, EBSCO, Web of Science, conference proceedings and key trials were searched from 1998 to 2011. The hazard ratio (HR) was used to evaluate the efficacy of a taxane-anthracycline regimen and a taxane-anthracycline-capecitabine regimen in early breast cancer. All of the data from each study use either fixed-effects or random-effects by Stata.Findings
We found significant improvement in the additional capecitabine arm versus control in disease-free survival (DFS) (HR = 0.83, 95% CI: 0.71–0.98, P = 0.027), overall survival (OS) (HR = 0.71, 95% CI: 0.57–0.88, P = 0.002), distant recurrence (HR = 0.79, 95% CI: 0.66–0.94, P = 0.008) and the death from breast cancer only (HR = 0.65, 95% CI: 0.51–0.83, P = 0.001). Meanwhile, the subgroup analysis revealed that capecitabine improved the DFS in triple negative (HR = 0.71, 95% CI: 0.53–0.96, P = 0.028), hormone receptor negative (HR = 0.73, CI: 0.56–0.94, P = 0.017) and HER2 negative (HR = 0.81, CI: 0.67–0.98, P = 0.034) patients.Conclusion
Due to the synergistic effect of taxane and capecitabine, taxane-anthracycline-capecitabine regimen may effectively improve the efficacy in the adjuvant setting and may be a novel generation of adjuvant chemotherapy regimen. The results of the current meta-analysis support this hypothesis and indicate that taxane-based regimen with capecitabine may be an effective, convenient, and well tolerated regimen in patients with early breast cancer. 相似文献16.
Latka MH Fielding K Gray GE Bekker LG Nchabeleng M Mlisana K Nielson T Roux S Mkhize B Mathebula M Naicker N de Bruyn G Kublin J Churchyard GJ;HVTN Phambili study team 《PloS one》2012,7(4):e31387
Background
HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/“Phambili” vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy.Methods
To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination (“vaccination period”), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy.Results
Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32–1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22–0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21–0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28–1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16–4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59–12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24–5.72)].Conclusions
It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention.Trial Registration
SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725相似文献17.
M Thillai C Eberhardt AM Lewin L Potiphar S Hingley-Wilson S Sridhar J Macintyre OM Kon M Wickremasinghe A Wells ME Weeks D Mitchell A Lalvani 《PloS one》2012,7(7):e38083
Background
The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them.Methods
We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples.Results
We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%).Conclusions
These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli. 相似文献18.
Background
Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.Methods
DN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.Results
The urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = −0.349, p = 0.01).Conclusion
The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN. 相似文献19.
Nishijima T Komatsu H Gatanaga H Aoki T Watanabe K Kinai E Honda H Tanuma J Yazaki H Tsukada K Honda M Teruya K Kikuchi Y Oka S 《PloS one》2011,6(7):e22661
Background
Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight.Methods
In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis.Results
The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m2 decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058).Conclusion
The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir. 相似文献20.
Díez-Padrisa N Aguilar R Machevo S Morais L Nhampossa T O'Callaghan-Gordo C Nhalungo D Menéndez C Roca A Alonso PL Bassat Q 《PloS one》2011,6(8):e24090